Dermatopathia Pigmentosa Reticularis

Mendelian MONDO:0007445 Pathograph 17 Show in embeddings browser

Dermatopathia pigmentosa reticularis (DPR) is a very rare autosomal dominant ectodermal dysplasia defined by the triad of generalized reticulate hyperpigmentation that begins at birth or in early childhood and persists for life, diffuse noncicatricial alopecia, and onychodystrophy. Adermatoglyphia, palmoplantar hyperkeratosis, hypohidrosis or hyperhidrosis, heat intolerance, acral nonscarring blisters and mucosal pigmentation are variable associated features. DPR is allelic with Naegeli-Franceschetti-Jadassohn syndrome (NFJS): both are caused by heterozygous nonsense or frameshift variants in the region of KRT14 encoding the nonhelical head (E1/V1) domain, in contrast to the rod-domain KRT14 variants that cause epidermolysis bullosa simplex. Ultrastructural study of affected skin shows increased apoptosis in the KRT14-expressing basal layer, and work on NFJS alleles shows keratin 14 haploinsufficiency with increased keratinocyte susceptibility to TNF-alpha induced apoptosis. The steps from basal-cell apoptosis to the reticulate pigment pattern, hair loss and nail dystrophy are inferred rather than demonstrated.

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1
Inheritance
5
Pathophys.
1
Histopath.
11
Phenotypes
17
Pathograph
1
Genes
1
Variants
3
Medical Actions
2
Differentials
4
References
1
Deep Research
👪

Inheritance

1
Autosomal dominant inheritance HP:0000006
Transmitted as an autosomal dominant trait; a family pedigree established dominant transmission, and heterozygous KRT14 variants segregate with the disease. Associated features vary between patients.
Autosomal dominant inheritance Expressivity: VARIABLE
Show evidence (2 references)
PMID:1303619 SUPPORT Human Clinical
"A family pedigree demonstrates the autosomal dominant inheritance of dermatopathia pigmentosa reticularis."
Pedigree evidence for dominant transmission of DPR.
PMID:16960809 SUPPORT Human Clinical
"Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are two closely related autosomal dominant ectodermal dysplasia syndromes"
States the dominant inheritance of DPR in the gene-identification study.
⚙

Pathophysiology

5
KRT14 Head Domain Truncating Variant
Mechanism confidence: Established
The initiating lesion is a germline heterozygous nonsense or frameshift variant in the part of KRT14 that encodes the nonhelical head (E1/V1) domain, predicted to terminate translation very early. One DPR family and four NFJS families were studied in the gene-identification work, so the DPR-specific evidence rests on a single family. Rod-domain KRT14 variants instead cause epidermolysis bullosa simplex.
KRT14 hgnc:6416 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves KRT14 (hgnc:6416). hgnc:6416 is a gene from the HUGO Gene Nomenclature Committee.
Genetic context KRT14 hgnc:6416 HUGO Gene Nomenclature Committee (hgnc) Relation: this genetic context concerns this gene This genetic context concerns KRT14 (hgnc:6416). hgnc:6416 is a gene from the HUGO Gene Nomenclature Committee. Genomic context: coding sequence allele_type: nonsense or frameshift variant_origin: GERMLINE zygosity: HETEROZYGOUS functional_impact_category: LOSS_OF_FUNCTION
Loss of function is assigned from the haploinsufficiency shown for NFJS head-domain alleles; it has not been tested separately for the DPR allele.
Downstream
Keratin 14 Haploinsufficiency Shown for NFJS head-domain alleles; the DPR allele is assumed to act the same way because it lies in the same region and has the same predicted consequence.
Defective Dermatoglyphic and Sweat Gland Ontogenesis Proposed from the absence of dermatoglyphics and abnormal sweating in carriers; the developmental steps have not been studied.
Diffuse nonscarring alopecia Hair loss is a defining DPR feature in the carriers studied, but no study links KRT14 head-domain loss to a hair-follicle mechanism.
Show evidence (2 references)
PMID:16960809 SUPPORT Human Clinical
"Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families."
Segregation of heterozygous truncating KRT14 variants in the DPR family and four NFJS families.
PMID:16960809 SUPPORT Human Clinical
"NFJS/DPR-associated mutations were found in a region of the gene encoding the nonhelical head (E1/V1) domain and are predicted to result in very early termination of translation."
Places the DPR/NFJS variants in the head domain and distinguishes them from rod-domain EBS variants.
Keratin 14 Haploinsufficiency
Mechanism confidence: Provisional
Head-domain truncating alleles reduce the amount of keratin 14 available to the basal keratinocyte keratin filament network. Demonstrated for NFJS alleles; whether every DPR allele acts purely by haploinsufficiency, rather than through a truncated product, has not been tested.
basal cell of epidermis CL:0002187 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves basal cell of epidermis (CL:0002187). CL:0002187 is a cell type from the Cell Ontology.
KRT14 hgnc:6416 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves KRT14 (hgnc:6416). hgnc:6416 is a gene from the HUGO Gene Nomenclature Committee.
keratin 14 structural constituent of the epidermis GO:0030280 ↓ DECREASED Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased keratin 14 structural constituent of the epidermis, annotated with structural constituent of skin epidermis (GO:0030280). GO:0030280 is a molecular function from the Gene Ontology.
keratin filament GO:0045095 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves keratin filament (GO:0045095). GO:0045095 is a cellular component from the Gene Ontology.
Downstream
Increased Basal Keratinocyte Apoptosis Reduced KRT14 expression increased TNF-alpha induced apoptosis in a keratinocyte cell line, a response blocked by doxycycline.
Show evidence (1 reference)
PMID:18049449 SUPPORT INDIRECT Human Clinical
"Collectively, our results indicate that NFJS results from haploinsufficiency for K14"
Haploinsufficiency is established for NFJS, the allelic disorder; extension to DPR is by inference.
Increased Basal Keratinocyte Apoptosis
Mechanism confidence: Provisional
Electron microscopy of NFJS/DPR patient skin shows increased apoptotic activity in the basal cell layer where KRT14 is expressed. The N-terminal keratin domain is proposed to protect keratinocytes from pro-apoptotic signals such as TNF-alpha; that protective function is supported in cultured keratinocytes, not shown in patient tissue.
basal cell of epidermis CL:0002187 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves basal cell of epidermis (CL:0002187). CL:0002187 is a cell type from the Cell Ontology.
keratinocyte apoptotic process GO:0097283 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased keratinocyte apoptotic process (GO:0097283). GO:0097283 is a biological process from the Gene Ontology. cellular response to tumor necrosis factor GO:0071356 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves cellular response to tumor necrosis factor (GO:0071356). GO:0071356 is a biological process from the Gene Ontology.
Downstream
Basal Layer Degeneration and Pigment Incontinence Basal cell damage would be expected to release melanin into the dermis; DPR biopsies show basal layer degeneration with dermal melanophages, but the link to apoptosis is inferred, not shown in the same tissue.
Onychodystrophy Proposed in case discussion; nail-matrix apoptosis has not been examined.
Palmoplantar hyperkeratosis Proposed in case discussion; the keratoderma mechanism has not been examined.
Show evidence (2 references)
PMID:16960809 SUPPORT Human Clinical
"Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed"
Patient skin shows increased basal-layer apoptosis.
PMID:18049449 SUPPORT In Vitro
"This phenomenon was not observed when cells were cultured in the presence of doxycycline, a known negative regulator of TNF-alpha-dependant pro-apoptotic signaling."
Ties the increased apoptosis to TNF-alpha dependent signaling in the cell model.
Basal Layer Degeneration and Pigment Incontinence
Mechanism confidence: Provisional
Biopsies of reticulate pigmented skin show liquefaction or vacuolar degeneration of the basal layer, increased basal pigmentation and melanin dropped into the papillary dermis within melanophages. The findings are consistent across case reports but are not specific to DPR.
basal cell of epidermis CL:0002187 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves basal cell of epidermis (CL:0002187). CL:0002187 is a cell type from the Cell Ontology. melanophage CL:0002060 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves melanophage (CL:0002060). CL:0002060 is a cell type from the Cell Ontology.
Downstream
Reticulate hyperpigmentation Dermal melanin is the histological substrate of the pigmented lesions; why it forms a reticulate pattern and why it persists for life in DPR, unlike in NFJS, is unexplained.
Show evidence (2 references)
PMID:31008174 SUPPORT Human Clinical
"A biopsy specimen from the reticulate hyperpigmentation on the trunk revealed epidermal atrophy, increased basal layer pigmentation, basal layer degeneration, and the presence of melanophages in dermis."
Primary biopsy of a DPR pigmented lesion.
PMID:23440032 SUPPORT BACKGROUND Human Clinical
"The typical histopathologic picture of DPR shows liquefaction degeneration of the basal layer and dermal pigmentary incontinence."
Summarizes the recurrent histopathology of DPR pigmented skin.
Defective Dermatoglyphic and Sweat Gland Ontogenesis
Mechanism confidence: Hypothetical
Absent dermatoglyphics and abnormal sweating suggest that keratin 14 is needed for epidermal ridge and sweat gland development. Dermal ridges and eccrine sweat pores develop together, which would explain why the two features co-occur. No developmental study in DPR or NFJS tissue exists.
sweat gland development GO:0060792 ⚠ ABNORMAL Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal sweat gland development (GO:0060792). GO:0060792 is a biological process from the Gene Ontology.
Downstream
Adermatoglyphia Inferred from the co-occurrence of absent dermatoglyphics with KRT14 variants.
Hypohidrosis Inferred; sweat gland structure and function have not been measured in DPR carriers.
Show evidence (2 references)
PMID:16960809 SUPPORT INDIRECT Human Clinical
"These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands."
Proposed role inferred from the phenotype of carriers.
PMID:23440032 SUPPORT BACKGROUND Human Clinical
"Embryologic development of dermal ridges occurs in conjunction with the eccrine glands and sweat pores are found on the ridges."
Developmental background linking ridge and sweat gland formation.
✶

Histopathology

1
Basal layer degeneration with dermal melanophages
Reticulate pigmented skin shows basal layer liquefaction or vacuolar degeneration, increased basal pigmentation, pigment incontinence with dermal melanophages and sometimes interface dermatitis. The pattern supports but does not establish the diagnosis.
Show evidence (1 reference)
PMID:36225994 SUPPORT REVIEW SYNTHESIS Human Clinical
"The histopathology of the reticulate pigmentation of DPR is not diagnostic, and the reported histopathological features include mild orthokeratosis, papillomatosis, heavily pigmented epidermis, liquefaction degeneration of the basal layer, dermal pigmentary incontinence, melanophages, interface..."
Summary of reported DPR histopathology and its nondiagnostic nature.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Dermatopathia Pigmentosa Reticularis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

11
Eye 1
Salzmann corneal nodules HP:6001230 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Salzmann nodular degeneration of cornea, annotated with Salzmann corneal nodules (HP:6001230). HP:6001230 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26695611 SUPPORT Human Clinical
"We present an 11 year old young Indian girl with DPR who had Salzmann's nodular degeneration of cornea with moderate dry eye."
Single case report of the corneal finding.
Head and Neck 1
Reticulate pigmentation of oral mucosa HP:0012788 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Oral mucosal pigmentation, annotated with Reticulate pigmentation of oral mucosa (HP:0012788). HP:0012788 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:36225994 SUPPORT Human Clinical
"On mucosal examination, there were hyperpigmented macules on lips, palate, buccal mucosa and glans penis."
Mucosal pigmentation in a single patient.
PMID:37372478 SUPPORT REVIEW SYNTHESIS Human Clinical
"nonscarring blisters on the dorsal sides of the hands and feet, and pigmentation of the oral mucosa can be observed in patients with DPR"
Review listing oral mucosal pigmentation among DPR features.
Integument 8
Reticulate hyperpigmentation Reticular hyperpigmentation HP:0007588 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Generalized reticulate hyperpigmentation, annotated with Reticular hyperpigmentation (HP:0007588). HP:0007588 is a phenotype from the Human Phenotype Ontology.
Show evidence (3 references)
PMID:17958818 SUPPORT Human Clinical
"The reticulate pigmentation occurs at birth or during early childhood."
Onset of the defining pigmentation.
PMID:31008174 SUPPORT Human Clinical
"We report a 24-year-old Iraqi man with diffuse reticulate hyperpigmentation that presented at birth and continues throughout adulthood"
Congenital pigmentation persisting into adulthood in one patient.
PMID:27512211 SUPPORT REVIEW SYNTHESIS Human Clinical
"DPR has been distinguished from NFJS by the lifelong persistence of the skin hyperpigmentation, partial alopecia, and absence of dental anomalies."
Lifelong persistence of pigmentation distinguishes DPR from NFJS.
Diffuse nonscarring alopecia HP:0001596 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Diffuse nonscarring alopecia, annotated with Alopecia (HP:0001596). HP:0001596 is a phenotype from the Human Phenotype Ontology.
Show evidence (3 references)
PMID:1303619 SUPPORT Human Clinical
"Dermatopathia pigmentosa reticularis is a rare heritable disorder consisting of a triad of cutaneous findings including reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy."
Alopecia is part of the diagnostic triad.
PMID:12230514 SUPPORT Human Clinical
"diffuse alopecia is only seen in dermatopathia pigmentosa reticularis"
Alopecia distinguishes DPR from NFJS.
PMID:32995033 SUPPORT Human Clinical
"Based on previous studies, it is the first time that we report a DPR patient with beard alopecia"
Single case extending the alopecia distribution to the beard.
Onychodystrophy Nail dystrophy HP:0008404 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Onychodystrophy, annotated with Nail dystrophy (HP:0008404). HP:0008404 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:1303619 SUPPORT Human Clinical
"Dermatopathia pigmentosa reticularis is a rare heritable disorder consisting of a triad of cutaneous findings including reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy."
Nail dystrophy is part of the diagnostic triad.
PMID:23440032 SUPPORT Human Clinical
"We report a case of a 21 year old woman who had generalized reticulate pigmentation, diffuse noncicatricial alopecia and onychodystrophy of finger and toe nails."
Fingernail and toenail dystrophy in a patient with the full triad.
Adermatoglyphia HP:0007455 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Adermatoglyphia (HP:0007455). HP:0007455 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:16960809 SUPPORT Human Clinical
"clinically share complete absence of dermatoglyphics (fingerprint lines)"
Absent dermatoglyphics is shared by DPR and NFJS.
PMID:2360843 SUPPORT Human Clinical
"Our patient had no fingernail and toenail prints, a striking finding also noted in some, but not all, of the other nine patients."
Variable presence among early reported patients.
Palmoplantar hyperkeratosis HP:0000972 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Palmoplantar hyperkeratosis (HP:0000972). HP:0000972 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:1303619 SUPPORT Human Clinical
"We present a patient with the classic features of the dermatopathia pigmentosa reticularis triad, along with adermatoglyphia, hypohidrosis, and punctate hyperkeratosis of the palms and soles."
Punctate palmoplantar hyperkeratosis in a familial case.
Hypohidrosis HP:0000966 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypohidrosis (HP:0000966). HP:0000966 is a phenotype from the Human Phenotype Ontology.
Sequelae: Heat intolerance
Show evidence (1 reference)
PMID:9164071 SUPPORT Human Clinical
"We present a Korean patient with the typical features of the DPR triad, along with adermatoglyphia, hypohidrosis, and nonscarring blisters on the dorsa of the feet."
Hypohidrosis in a DPR patient.
Hyperhidrosis HP:0000975 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hyperhidrosis (HP:0000975). HP:0000975 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32995033 SUPPORT Human Clinical
"We report the first case from Syria with classical features of the triad along with hyperhidrosis and adermatoglyphia."
Hyperhidrosis in a DPR patient.
Acral nonscarring blisters Acral blistering HP:0031045 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Acral nonscarring blisters, annotated with Acral blistering (HP:0031045). HP:0031045 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:9164071 SUPPORT Human Clinical
"Many other dermatologic findings have been associated with this triad, including adermatoglyphia, hypohidrosis or hyperhidrosis, palmoplantar hyperkeratosis, and nonscarring blisters on the dorsa of the hands and feet."
Acral blisters are a recognized associated feature.
PMID:27512211 SUPPORT Human Clinical
"presented with generalized reticulate pigmentation since birth as well as generalized sweating and recurrent blisters, mainly over the soles"
Recurrent plantar blisters in two siblings.
Metabolism 1
Heat intolerance HP:0002046 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Heat intolerance (HP:0002046). HP:0002046 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31008174 SUPPORT Human Clinical
"These lesions were associated with a lack of dermatoglyphics, hyperhidrosis, and heat intolerance."
Heat intolerance in a DPR patient.
🧬

Genetic Associations

1
KRT14
Gene: KRT14 hgnc:6416 gene page HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is KRT14 (hgnc:6416). hgnc:6416 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE variant_origin: GERMLINE
Show evidence (2 references)
PMID:16960809 SUPPORT Human Clinical
"Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families."
Segregation of KRT14 variants in DPR and NFJS families.
PMID:27512211 SUPPORT REVIEW SYNTHESIS Human Clinical
"DPR results from mutations in the KRT14 gene located on chromosome 17."
Review confirming KRT14 as the DPR gene.
Variants (1)
p.Arg125Cys (R125C)
single nucleotide variant
Recurrent KRT14 rod-domain missense variant, best known as a cause of epidermolysis bullosa simplex, reported in a Malay patient with a DPR diagnosis who had acral blisters but no alopecia. This allele does not fit the head-domain truncation mechanism and the case may represent phenotypic overlap with EBS.
Show evidence (1 reference)
PMID:19040520 SUPPORT Human Clinical
"We report a patient of Malay ancestry with dermatopathia pigmentosa reticularis (DPR) resulting from a recurrent KRT14 p.R125C mutation."
Single-patient report of a rod-domain missense variant with a DPR diagnosis.
💊

Medical Actions

3
Topical minoxidil
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: minoxidil CHEBI:6942 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses minoxidil (CHEBI:6942). CHEBI:6942 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Topical minoxidil 5% improved scalp hair density in single case reports; it was reported ineffective for beard alopecia in another case. No controlled data exist.
Target Phenotypes: Alopecia HP:0001596 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Alopecia (HP:0001596). HP:0001596 is a phenotype from the Human Phenotype Ontology.
Show evidence (3 references)
PMID:36225994 SUPPORT Human Clinical
"While the reticulate pigmentation has not responded, patient reports significant improvement in hair density after 6 months of use of minoxidil."
Single-patient report of improved hair density; pigmentation did not respond to azelaic acid.
PMID:36386069 SUPPORT Human Clinical
"Topical minoxidil led to reversal of scalp alopecia."
A second single-patient report.
PMID:32995033 REFUTE Human Clinical
"Topical minoxidil 5% has not been shown to be effective for beard alopecia."
No benefit for beard alopecia in a third patient.
Topical retinoids and keratolytics
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: topical retinoic acid CHEBI:15367 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses topical retinoic acid, annotated with all-trans-retinoic acid (CHEBI:15367). CHEBI:15367 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Symptomatic management of palmoplantar hyperkeratosis with topical retinoic acid and keratolytics. Reported as management in case reports, without outcome data.
Target Phenotypes: Palmoplantar hyperkeratosis HP:0000972 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Palmoplantar hyperkeratosis (HP:0000972). HP:0000972 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:23440032 SUPPORT Human Clinical
"For hyperkeratosis, topical retinoic acids and keratolytics may be beneficial."
Suggested symptomatic treatment; no measured outcome.
PMID:26695611 SUPPORT Human Clinical
"She was put on topical retinoic acid for the hyperkeratosis"
Use of topical retinoic acid for hyperkeratosis in one patient; response not reported.
Heat avoidance and hydration
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Platform: Behavioral / lifestyle
Patients with abnormal sweating are advised to limit heat exposure and strenuous activity and to stay hydrated, as for other ectodermal dysplasias.
Target Phenotypes: Heat intolerance HP:0002046 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Heat intolerance (HP:0002046). HP:0002046 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42541155 SUPPORT Human Clinical
"Similar to other ectodermal dysplasias, patients with DPR and NFJS should restrict heat exposure and ensure sufficient hydration8"
Expert advice in a case report, not a tested intervention.
📊

Prevalence

1
Published literature
Cases In Literature Ultra Rare
No population-based rate exists. Case reports count fewer than about twenty to twenty-one published patients; these are counts of reports, not of affected people.
Show evidence (2 references)
PMID:27512211 SUPPORT REVIEW SYNTHESIS Human Clinical
"Reviewing the literature revealed that <20 cases of true DPR have been reported in the literature."
Literature count of published DPR cases, the only occurrence measure available.
PMID:32995033 SUPPORT BACKGROUND Human Clinical
"DPR has been acknowledged as a very rare disorder with approximately 21 reported cases among the regions of America, Europe and Asia"
A later count of published cases, consistent with an ultra-rare disorder.
🔀

Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from Dermatopathia Pigmentosa Reticularis:

Naegeli-Franceschetti-Jadassohn syndrome Not Yet Curated MONDO:0008059
Overlapping Features Allelic KRT14 head-domain disorder sharing adermatoglyphia, reticulate pigmentation, keratoderma and abnormal sweating; overlapping presentations occur within one family.
Distinguishing Features
  • Pigmentation in NFJS classically fades after puberty, whereas in DPR it persists for life.
  • Diffuse nonscarring alopecia favors DPR; dental enamel defects favor NFJS.
Show evidence (2 references)
PMID:31008174 SUPPORT BACKGROUND Human Clinical
"The clinical features of NFJS include dental abnormalities and, in many cases, the hyperpigmentation fades or disappears after puberty or in adulthood; in addition, nonscarring alopecia is not a feature of NFJS."
Clinical features used to separate NFJS from DPR.
PMID:42541155 SUPPORT Human Clinical
"We report a rare case involving 2 siblings: case 1, a 24-year-old male with a diagnosis of DPR, and case 2, his 28-year-old sister demonstrating features of an overlap ectodermal dysplasia syndrome."
Overlap within one sibship shows the boundary is not absolute.
Dyskeratosis congenita MONDO:0015780
Overlapping Features Reticulate pigmentation with nail dystrophy, but with oral leukoplakia and bone marrow failure.
Distinguishing Features
  • Oral leukoplakia, bone marrow dysfunction and cancer predisposition point to dyskeratosis congenita.
Show evidence (1 reference)
PMID:23440032 SUPPORT BACKGROUND Human Clinical
"Reticulate hyperpigmentation, mucosal leukoplakia, bone marrow dysfunction, cytogenetic instability, and a predisposition to malignancy are characteristic of DKC."
Features that distinguish dyskeratosis congenita.
{ }

Source YAML

click to show 
name: Dermatopathia Pigmentosa Reticularis
creation_date: "2026-10-09T12:00:00Z"
description: >-
  Dermatopathia pigmentosa reticularis (DPR) is a very rare autosomal dominant ectodermal dysplasia defined by
  the triad of generalized reticulate hyperpigmentation that begins at birth or in early childhood and persists
  for life, diffuse noncicatricial alopecia, and onychodystrophy. Adermatoglyphia, palmoplantar hyperkeratosis,
  hypohidrosis or hyperhidrosis, heat intolerance, acral nonscarring blisters and mucosal pigmentation are
  variable associated features. DPR is allelic with Naegeli-Franceschetti-Jadassohn syndrome (NFJS): both are
  caused by heterozygous nonsense or frameshift variants in the region of KRT14 encoding the nonhelical head
  (E1/V1) domain, in contrast to the rod-domain KRT14 variants that cause epidermolysis bullosa simplex.
  Ultrastructural study of affected skin shows increased apoptosis in the KRT14-expressing basal layer, and work
  on NFJS alleles shows keratin 14 haploinsufficiency with increased keratinocyte susceptibility to TNF-alpha
  induced apoptosis. The steps from basal-cell apoptosis to the reticulate pigment pattern, hair loss and nail
  dystrophy are inferred rather than demonstrated.
category: Mendelian
disease_term:
  preferred_term: Dermatopathia Pigmentosa Reticularis
  term:
    id: MONDO:0007445
    label: dermatopathia pigmentosa reticularis
synonyms:
- DPR
notes: >-
  No disease-specific GeneReviews chapter exists for DPR; the epidermolysis bullosa simplex chapter covers
  rod-domain KRT14 disease and is not a baseline for this entry. DPR is curated separately from
  Naegeli-Franceschetti-Jadassohn syndrome (MONDO:0008059) because MONDO, OMIM and the clinical literature keep
  them as distinct diagnoses that differ in pigment persistence, alopecia and dental involvement, although
  a single family can carry both labels with the same KRT14 frameshift variant and the two may share one
  pathograph. Molecular confirmation in DPR rests on few families, and most mechanistic evidence comes from
  NFJS alleles; nodes that rely on NFJS data say so. Not cited as evidence, because no quotable text was
  retrieved on the fetches made for this entry: PMID:30968399 (intrafamilial NFJS/DPR overlap with the same
  KRT14 frameshift), PMID:39106435 (molecularly confirmed DPR family initially suspected to be dyskeratosis
  congenita), PMID:20180888 (a KRT14 missense variant with a DPR/NFJS phenotype) and PMID:7591467 (etretinate
  for DPR-associated palmoplantar keratoderma).
prevalence:
- population: Published literature
  measure_type: CASES_IN_LITERATURE
  prevalence_class: ULTRA_RARE
  notes: >-
    No population-based rate exists. Case reports count fewer than about twenty to twenty-one published
    patients; these are counts of reports, not of affected people.
  evidence:
  - reference: PMID:27512211
    reference_title: "Dermatopathia Pigmentosa Reticularis: Report of a New Cases and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Reviewing the literature revealed that <20 cases of true DPR have been reported in the literature."
    explanation: Literature count of published DPR cases, the only occurrence measure available.
  - reference: PMID:32995033
    reference_title: "Dermatopathia pigmentosa reticularis with beard alopecia: first report from Syria."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "DPR has been acknowledged as a very rare disorder with approximately 21 reported cases among the regions of America, Europe and Asia"
    explanation: A later count of published cases, consistent with an ultra-rare disorder.
inheritance:
- name: Autosomal dominant inheritance
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  expressivity: VARIABLE
  description: >-
    Transmitted as an autosomal dominant trait; a family pedigree established dominant transmission, and
    heterozygous KRT14 variants segregate with the disease. Associated features vary between patients.
  evidence:
  - reference: PMID:1303619
    reference_title: "Dermatopathia pigmentosa reticularis: a report of a family demonstrating autosomal dominant inheritance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A family pedigree demonstrates the autosomal dominant inheritance of dermatopathia pigmentosa reticularis."
    explanation: Pedigree evidence for dominant transmission of DPR.
  - reference: PMID:16960809
    reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are two closely related autosomal dominant ectodermal dysplasia syndromes"
    explanation: States the dominant inheritance of DPR in the gene-identification study.
pathophysiology:
- name: KRT14 Head Domain Truncating Variant
  biological_scale: MOLECULAR
  mechanism_confidence: ESTABLISHED
  description: >-
    The initiating lesion is a germline heterozygous nonsense or frameshift variant in the part of KRT14 that
    encodes the nonhelical head (E1/V1) domain, predicted to terminate translation very early. One DPR family
    and four NFJS families were studied in the gene-identification work, so the DPR-specific evidence rests on a
    single family. Rod-domain KRT14 variants instead cause epidermolysis bullosa simplex.
  genes:
  - preferred_term: KRT14
    term:
      id: hgnc:6416
      label: KRT14
  genetic_context:
    genes:
    - preferred_term: KRT14
      term:
        id: hgnc:6416
        label: KRT14
    allele_type: nonsense or frameshift
    genomic_contexts:
    - coding sequence
    variant_origin: GERMLINE
    zygosity: HETEROZYGOUS
    functional_impact_category: LOSS_OF_FUNCTION
    notes: >-
      Loss of function is assigned from the haploinsufficiency shown for NFJS head-domain alleles; it has not
      been tested separately for the DPR allele.
  evidence:
  - reference: PMID:16960809
    reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families."
    explanation: Segregation of heterozygous truncating KRT14 variants in the DPR family and four NFJS families.
  - reference: PMID:16960809
    reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "NFJS/DPR-associated mutations were found in a region of the gene encoding the nonhelical head (E1/V1) domain and are predicted to result in very early termination of translation."
    explanation: Places the DPR/NFJS variants in the head domain and distinguishes them from rod-domain EBS variants.
  downstream:
  - target: Keratin 14 Haploinsufficiency
    causal_link_type: DIRECT
    description: >-
      Shown for NFJS head-domain alleles; the DPR allele is assumed to act the same way because it lies in the
      same region and has the same predicted consequence.
    evidence:
    - reference: PMID:18049449
      reference_title: KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "we further expand the spectrum of NFJS-causing mutations and demonstrate that these mutations result in haploinsufficiency for keratin 14 (K14)."
      explanation: Haploinsufficiency was demonstrated for NFJS alleles of the same class; applying it to DPR is an inference across allelic diagnoses.
  - target: Defective Dermatoglyphic and Sweat Gland Ontogenesis
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Proposed from the absence of dermatoglyphics and abnormal sweating in carriers; the developmental steps
      have not been studied.
    evidence:
    - reference: PMID:16960809
      reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands."
      explanation: The authors' inference from the genotype-phenotype data, not a developmental study.
  - target: Diffuse nonscarring alopecia
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Hair loss is a defining DPR feature in the carriers studied, but no study links KRT14 head-domain loss to
      a hair-follicle mechanism.
    evidence:
    - reference: PMID:31008174
      reference_title: "Dermatopathia pigmentosa reticularis: A report of a case with delayed onset alopecia and onychodystrophy."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: BACKGROUND
      directness: INDIRECT
      snippet: "Dermatopathia pigmentosa reticularis (DPR) is an extremely rare autosomal dominant ectodermal dysplasia that occurs because of mutations in KRT14."
      explanation: Places the hair phenotype of DPR downstream of KRT14 mutation without naming the intermediate steps.
- name: Keratin 14 Haploinsufficiency
  biological_scale: MOLECULAR
  mechanism_confidence: PROVISIONAL
  description: >-
    Head-domain truncating alleles reduce the amount of keratin 14 available to the basal keratinocyte keratin
    filament network. Demonstrated for NFJS alleles; whether every DPR allele acts purely by haploinsufficiency,
    rather than through a truncated product, has not been tested.
  genes:
  - preferred_term: KRT14
    term:
      id: hgnc:6416
      label: KRT14
  molecular_functions:
  - preferred_term: keratin 14 structural constituent of the epidermis
    modifier: DECREASED
    term:
      id: GO:0030280
      label: structural constituent of skin epidermis
  cellular_components:
  - preferred_term: keratin filament
    term:
      id: GO:0045095
      label: keratin filament
  cell_types:
  - preferred_term: basal cell of epidermis
    term:
      id: CL:0002187
      label: basal cell of epidermis
  evidence:
  - reference: PMID:18049449
    reference_title: KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    snippet: "Collectively, our results indicate that NFJS results from haploinsufficiency for K14"
    explanation: Haploinsufficiency is established for NFJS, the allelic disorder; extension to DPR is by inference.
  downstream:
  - target: Increased Basal Keratinocyte Apoptosis
    causal_link_type: DIRECT
    description: >-
      Reduced KRT14 expression increased TNF-alpha induced apoptosis in a keratinocyte cell line, a response
      blocked by doxycycline.
    evidence:
    - reference: PMID:18049449
      reference_title: KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "Using a HaCaT cell-based assay, we found that decreased KRT14 expression is associated with increased susceptibility to TNF-alpha-induced apoptosis."
      explanation: Knock-down of KRT14 in HaCaT keratinocytes increases TNF-alpha induced apoptosis.
- name: Increased Basal Keratinocyte Apoptosis
  biological_scale: CELLULAR
  mechanism_confidence: PROVISIONAL
  description: >-
    Electron microscopy of NFJS/DPR patient skin shows increased apoptotic activity in the basal cell layer
    where KRT14 is expressed. The N-terminal keratin domain is proposed to protect keratinocytes from
    pro-apoptotic signals such as TNF-alpha; that protective function is supported in cultured keratinocytes,
    not shown in patient tissue.
  cell_types:
  - preferred_term: basal cell of epidermis
    term:
      id: CL:0002187
      label: basal cell of epidermis
  biological_processes:
  - preferred_term: keratinocyte apoptotic process
    modifier: INCREASED
    term:
      id: GO:0097283
      label: keratinocyte apoptotic process
  - preferred_term: cellular response to tumor necrosis factor
    term:
      id: GO:0071356
      label: cellular response to tumor necrosis factor
  evidence:
  - reference: PMID:16960809
    reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed"
    explanation: Patient skin shows increased basal-layer apoptosis.
  - reference: PMID:18049449
    reference_title: KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "This phenomenon was not observed when cells were cultured in the presence of doxycycline, a known negative regulator of TNF-alpha-dependant pro-apoptotic signaling."
    explanation: Ties the increased apoptosis to TNF-alpha dependent signaling in the cell model.
  downstream:
  - target: Basal Layer Degeneration and Pigment Incontinence
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Basal cell damage would be expected to release melanin into the dermis; DPR biopsies show basal layer
      degeneration with dermal melanophages, but the link to apoptosis is inferred, not shown in the same tissue.
    evidence:
    - reference: PMID:37372478
      reference_title: Inherited Reticulate Pigmentary Disorders.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: REVIEW_SYNTHESIS
      directness: INDIRECT
      snippet: "This suggests that apoptosis plays a significant role in the development of DPR, providing evidence for its pathogenesis"
      explanation: A review's interpretation of the basal-layer apoptosis finding as the pathogenic step in DPR.
  - target: Onychodystrophy
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Proposed in case discussion; nail-matrix apoptosis has not been examined.
    evidence:
    - reference: PMID:42541155
      reference_title: Dermatopathia pigmentosa reticularis and overlap syndrome in siblings-A rare case report.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: BACKGROUND
      directness: INDIRECT
      snippet: "A deficit in keratin 14 elevates the probability of epidermal cells going through apoptosis, resulting in the skin and nail anomalies characteristic of NFJS/DPR."
      explanation: Authors' synthesis linking keratin 14-related apoptosis to the nail anomalies; not a nail-specific experiment.
  - target: Palmoplantar hyperkeratosis
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Proposed in case discussion; the keratoderma mechanism has not been examined.
    evidence:
    - reference: PMID:42541155
      reference_title: Dermatopathia pigmentosa reticularis and overlap syndrome in siblings-A rare case report.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: BACKGROUND
      directness: INDIRECT
      snippet: "A deficit in keratin 14 elevates the probability of epidermal cells going through apoptosis, resulting in the skin and nail anomalies characteristic of NFJS/DPR."
      explanation: Authors' synthesis attributing the skin anomalies, including keratoderma, to keratinocyte apoptosis.
- name: Basal Layer Degeneration and Pigment Incontinence
  biological_scale: TISSUE
  mechanism_confidence: PROVISIONAL
  description: >-
    Biopsies of reticulate pigmented skin show liquefaction or vacuolar degeneration of the basal layer,
    increased basal pigmentation and melanin dropped into the papillary dermis within melanophages. The
    findings are consistent across case reports but are not specific to DPR.
  cell_types:
  - preferred_term: basal cell of epidermis
    term:
      id: CL:0002187
      label: basal cell of epidermis
  - preferred_term: melanophage
    term:
      id: CL:0002060
      label: melanophage
  evidence:
  - reference: PMID:31008174
    reference_title: "Dermatopathia pigmentosa reticularis: A report of a case with delayed onset alopecia and onychodystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A biopsy specimen from the reticulate hyperpigmentation on the trunk revealed epidermal atrophy, increased basal layer pigmentation, basal layer degeneration, and the presence of melanophages in dermis."
    explanation: Primary biopsy of a DPR pigmented lesion.
  - reference: PMID:23440032
    reference_title: "Dermatopathia pigmentosa reticularis: A rare reticulate pigmentary disorder."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "The typical histopathologic picture of DPR shows liquefaction degeneration of the basal layer and dermal pigmentary incontinence."
    explanation: Summarizes the recurrent histopathology of DPR pigmented skin.
  downstream:
  - target: Reticulate hyperpigmentation
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Dermal melanin is the histological substrate of the pigmented lesions; why it forms a reticulate pattern
      and why it persists for life in DPR, unlike in NFJS, is unexplained.
    evidence:
    - reference: PMID:27512211
      reference_title: "Dermatopathia Pigmentosa Reticularis: Report of a New Cases and Literature Review."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Histopathology showed hyperkeratosis, basal layer hyperpigmentation with cytoplasmic vacuolization, interface dermatitis, and scattered melanophages within the reticular dermis"
      explanation: Biopsies of the pigmented lesions in two siblings show basal vacuolization with dermal melanophages, the tissue correlate of the pigmentation.
- name: Defective Dermatoglyphic and Sweat Gland Ontogenesis
  biological_scale: TISSUE
  mechanism_confidence: HYPOTHETICAL
  description: >-
    Absent dermatoglyphics and abnormal sweating suggest that keratin 14 is needed for epidermal ridge and sweat
    gland development. Dermal ridges and eccrine sweat pores develop together, which would explain why the two
    features co-occur. No developmental study in DPR or NFJS tissue exists.
  biological_processes:
  - preferred_term: sweat gland development
    modifier: ABNORMAL
    term:
      id: GO:0060792
      label: sweat gland development
  evidence:
  - reference: PMID:16960809
    reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    snippet: "These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands."
    explanation: Proposed role inferred from the phenotype of carriers.
  - reference: PMID:23440032
    reference_title: "Dermatopathia pigmentosa reticularis: A rare reticulate pigmentary disorder."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "Embryologic development of dermal ridges occurs in conjunction with the eccrine glands and sweat pores are found on the ridges."
    explanation: Developmental background linking ridge and sweat gland formation.
  downstream:
  - target: Adermatoglyphia
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Inferred from the co-occurrence of absent dermatoglyphics with KRT14 variants.
    evidence:
    - reference: PMID:16960809
      reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands."
      explanation: Links the dermatoglyphic defect to a developmental role of KRT14.
  - target: Hypohidrosis
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Inferred; sweat gland structure and function have not been measured in DPR carriers.
    evidence:
    - reference: PMID:16960809
      reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands."
      explanation: Links abnormal sweating to a proposed developmental role of KRT14 in sweat glands.
phenotypes:
- name: Reticulate hyperpigmentation
  category: Dermatologic
  diagnostic: true
  description: >-
    Generalized reticulate brown pigmentation, often predominantly truncal, beginning at birth or in early
    childhood and persisting for life. Lifelong persistence is the main clinical feature separating DPR from
    NFJS, where pigmentation classically fades after puberty.
  phenotype_term:
    preferred_term: Generalized reticulate hyperpigmentation
    term:
      id: HP:0007588
      label: Reticular hyperpigmentation
  evidence:
  - reference: PMID:17958818
    reference_title: Dermatopathia pigmentosa reticularis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The reticulate pigmentation occurs at birth or during early childhood."
    explanation: Onset of the defining pigmentation.
  - reference: PMID:31008174
    reference_title: "Dermatopathia pigmentosa reticularis: A report of a case with delayed onset alopecia and onychodystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We report a 24-year-old Iraqi man with diffuse reticulate hyperpigmentation that presented at birth and continues throughout adulthood"
    explanation: Congenital pigmentation persisting into adulthood in one patient.
  - reference: PMID:27512211
    reference_title: "Dermatopathia Pigmentosa Reticularis: Report of a New Cases and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "DPR has been distinguished from NFJS by the lifelong persistence of the skin hyperpigmentation, partial alopecia, and absence of dental anomalies."
    explanation: Lifelong persistence of pigmentation distinguishes DPR from NFJS.
- name: Diffuse nonscarring alopecia
  category: Dermatologic
  diagnostic: true
  description: >-
    Diffuse noncicatricial hair loss of the scalp, sometimes with eyebrow, axillary or beard involvement;
    onset may be delayed until puberty or adulthood.
  phenotype_term:
    preferred_term: Diffuse nonscarring alopecia
    term:
      id: HP:0001596
      label: Alopecia
  evidence:
  - reference: PMID:1303619
    reference_title: "Dermatopathia pigmentosa reticularis: a report of a family demonstrating autosomal dominant inheritance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Dermatopathia pigmentosa reticularis is a rare heritable disorder consisting of a triad of cutaneous findings including reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy."
    explanation: Alopecia is part of the diagnostic triad.
  - reference: PMID:12230514
    reference_title: Refined mapping of Naegeli-Franceschetti- Jadassohn syndrome to a 6 cM interval on chromosome 17q11.2-q21 and investigation of candidate genes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "diffuse alopecia is only seen in dermatopathia pigmentosa reticularis"
    explanation: Alopecia distinguishes DPR from NFJS.
  - reference: PMID:32995033
    reference_title: "Dermatopathia pigmentosa reticularis with beard alopecia: first report from Syria."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Based on previous studies, it is the first time that we report a DPR patient with beard alopecia"
    explanation: Single case extending the alopecia distribution to the beard.
- name: Onychodystrophy
  category: Dermatologic
  diagnostic: true
  description: Dystrophic finger and toe nails, part of the diagnostic triad; onset may be delayed.
  phenotype_term:
    preferred_term: Onychodystrophy
    term:
      id: HP:0008404
      label: Nail dystrophy
  evidence:
  - reference: PMID:1303619
    reference_title: "Dermatopathia pigmentosa reticularis: a report of a family demonstrating autosomal dominant inheritance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Dermatopathia pigmentosa reticularis is a rare heritable disorder consisting of a triad of cutaneous findings including reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy."
    explanation: Nail dystrophy is part of the diagnostic triad.
  - reference: PMID:23440032
    reference_title: "Dermatopathia pigmentosa reticularis: A rare reticulate pigmentary disorder."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We report a case of a 21 year old woman who had generalized reticulate pigmentation, diffuse noncicatricial alopecia and onychodystrophy of finger and toe nails."
    explanation: Fingernail and toenail dystrophy in a patient with the full triad.
- name: Adermatoglyphia
  category: Dermatologic
  description: >-
    Absent or hypoplastic fingerprint ridges, shared with NFJS. Reported in many but not all DPR patients.
  phenotype_term:
    preferred_term: Adermatoglyphia
    term:
      id: HP:0007455
      label: Adermatoglyphia
  evidence:
  - reference: PMID:16960809
    reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "clinically share complete absence of dermatoglyphics (fingerprint lines)"
    explanation: Absent dermatoglyphics is shared by DPR and NFJS.
  - reference: PMID:2360843
    reference_title: Dermatopathia pigmentosa reticularis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our patient had no fingernail and toenail prints, a striking finding also noted in some, but not all, of the other nine patients."
    explanation: Variable presence among early reported patients.
- name: Palmoplantar hyperkeratosis
  category: Dermatologic
  description: Diffuse or punctate thickening of the palms and soles, a variable associated feature.
  phenotype_term:
    preferred_term: Palmoplantar hyperkeratosis
    term:
      id: HP:0000972
      label: Palmoplantar hyperkeratosis
  evidence:
  - reference: PMID:1303619
    reference_title: "Dermatopathia pigmentosa reticularis: a report of a family demonstrating autosomal dominant inheritance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We present a patient with the classic features of the dermatopathia pigmentosa reticularis triad, along with adermatoglyphia, hypohidrosis, and punctate hyperkeratosis of the palms and soles."
    explanation: Punctate palmoplantar hyperkeratosis in a familial case.
- name: Hypohidrosis
  category: Dermatologic
  description: Reduced sweating; some patients instead report hyperhidrosis, and some sweat normally.
  phenotype_term:
    preferred_term: Hypohidrosis
    term:
      id: HP:0000966
      label: Hypohidrosis
  evidence:
  - reference: PMID:9164071
    reference_title: A case of dermatopathia pigmentosa reticularis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We present a Korean patient with the typical features of the DPR triad, along with adermatoglyphia, hypohidrosis, and nonscarring blisters on the dorsa of the feet."
    explanation: Hypohidrosis in a DPR patient.
  sequelae:
  - target: Heat intolerance
    description: Reduced sweating limits heat dissipation.
    evidence:
    - reference: PMID:12230514
      reference_title: Refined mapping of Naegeli-Franceschetti- Jadassohn syndrome to a 6 cM interval on chromosome 17q11.2-q21 and investigation of candidate genes.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      snippet: "autosomal dominant ectodermal dysplasias characterized by the absence of dermatoglyphics, reticulate hyper pigmentation of the skin, hypohidrosis, and heat intolerance"
      explanation: Hypohidrosis and heat intolerance are listed together as shared NFJS/DPR features; the causal link is physiological inference.
- name: Hyperhidrosis
  category: Dermatologic
  description: Increased sweating reported in some DPR patients in place of hypohidrosis.
  phenotype_term:
    preferred_term: Hyperhidrosis
    term:
      id: HP:0000975
      label: Hyperhidrosis
  evidence:
  - reference: PMID:32995033
    reference_title: "Dermatopathia pigmentosa reticularis with beard alopecia: first report from Syria."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We report the first case from Syria with classical features of the triad along with hyperhidrosis and adermatoglyphia."
    explanation: Hyperhidrosis in a DPR patient.
- name: Heat intolerance
  category: Constitutional
  description: Heat intolerance accompanying abnormal sweating.
  phenotype_term:
    preferred_term: Heat intolerance
    term:
      id: HP:0002046
      label: Heat intolerance
  evidence:
  - reference: PMID:31008174
    reference_title: "Dermatopathia pigmentosa reticularis: A report of a case with delayed onset alopecia and onychodystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "These lesions were associated with a lack of dermatoglyphics, hyperhidrosis, and heat intolerance."
    explanation: Heat intolerance in a DPR patient.
- name: Acral nonscarring blisters
  category: Dermatologic
  description: Transient, self-healing nonscarring blisters on the dorsa of the hands and feet or soles in some patients.
  phenotype_term:
    preferred_term: Acral nonscarring blisters
    term:
      id: HP:0031045
      label: Acral blistering
  evidence:
  - reference: PMID:9164071
    reference_title: A case of dermatopathia pigmentosa reticularis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Many other dermatologic findings have been associated with this triad, including adermatoglyphia, hypohidrosis or hyperhidrosis, palmoplantar hyperkeratosis, and nonscarring blisters on the dorsa of the hands and feet."
    explanation: Acral blisters are a recognized associated feature.
  - reference: PMID:27512211
    reference_title: "Dermatopathia Pigmentosa Reticularis: Report of a New Cases and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "presented with generalized reticulate pigmentation since birth as well as generalized sweating and recurrent blisters, mainly over the soles"
    explanation: Recurrent plantar blisters in two siblings.
- name: Reticulate pigmentation of oral mucosa
  category: Dermatologic
  description: Pigmented macules of the oral or sublingual mucosa in some patients; others have normal mucosa.
  phenotype_term:
    preferred_term: Oral mucosal pigmentation
    term:
      id: HP:0012788
      label: Reticulate pigmentation of oral mucosa
  evidence:
  - reference: PMID:36225994
    reference_title: "Dermatopathia Pigmentosa Reticularis with Addisonian Pigmentation: Atypical Presentation of a Rare Case."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On mucosal examination, there were hyperpigmented macules on lips, palate, buccal mucosa and glans penis."
    explanation: Mucosal pigmentation in a single patient.
  - reference: PMID:37372478
    reference_title: Inherited Reticulate Pigmentary Disorders.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "nonscarring blisters on the dorsal sides of the hands and feet, and pigmentation of the oral mucosa can be observed in patients with DPR"
    explanation: Review listing oral mucosal pigmentation among DPR features.
- name: Salzmann corneal nodules
  category: Ophthalmologic
  description: >-
    Corneal involvement, including fine punctate superficial corneal spots and Salzmann nodular degeneration,
    is reported in a few cases only; an eye abnormality is not expected in every patient.
  phenotype_term:
    preferred_term: Salzmann nodular degeneration of cornea
    term:
      id: HP:6001230
      label: Salzmann corneal nodules
  evidence:
  - reference: PMID:26695611
    reference_title: "Dermatopathia Pigmentosa Reticularis with Salzmann's nodular degeneration of cornea: A rare association."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We present an 11 year old young Indian girl with DPR who had Salzmann's nodular degeneration of cornea with moderate dry eye."
    explanation: Single case report of the corneal finding.
histopathology:
- name: Basal layer degeneration with dermal melanophages
  description: >-
    Reticulate pigmented skin shows basal layer liquefaction or vacuolar degeneration, increased basal
    pigmentation, pigment incontinence with dermal melanophages and sometimes interface dermatitis. The pattern
    supports but does not establish the diagnosis.
  notes: >-
    No finding term is bound: HP:0034572 Pigment incontinence sits under abnormal skin pigmentation rather than
    the abnormal cell morphology or NCIT histopathology branches this slot admits.
  evidence:
  - reference: PMID:36225994
    reference_title: "Dermatopathia Pigmentosa Reticularis with Addisonian Pigmentation: Atypical Presentation of a Rare Case."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "The histopathology of the reticulate pigmentation of DPR is not diagnostic, and the reported histopathological features include mild orthokeratosis, papillomatosis, heavily pigmented epidermis, liquefaction degeneration of the basal layer, dermal pigmentary incontinence, melanophages, interface dermatitis, and sparse, superficial perivascular inflammations."
    explanation: Summary of reported DPR histopathology and its nondiagnostic nature.
genetic:
- name: KRT14
  gene_term:
    preferred_term: KRT14
    term:
      id: hgnc:6416
      label: KRT14
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  notes: >-
    DPR/NFJS alleles are heterozygous nonsense or frameshift variants in the head (E1/V1) domain-encoding region,
    acting by haploinsufficiency as shown for NFJS. They differ from the dominant-negative rod-domain missense
    variants that cause epidermolysis bullosa simplex (kb/disorders/Epidermolysis_Bullosa_Simplex.yaml). The
    recurrent rod-domain variant p.R125C has also been reported in a patient diagnosed with DPR, so the
    head-domain rule describes the molecularly characterized families rather than every published case. No
    ClinGen gene-disease validity classification is recorded here.
  variants:
  - name: p.Arg125Cys (R125C)
    description: >-
      Recurrent KRT14 rod-domain missense variant, best known as a cause of epidermolysis bullosa simplex,
      reported in a Malay patient with a DPR diagnosis who had acral blisters but no alopecia. This allele does
      not fit the head-domain truncation mechanism and the case may represent phenotypic overlap with EBS.
    variant_type: single nucleotide variant
    evidence:
    - reference: PMID:19040520
      reference_title: A case of dermatopathia pigmentosa reticularis with wiry scalp hair and digital fibromatosis resulting from a recurrent KRT14 mutation.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "We report a patient of Malay ancestry with dermatopathia pigmentosa reticularis (DPR) resulting from a recurrent KRT14 p.R125C mutation."
      explanation: Single-patient report of a rod-domain missense variant with a DPR diagnosis.
  evidence:
  - reference: PMID:16960809
    reference_title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families."
    explanation: Segregation of KRT14 variants in DPR and NFJS families.
  - reference: PMID:27512211
    reference_title: "Dermatopathia Pigmentosa Reticularis: Report of a New Cases and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "DPR results from mutations in the KRT14 gene located on chromosome 17."
    explanation: Review confirming KRT14 as the DPR gene.
treatments:
- name: Topical minoxidil
  description: >-
    Topical minoxidil 5% improved scalp hair density in single case reports; it was reported ineffective for
    beard alopecia in another case. No controlled data exist.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: minoxidil
      term:
        id: CHEBI:6942
        label: minoxidil
  target_phenotypes:
  - preferred_term: Alopecia
    term:
      id: HP:0001596
      label: Alopecia
  evidence:
  - reference: PMID:36225994
    reference_title: "Dermatopathia Pigmentosa Reticularis with Addisonian Pigmentation: Atypical Presentation of a Rare Case."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "While the reticulate pigmentation has not responded, patient reports significant improvement in hair density after 6 months of use of minoxidil."
    explanation: Single-patient report of improved hair density; pigmentation did not respond to azelaic acid.
  - reference: PMID:36386069
    reference_title: Dermoscopy of Dermatopathia Pigmentosa Reticularis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Topical minoxidil led to reversal of scalp alopecia."
    explanation: A second single-patient report.
  - reference: PMID:32995033
    reference_title: "Dermatopathia pigmentosa reticularis with beard alopecia: first report from Syria."
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: "Topical minoxidil 5% has not been shown to be effective for beard alopecia."
    explanation: No benefit for beard alopecia in a third patient.
- name: Topical retinoids and keratolytics
  description: >-
    Symptomatic management of palmoplantar hyperkeratosis with topical retinoic acid and keratolytics. Reported
    as management in case reports, without outcome data.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: topical retinoic acid
      term:
        id: CHEBI:15367
        label: all-trans-retinoic acid
  target_phenotypes:
  - preferred_term: Palmoplantar hyperkeratosis
    term:
      id: HP:0000972
      label: Palmoplantar hyperkeratosis
  evidence:
  - reference: PMID:23440032
    reference_title: "Dermatopathia pigmentosa reticularis: A rare reticulate pigmentary disorder."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "For hyperkeratosis, topical retinoic acids and keratolytics may be beneficial."
    explanation: Suggested symptomatic treatment; no measured outcome.
  - reference: PMID:26695611
    reference_title: "Dermatopathia Pigmentosa Reticularis with Salzmann's nodular degeneration of cornea: A rare association."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She was put on topical retinoic acid for the hyperkeratosis"
    explanation: Use of topical retinoic acid for hyperkeratosis in one patient; response not reported.
- name: Heat avoidance and hydration
  description: >-
    Patients with abnormal sweating are advised to limit heat exposure and strenuous activity and to stay
    hydrated, as for other ectodermal dysplasias.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  target_phenotypes:
  - preferred_term: Heat intolerance
    term:
      id: HP:0002046
      label: Heat intolerance
  evidence:
  - reference: PMID:42541155
    reference_title: Dermatopathia pigmentosa reticularis and overlap syndrome in siblings-A rare case report.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Similar to other ectodermal dysplasias, patients with DPR and NFJS should restrict heat exposure and ensure sufficient hydration8"
    explanation: Expert advice in a case report, not a tested intervention.
differential_diagnoses:
- name: Naegeli-Franceschetti-Jadassohn syndrome
  disease_term:
    preferred_term: Naegeli-Franceschetti-Jadassohn syndrome
    term:
      id: MONDO:0008059
      label: Naegeli-Franceschetti-Jadassohn syndrome
  description: >-
    Allelic KRT14 head-domain disorder sharing adermatoglyphia, reticulate pigmentation, keratoderma and abnormal
    sweating; overlapping presentations occur within one family.
  distinguishing_features:
  - Pigmentation in NFJS classically fades after puberty, whereas in DPR it persists for life.
  - Diffuse nonscarring alopecia favors DPR; dental enamel defects favor NFJS.
  evidence:
  - reference: PMID:31008174
    reference_title: "Dermatopathia pigmentosa reticularis: A report of a case with delayed onset alopecia and onychodystrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "The clinical features of NFJS include dental abnormalities and, in many cases, the hyperpigmentation fades or disappears after puberty or in adulthood; in addition, nonscarring alopecia is not a feature of NFJS."
    explanation: Clinical features used to separate NFJS from DPR.
  - reference: PMID:42541155
    reference_title: Dermatopathia pigmentosa reticularis and overlap syndrome in siblings-A rare case report.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We report a rare case involving 2 siblings: case 1, a 24-year-old male with a diagnosis of DPR, and case 2, his 28-year-old sister demonstrating features of an overlap ectodermal dysplasia syndrome."
    explanation: Overlap within one sibship shows the boundary is not absolute.
- name: Dyskeratosis congenita
  disease_term:
    preferred_term: Dyskeratosis congenita
    term:
      id: MONDO:0015780
      label: dyskeratosis congenita
  description: Reticulate pigmentation with nail dystrophy, but with oral leukoplakia and bone marrow failure.
  distinguishing_features:
  - Oral leukoplakia, bone marrow dysfunction and cancer predisposition point to dyskeratosis congenita.
  evidence:
  - reference: PMID:23440032
    reference_title: "Dermatopathia pigmentosa reticularis: A rare reticulate pigmentary disorder."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "Reticulate hyperpigmentation, mucosal leukoplakia, bone marrow dysfunction, cytogenetic instability, and a predisposition to malignancy are characteristic of DKC."
    explanation: Features that distinguish dyskeratosis congenita.
references:
- reference: PMID:30968399
  title: "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: intrafamilial overlap of phenotypes in patients with the same KRT14 frameshift variant."
- reference: PMID:39106435
  title: "A case of dermatopathia pigmentosa reticularis masquerading as dyskeratosis congenita: the importance of nailing the correct diagnosis."
- reference: PMID:20180888
  title: A missense mutation in KRT14 causing a dermatopathia pigmentosa reticularis/Naegeli-Franceschetti-Jadassohn phenotype.
- reference: PMID:7591467
  title: "Palmoplantar keratoderma associated with dermatopathia pigmentosa reticularis: successful treatment with etretinate."
📚

References & Deep Research

References

4
PMID:30968399
Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: intrafamilial overlap of phenotypes in patients with the same KRT14 frameshift variant.
No top-level findings curated for this source.
PMID:39106435
A case of dermatopathia pigmentosa reticularis masquerading as dyskeratosis congenita: the importance of nailing the correct diagnosis.
No top-level findings curated for this source.
PMID:20180888
A missense mutation in KRT14 causing a dermatopathia pigmentosa reticularis/Naegeli-Franceschetti-Jadassohn phenotype.
No top-level findings curated for this source.
PMID:7591467
Palmoplantar keratoderma associated with dermatopathia pigmentosa reticularis: successful treatment with etretinate.
No top-level findings curated for this source.

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Dermatopathia_Pigmentosa_Reticularis · 2026-10-09T21:19:20Z · View source

Created the DPR entry (MONDO:0007445) from the Perplexity deep-research report research/Dermatopathia_Pigmentosa_Reticularis-deep-research-perplexity.md, which passed just preflight-dr (KRT14 mentioned 28 times; OMIM 125595 matches MONDO). The report's reference validation resolved 20/20 identifiers and flagged needs_review for two off-topic PMC records: PMC6440173 is a DPR case report (PMID:30983613) and PMC5672609 an acral reticulate pigmentary disorder review; neither was needed as evidence. Further DPR literature was found by PubMed esearch ("dermatopathia pigmentosa reticularis", 42 hits) and fetched with just fetch-reference. Lump/split: DPR is curated as its own entry, not as an NFJS/DPR spectrum with subtypes. MONDO (MONDO:0007445 vs MONDO:0008059), OMIM and the case literature keep two diagnoses, distinguished by lifelong versus fading pigmentation, alopecia in DPR and dental defects in NFJS. The mechanism is plausibly shared (both caused by heterozygous KRT14 head-domain nonsense/frameshift variants, PMID:16960809), but molecular evidence for DPR rests on one family in that study and the haploinsufficiency and TNF-alpha apoptosis data are from NFJS alleles (PMID:18049449), so the evidence does not clearly show one conserved pathograph that differs only in phenotype. The NFJS stub is left in place for separate curation; a future grouping or lump can revisit this once NFJS is curated. Pathograph: KRT14 head-domain truncating variant -> keratin 14 haploinsufficiency (PROVISIONAL, NFJS-derived) -> increased basal keratinocyte apoptosis (patient ultrastructure + HaCaT TNF-alpha assay) -> basal layer degeneration and pigment incontinence -> reticulate hyperpigmentation; a hypothetical developmental branch to adermatoglyphia and hypohidrosis; case-discussion edges to nail dystrophy and keratoderma. A rod-domain p.R125C DPR case (PMID:19040520) is recorded as a variant that does not fit the head-domain mechanism. Not quotable on the fetches made (content_type unavailable after --force retry): PMID:30968399, PMID:39106435, PMID:20180888, PMID:7591467; listed under references with no evidence. No disease-specific GeneReviews chapter (just check-genereviews: NO_CHAPTER). Validation: just validate, count-verified-snippets (56/56), validate-terms, check-entity-refs, check-causal-targets, check-genereviews and validate-disorders run on the file.

Perplexity ▸
Dermatopathia pigmentosa reticularis: disease-characteristics research report
sonar-deep-research 59 citations 2026-10-09T21:02:16.437472

Dermatopathia pigmentosa reticularis: disease-characteristics research report

Dermatopathia pigmentosa reticularis (DPR; MONDO:0007445) is an exceptionally rare, autosomal-dominant ectodermal dysplasia associated with heterozygous KRT14 variants. Its characteristic clinical combination is persistent reticulate skin hyperpigmentation, nonscarring alopecia, and nail dystrophy. Absence of fingerprints, palmoplantar keratoderma, and abnormal sweating are additional clues. DPR and Naegeli–Franceschetti–Jadassohn syndrome (NFJS) are closely overlapping KRT14-associated phenotypes; a family can show features of both. The evidence base consists mainly of pedigrees, individual case reports, pathology, and a related-syndrome cell experiment—not a prospective natural-history cohort. [52][21][81][65]

Evidence convention: “Human clinical” denotes observations in affected people; “in vitro” denotes cell experiments; “mouse” denotes genetically altered mice. An ontology term marked suggested is a useful annotation, not evidence that its biological process has been experimentally demonstrated in DPR.

1. Disease information

Characteristic Disease-level entry
Definition A genetic disorder of ectoderm-derived skin and appendages, recognized clinically by lifelong reticulate hyperpigmentation, diffuse nonscarring alopecia, and onychodystrophy. [52]
Identifiers MONDO:0007445; OMIM:125595; ORPHA:86920; ICD-10: Q82.4; ICD-11: LD27.0Y; MeSH: C535374; UMLS/MedGen concept: C0406778; MedGen UID: 98037; SNOMED CT: 239088003. The ICD codes are mapped categories, not necessarily DPR-exclusive diagnostic codes. [52][47]
Names Dermatopathia pigmentosa reticularis; DPR. NFJS/DPR denotes the overlapping allelic spectrum, not an exact synonym for the narrower DPR phenotype. [47][81]
Data provenance This is an aggregated disease-level report drawing on curated resources and published, identifiable case or family observations. It is not derived from an individual’s EHR or a population registry. [47][136][21]

Primary genetic evidence: Lugassy and colleagues studied one DPR family and four NFJS families. Their abstract states, “Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families.” Human pedigree and biopsy study; published online 25 August 2006, PMID 16960809, DOI 10.1086/507792, article URL. [21]

2. Etiology: causes, risks, protection, and environment

Factor Finding and interpretation
Established cause Heterozygous, very-early truncating KRT14 variants affecting the keratin-14 nonhelical head region cause the NFJS/DPR spectrum. They alter a keratin network important in basal keratinocytes; the exact reason one carrier has a DPR rather than an NFJS presentation remains unresolved. Human clinical and molecular evidence. [21][81]
Principal risk factor A pathogenic familial variant: an affected heterozygous parent has a 50% chance per pregnancy of transmitting the variant, although the child’s precise phenotype cannot be predicted reliably from that probability. [47][65]
Other genetic risk or modifiers Intra-family phenotypic overlap despite the same frameshift variant demonstrates variable expression; no validated human DPR modifier gene, susceptibility locus, or polygenic score was established in the reviewed evidence. Keratin 16 rescue in mice is an experimental compensation result, not proof that human KRT16 protects against DPR. [65][338]
Environmental causes or susceptibility No toxin, diet, occupation, smoking habit, infection, or pathogen is established as a cause. Heat can aggravate discomfort when sweating is impaired; mechanical stress may aggravate acral skin fragility. These are symptom modifiers, not demonstrated determinants of whether a carrier develops DPR. [52][21]
Protective variants or exposures None established for preventing disease occurrence. Hydration and heat avoidance address consequences of impaired sweating; they do not correct the inherited cause. [252]
Gene–environment interaction An in-vitro, related-NFJS experiment found greater apoptosis after exposure to the inflammatory signal TNF-α when KRT14 expression was reduced. This supports a plausible cellular stress interaction, not an epidemiologically established TNF-α exposure risk for DPR. [web:18049449]

3. Phenotypes, timing, frequency, and impact

Frequency caution: The classical triad describes the DPR phenotype, but there are no defensible population-derived percentages for its individual findings. HPO-linked listings provide terms without usable DPR-specific frequencies; the appended “30” on one aggregator’s labels must not be interpreted as 30%. One 2019 review counted 21 published DPR patients, underscoring the small and selected evidence base. [185][136][65]

Phenotype and type Suggested HPO term Onset, course, and severity Reported frequency and potential impact
Generalized or truncal reticular hyperpigmentation; clinical sign HP:0007588 Birth or early childhood; may spread initially, then characteristically persists throughout life. Extent varies. Defining feature; percentage unavailable. Visible pigmentation can affect appearance and psychosocial well-being, but a DPR-specific quality-of-life effect size is unavailable. [52][76][185]
Nonscarring scalp alopecia, sometimes involving eyebrows or other hair; clinical sign HP:0002293 (alopecia of scalp); HP:0001596 (broader alopecia) Childhood onward; can progressively thin. Usually described as diffuse or partial. Part of classical triad; percentage unavailable. Appearance-related impact is plausible, not quantified. [52][76][97]
Onychodystrophy—brittle, short, thickened or otherwise malformed nails; clinical sign HP:0008404 Childhood; degree and progression vary. A molecularly confirmed family showed hypertrophic nails, subungual hyperkeratosis, and onycholysis. Part of triad; percentage unavailable. May interfere with nail care or manual tasks; no measured DPR-specific disability estimate. [52][81]
Adermatoglyphia, absent or poorly developed fingerprints; physical manifestation HP:0007455 Congenital/developmental; persistent. Variable; percentage unavailable. May complicate fingerprint identification; functional burden has not been quantified in DPR. [21][76][185]
Palmoplantar hyperkeratosis/keratoderma; clinical sign HP:0000972 Childhood, variable thickening; may include pressure-related calluses. Variable; percentage unavailable. Severe thickening can cause discomfort, an individual-care consideration rather than a measured cohort outcome. [52][185]
Hypohidrosis or, less often, hyperhidrosis; symptom/sign HP:0000966 for hypohidrosis; assign a hyperhidrosis term separately if present Developmental, variable; reduced sweating may be accompanied by heat intolerance. Variable; percentage unavailable. Affected individuals may need heat-exposure precautions. [52][252][185]
Acral nonscarring blistering; clinical sign Suggested: an HPO skin-blistering term, to be checked against the patient’s distribution Can occur during the first years of life; not universal. Occasional; percentage unavailable. Blisters can affect comfort and skin integrity. [52][65]
Reticulate oral-mucosal pigmentation; clinical sign HP:0012788 Timing and severity poorly characterized. Reported, not obligatory; percentage unavailable. A 2023 clinical case described buccal and tongue pigmentation. [185][76]
Abnormal conjunctiva morphology or other ocular finding; clinical sign HP:0000502 Insufficient data to specify typical onset or severity. Listed in phenotype resources; frequency unknown. Do not assume an eye abnormality in every patient. [185][136]

The 2023 case report provides a useful single-patient, not frequency, example: a 22-year-old man had pigmentation from birth, alopecia, nail dystrophy, and absent dermatoglyphics, while his teeth and sweating were normal. Pigment International 2023, 10(3):172–178; article URL; no PMID was supplied by the journal page. [76] No DPR-specific EQ-5D, SF-36, PROMIS, or comparable numerical quality-of-life results were identified in these sources.

4. Genetic and molecular information

Gene or variant Classification and origin Evidence and interpretation
KRT14; HGNC:6416, NCBI Gene 3861, OMIM gene 148066, 17q21.2; protein UniProt P02533 Established causal gene for the allelic DPR/NFJS spectrum. Encodes type-I keratin 14, which partners with keratin 5 in the basal epithelial intermediate-filament network. Most convincingly DPR/NFJS-associated reported changes are heterozygous early stop-gain or frameshift variants; other KRT14 variant classes can cause different disorders, notably epidermolysis bullosa simplex (EBS). [48][53][21]
NM_000526.5:c.54C>A; p.(Cys18Ter), historically C18X Germline, heterozygous; the original DPR pedigree established segregation. ClinVar’s DPR-specific submission calls it pathogenic, but its current overall germline aggregate is uncertain significance because another submission disagrees. Do not flatten the conflicting ClinVar classifications into an unqualified ACMG consensus. Original DPR-family evidence: PMID 16960809. ClinVar Variation ID 14626. Its displayed 1000 Genomes global minor-allele frequency is 0.00040; ClinVar flags gnomAD frequency at this position as unreliable, so no dependable gnomAD frequency should be asserted. [21][web:14626]
NM_000526.5:c.19C>T; p.(Gln7Ter), historically Q7X Germline, heterozygous; ClinVar pathogenic for NFJS, Variation ID 66333; also identified in a clinically DPR-affected 2024 family. Same variant across overlapping labels illustrates why sequence alone need not distinguish DPR from NFJS. ClinVar displays gnomAD frequency approximately 0.00001, with one heterozygote and no homozygotes in the cited dataset. 2024 case: PMID 39106435, published online 6 August 2024, DOI 10.1093/ced/llae310, article URL. [web:66333][81]
KRT14 c.17delG, early frameshift Germline, heterozygous; reported in an NFJS family, not the original family labeled DPR. It and the two early nonsense changes segregated with phenotype in the original five-family study. The paper did not specify a modern reference-transcript accession for its original “17delG” notation; avoid assigning an unverified modern HGVS protein consequence. [21]

These are the directly pertinent early variants, not an exhaustive list of KRT14 variation. In particular, an aggregator’s other KRT14 missense records should not be interpreted as proven causal variants for the DPR phenotype merely because they appear under a broadly associated gene or condition. [185][21]

Molecular interpretation: Early truncation is established at the DNA level. Reduced functional K14—haploinsufficiency—is supported by experiments in NFJS-derived research, but a 2024 DPR report explicitly notes conflicting evidence about making haploinsufficiency the complete explanation. Early mutant transcripts may escape complete nonsense-mediated decay, and an alternative downstream translation product was proposed; a dominant-negative contribution has not been conclusively excluded for every variant. No DPR-specific modifier, epigenetic signature, causative chromosomal rearrangement, somatic driver, or reliable variant-based severity predictor is established. A chromosome 1q21.1–q21.2 duplication detected in the 2024 proband was considered relevant to separate neurodevelopmental findings, not the explanation for his DPR skin phenotype. [21][web:18049449][81]

5. Environmental and infectious information

DPR is not classified as an infectious or exposure-induced disease. No causative bacteria, virus, fungus, parasite, pollutant, radiation exposure, occupational exposure, dietary pattern, smoking pattern, or alcohol exposure is established. Heat exposure matters clinically when sweating is reduced; it should be recorded as a potential symptom aggravator, not a cause of the KRT14 variant. No DPR-specific protective lifestyle intervention or validated gene–environment risk estimate is available. [52][21][252]

6. Mechanism and pathophysiology

Ordered causal chain

  1. A germline heterozygous early stop-gain or frameshift in KRT14 leads to a prematurely interrupted keratin-14 coding sequence in the NFJS/DPR spectrum. Demonstrated in human families. [21]
  2. The altered sequence leads to reduced effective K14 protein or altered production of a short/head-deficient product. Reduced K14 is experimentally supported for NFJS; the precise contribution of transcript decay versus alternative products in all DPR variants remains unresolved. [web:18049449][21][81]
  3. Disrupted K14–K5 filament function leads to altered structural resilience and stress responses in basal keratinocytes. Filament abnormalities were observed in affected human skin; assigning every downstream effect specifically to DPR rather than the shared NFJS/DPR spectrum is partly inferred. [21][53]
  4. One branch: reduced keratinocyte protection against pro-apoptotic signals leads to increased basal-cell apoptosis. Human ultrastructure supports increased apoptosis; reducing KRT14 increased TNF-α-induced apoptosis in an NFJS-related HaCaT-cell assay. Extrapolation of that cell response to every DPR lesion is inferred. [21][web:18049449]
  5. Pigmentary branch: basal-layer damage and cell loss lead to pigment incontinence and dermal melanophages; these findings are proposed to contribute to persistent reticulate hyperpigmentation. The histology is observed; the complete mechanism generating its netlike distribution is not demonstrated. [21][76][122]
  6. Developmental/appendage branch: altered basal-epithelial development and maintenance lead to abnormal dermatoglyphics, sweating, hair, nails, and palmoplantar keratinization. These associations are observed; the precise cell-by-cell developmental sequence is inferred. [21][52]

The landmark abstract states: “Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed.” Human pathology, PMID 16960809. The mechanistic experiment’s abstract reports, “decreased KRT14 expression is associated with increased susceptibility to TNF-alpha-induced apoptosis.” In-vitro HaCaT study addressing NFJS, PMID 18049449, published online 29 November 2007 in Journal of Investigative Dermatology 2008, DOI 10.1038/sj.jid.5701187, article URL. Neither quote proves a distinct TNF-α-driven disease pathway in every person with DPR. [21][web:18049449]

Mechanistic annotation Defensible knowledge-base entry
Upstream protein and process K14–K5 intermediate-filament organization; suggested GO:0045109 (intermediate filament organization), GO:0045095 (keratin filament; cellular component), and GO:0005882 (intermediate filament; cellular component). [53][285]
Downstream process Increased apoptotic susceptibility; suggested GO:0006915 (apoptotic process). Pigment incontinence and altered epithelial differentiation are downstream observations or interpretations, not proof of a named Wnt, MAPK, PI3K–AKT, or mTOR cascade in DPR. [21][web:18049449]
Cells Primary: basal epidermal keratinocyte CL:0000312; suggested basal-cell annotation CL:0000646. Melanocytes CL:0000148 contribute pigment; their being the primary mutant target is not demonstrated. Sweat-gland myoepithelial cell CL:0000185 is a relevant suggested cell type, not a proven exclusive target. [21][292][301]
Molecular-profiling limits Patient-skin ultrastructure and targeted RNA/protein work are available; no validated DPR-specific transcriptomic, proteomic, metabolomic, lipidomic, single-cell, spatial-transcriptomic, multi-omics, or CRISPR-screen signature was established by the cited DPR studies. Do not infer an enzyme deficiency, metabolic biomarker, autoimmunity, or disease-specific epigenetic change. [21][web:18049449][81]

7. Anatomical structures affected

Level Affected structures and suggested ontology terms
Organ and body system Primarily the integumentary system: skin UBERON:0002097, nails UBERON:0001705, hair follicles UBERON:0002073, and sweat glands UBERON:0001820. Oral mucosa and, rarely, ocular structures have been reported. Primary cardiovascular, pulmonary, hepatic, or marrow disease is not an established DPR feature. [52][246][81]
Tissue and cells Skin epidermis UBERON:0001003, particularly basal epidermal layer UBERON:0002025; basal keratinocytes CL:0000312 and suggested CL:0000646. Pigment-laden cells can be found in the underlying dermis; melanocytes CL:0000148 are relevant to pigment interpretation. [21][76][292]
Subcellular Principally the cytoplasmic keratin intermediate-filament network, GO:0045095/GO:0005882. A DPR-specific mitochondrial, ER, or lysosomal lesion is not established. [21][53][281]
Distribution and laterality Pigmentation often predominates on the trunk, with variable neck, face, flexural, limb, palm, sole, or oral involvement. Alopecia can be diffuse. DPR is not characteristically unilateral; distribution varies among individuals. [205][76][81]

8. Temporal development

Period or course feature Finding
Onset Usually neonatal or infancy/early childhood, insidious rather than an acute illness. Orphanet assigns infancy and neonatal onset. [52]
Early evolution Pigmentation can spread during early childhood. Nail and hair changes can emerge or become more apparent later; in one 2026 clinically diagnosed case, hair thinning and nail abnormalities began at puberty. That is a case observation, not a standard disease stage. [76][252]
Established course DPR pigmentation characteristically persists for life, unlike the classically fading pigmentation used to describe NFJS. Individual hair or nail findings can vary and progress. No validated early/intermediate/end-stage scheme or progression-rate estimate exists. [52][65]
Remission and critical periods Spontaneous disappearance of the characteristic DPR pigment pattern is not expected; no proven curative treatment-induced remission or defined therapeutic window has been reported. Dermatoglyphic differences reflect early development, but no prenatal intervention is established. [52][21]

9. Inheritance and population

Measure Best-supported entry
Prevalence Orphanet: <1 per 1,000,000; treat as a rarity estimate, not a measured DPR population survey. [52]
Incidence and carrier frequency Unknown; no reliable cases-per-100,000-per-year or population carrier-rate estimate. [52][65]
Published-case statistic A 2019 account reported 21 published DPR patients and, separately, 55 NFJS patients from nine families at that time. These are historical literature counts, not prevalence or penetrance denominators. PMID 30968399, DOI 10.1111/bjd.17997, article URL. [65][132]
Inheritance and expression Autosomal dominant with variable expressivity: relatives carrying a KRT14 variant can receive DPR, NFJS, or overlapping clinical labels. Numerical penetrance and age-dependent penetrance are not established. [21][65]
Anticipation, mosaicism, consanguinity No established repeat-expansion anticipation or quantified germline-mosaicism contribution. Consanguinity is not required by the dominant mechanism. Revertant mosaicism discussed for other KRT14 disorders should not be entered as proven DPR protection. [21][205]
Founder effect A shared haplotype suggested a possible common origin of Q7X in three NFJS families; this does not establish a DPR-wide founder allele. [21]
Geography, ancestry, sex, age distribution Reports span regions, without an established racial predilection, geographic prevalence gradient, or measured male:female ratio. The inheritance mechanism permits affected people of either sex. Presentation generally starts in infancy, even when diagnosis occurs in adulthood. [205][52][76]

10. Diagnostics

Practical diagnostic approach: recognize the childhood-onset, persistent pigment pattern and the hair–nail findings; inspect palms, soles, dermatoglyphics, sweating, teeth, and oral mucosa; document a pedigree; then seek heterozygous KRT14 sequence confirmation, particularly when NFJS, EBS, or a systemic reticulate-pigmentation disorder is plausible. A 2024 diagnostic review recommends using onset, distribution, and extracutaneous findings to reach a provisional classification while acknowledging overlap. PMID 39139099, DOI 10.1093/ced/llae322, published online 14 August 2024, article URL. [260][81][261]

Test or criterion Utility and limitation
Clinical examination and pedigree The pigmentation–nonscarring alopecia–nail-dystrophy combination is strongly suggestive; absent dermatoglyphics and abnormal sweating add support. A feature alone is not diagnostic. [52][21]
Dermoscopy and trichoscopy Can document reticulated pigmented and hypopigmented spots, perifollicular change, and palmar loss of ridge patterns. A 2023 single case demonstrated clinical use; no sensitivity or specificity is established. [76]
Skin biopsy May show basal-layer pigmentation/vacuolization, pigment incontinence and melanophages, with variable hyperkeratosis or mild inflammatory change. Findings support but do not uniquely establish DPR. [76][21]
Molecular testing Sequence KRT14 using a single-gene test or a panel that includes it for ectodermal dysplasia, palmoplantar keratoderma, or inherited skin fragility. Targeted exome sequencing identified c.19C>T in the molecularly confirmed 2024 family. Interpret the variant and its condition-specific ClinVar evidence alongside segregation and phenotype. [81][261][web:14626]
Broader WES/WGS Reasonable when presentation overlaps other inherited pigmentation disorders or the focused test is unrevealing; not demonstrated to outperform a well-targeted KRT14 assay for a classical presentation. [81][260]
Laboratory and differential-directed testing There is no established DPR blood, urine, enzyme, imaging, electrophysiology, or circulating biomarker test. CBC and telomere evaluation are relevant when dyskeratosis congenita is suspected, not routine DPR-confirmatory tests. In the 2024 case, normal telomere length helped challenge that alternative diagnosis. [81]
Tests without established routine role Chromosomal microarray/karyotype/FISH, mitochondrial sequencing, repeat-expansion assays, RNA-seq, proteomics, metabolomics, epigenomics, and liquid biopsy do not diagnose typical KRT14-associated DPR. Use them only for a separately justified differential. [81][21]
Differential diagnosis Distinguishing considerations
NFJS Same gene and substantial overlap; pigment is classically described as fading with age, and dental-enamel defects are more characteristic. Neither difference is absolute, as overlapping families demonstrate. [65][81]
Dyskeratosis congenita/telomere biology disorder Pigment and nail findings can mislead; evaluate characteristic nail pattern, oral leukoplakia, marrow/cancer history, and telomere findings as clinically indicated. Cancer or marrow failure must not automatically be attributed to DPR. [81]
Dowling–Degos disease, other inherited reticulate dyschromias, and EBS with mottled pigmentation Distribution, associated hair/nail/sweat findings, blistering history, histology, and appropriate gene testing help distinguish them. [76][260]

There is no DPR-specific universal newborn-screening program or formally validated standalone clinical scoring criterion in these sources. Once a familial variant is established, targeted testing of relatives is feasible with genetics input. [261][52]

11. Outcome and prognosis

DPR is generally described as a lifelong disorder of skin and appendages, rather than a progressive marrow-failure or malignancy syndrome. However, there are no reliable DPR-specific five- or ten-year survival rates, life-expectancy estimates, attributable mortality rates, disability scores, or validated prognostic biomarkers. Persistent pigmentation, hair and nail changes, troublesome keratoderma, impaired sweating, and occasional blisters account for recognized morbidity. Rare ocular observations should be assessed individually rather than assumed to predict outcome. [52][59][81]

The 2024 case demonstrates a consequential diagnostic distinction: the proband’s leukemia and his mother’s tongue cancer initially raised concern for dyskeratosis congenita, but the authors found KRT14-associated DPR and stated that the family cancer history remained unexplained; cancer had not previously been established as a DPR feature. Reclassification changed counseling about prognosis and screening burden and affected the family’s psychological well-being. One family cannot establish that all carriers lack unrelated cancer risk. PMID 39106435. [81]

12. Treatment and real-world implementation

There is no established disease-modifying cure or DPR-specific treatment algorithm. Treatment is individualized to symptoms; the observations below must not be turned into response-rate claims. [39][76]

Treatment or intervention Application and observed outcome Suggested annotation and evidence limit
Topical emollients and keratolytics Supportive care for thickened palms and soles; topical retinoic acids are also suggested for hyperkeratosis. This is symptom management, not pigment or genotype correction. [39][76] Use a locally verified NCIT supportive-care or dermatologic-intervention term; no exact NCIT keratolytic code is asserted here.
Etretinate, systemic retinoid A 1995 report describes successful treatment of DPR-associated palmoplantar keratoderma; the evidence is a case report, not a trial or an endorsement for routine use. PMID 7591467, DOI 10.1111/j.1365-4362.1995.tb01099.x, PubMed URL. Etretinate has substantial reproductive toxicity and was withdrawn from the US market. [344][322] ChEBI:4913; verify an appropriate NCIT retinoid term locally before coding a current intervention. [227]
Topical minoxidil 5% In one 2022 case, the patient reported substantially improved scalp hair density after six months. This is neither a controlled effect nor evidence that the underlying DPR changed. PMID 36225994, DOI 10.4103/idoj.idoj_698_21, article URL. [159][158] ChEBI:6942; suggested NCIT:C47623 (minoxidil). Monitor according to the formulation’s usual safety guidance; no DPR-specific adverse-event rate is available. [221][327]
Azelaic acid 20% Used on facial/neck pigmentation in that same case; reticulate pigmentation did not respond. Correct a coexisting deficiency separately: that patient’s additional B12-related flexural pigmentation improved with replenishment, which must not be counted as reversal of DPR. [159] Symptom-directed topical intervention; no DPR-specific response rate.
Heat precautions and hydration Practical support for those with impaired sweating or heat intolerance; tailor activity to the patient, since some patients sweat normally. [252][76] Supportive/behavioral intervention; not primary prevention.
Genetic counseling Explain dominant transmission, phenotype variability, testing of relatives, and reproductive options after identifying a familial variant. [47][65] NCIT:C15240 (Genetic Counseling). [323]

No DPR-specific gene, cell, RNA, targeted-molecular, or immunotherapy, disease-directed surgery, established pharmacogenomic rule, controlled combination regimen, response rate, or NCT-identified interventional trial was established by the disease-specific evidence reviewed here. Do not infer efficacy from EBS therapies merely because KRT14 is shared. [39][81][264]

13. Prevention

Level Defensible action
Primary There is no vaccine, antimicrobial prophylaxis, diet, or exposure avoidance that prevents a germline KRT14 variant. Offer genetic counseling and reproductive discussion when the familial variant is known; prenatal or preimplantation testing is technically possible in principle but requires individualized clinical genetics care. [21][323]
Secondary Recognize the phenotype early and confirm an informative familial variant where possible; offer targeted assessment of at-risk relatives. No population-wide or newborn DPR screening program is established. [52][261]
Tertiary Address hyperkeratosis and blisters, assess troublesome heat intolerance, and avoid attributing unrelated systemic signs to DPR without investigation. Preventing symptoms or diagnostic harm is not prevention of disease occurrence. [39][81][252]

14. Other species and naturally occurring disease

Species or group Taxonomy, ortholog, and natural-disease finding Comparative interpretation
Human Homo sapiens, NCBI Taxon 9606; causal gene KRT14, NCBI Gene 3861. [46] Reference DPR disease.
Domestic cat Felis catus, NCBI Taxon 9685; domestic shorthair breed VBO:0100119. A naturally affected cat had homozygous KRT14 c.979C>T, p.(Gln327*), causing EBS, not DPR. PMID 32657488, published online 13 July 2020, DOI 10.1111/age.12979, article URL. [266][268] Useful evidence of conserved epithelial need for K14, but its recessive blistering phenotype and later stop position must not be mislabeled as natural feline DPR. [266]
Other naturally affected species No naturally occurring nonhuman DPR phenotype was established by the reviewed evidence. The Mendelian condition is not infectious; zoonotic transmission does not apply. [264][266]

15. Model organisms and experimental systems

Model or resource What it demonstrates Limitation for DPR
Krt14 null mouse; Mus musculus, NCBI Taxon 10090; ortholog NCBI Gene 16664, MGI:96688 Homozygous targeted null mice develop severe skin blistering and generally die around two days after birth. K15 forms a residual, structurally different filament network. Mouse primary study: PMID 7539810, J Cell Biol 1995, DOI 10.1083/jcb.129.5.1329, article URL. [198][337] Primarily models severe K14 loss/EBS-like fragility, not the viable, heterozygous, early-head-truncation DPR phenotype. MGI lists no DPR-specific mouse model in its displayed human-disease model table. [264]
Krt14 null mouse with basal K16 expression Experimental K16 expression substantially rescued early blistering and neonatal lethality, though later alopecia, ulcers, and epithelial defects occurred. PMID 10477769, J Cell Biol 1999, DOI 10.1083/jcb.146.5.1185, article URL. [338][345] Demonstrates partial keratin functional compensation; not a tested DPR treatment or confirmed human protective modifier.
HaCaT keratinocytes with reduced KRT14 Greater TNF-α-induced apoptosis under the experimental conditions; doxycycline prevented that assay effect. In vitro, PMID 18049449. [web:18049449] Tests a pathway proposed for related NFJS, not whole-organism DPR pigmentation, dermatoglyphics, or natural history.
Human patient pedigrees and skin biopsies Establish sequence segregation, phenotype overlap, pigmentary pathology, and basal-cell ultrastructural findings. PMID 16960809; contemporary molecularly confirmed family PMID 39106435. [21][81] Small numbers and selective ascertainment prevent reliable penetrance, modifier, treatment-response, and prognosis estimates.

Knowledge-base priority: curate MONDO:0007445 → KRT14 (HGNC:6416) → early truncating germline variant → basal-keratinocyte filament dysfunction/apoptotic susceptibility → ectodermal and pigmentary findings, with the phenotype HPO terms above. Keep the pigment-pattern mechanism, DPR-specific penetrance, variant-specific severity, ClinVar conflict at c.54C>A, and lack of a DPR-faithful animal model explicitly marked unresolved rather than silently converting inference into fact. [47][21][web:18049449][web:14626][264]

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Outcome Count
References checked 20
Resolved 20
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 20
On topic 6
Off topic 2

References that may not be about this subject

These identifiers resolve, so they are not fabrications, but the records they resolve to share almost none of this report's vocabulary. That is a clue and not a verdict - a paper can be relevant in ways its title and abstract do not spell out - so read them before deciding:

  • PMC:PMC6440173 (1 mention) - Dermatopathia Pigmentosa Reticularis.
  • shared terms: nail
  • PMC:PMC5672609 (1 mention) - Clinical and Genetic Review of Hereditary Acral Reticulate Pigmentary Disorders.
  • shared terms: pigmentation, clinical

Weighed against this report's own most characteristic terms: dpr, krt14, established, variant, phenotype, skin, nfjs, dpr-specific, disease, url, sweating, affected, pigmentation, nail, gene, family, heterozygous, hair, clinical, human.

All extracted references resolved successfully. Resolving is not the same as being relevant, though - see the references listed above as possibly off topic.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 33
Resolved 29
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 4
Terms whose name was checked 6
Terms named correctly 0
Terms named as a different term 2
Terms whose name is worth a second look 4

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • HP:0008404 (1 mention) - the report calls it "Onychodystrophy—brittle, short, thickened or otherwise malformed nails; clinical sign"; HP calls it Nail dystrophy**
  • HP:0007455 (1 mention) - the report calls it "Adermatoglyphia, absent or poorly developed fingerprints; physical manifestation"; HP calls it Adermatoglyphia**

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • HP:0007588 (1 mention) - the report calls it "Generalized or truncal reticular hyperpigmentation; clinical sign"; HP calls it Reticular hyperpigmentation
  • HP:0000972 (1 mention) - the report calls it "Palmoplantar hyperkeratosis/keratoderma; clinical sign"; HP calls it Palmoplantar hyperkeratosis**
  • HP:0012788 (1 mention) - the report calls it "Reticulate oral-mucosal pigmentation; clinical sign"; HP calls it Reticulate pigmentation of oral mucosa**
  • HP:0000502 (1 mention) - the report calls it "Abnormal conjunctiva morphology or other ocular finding; clinical sign"; HP calls it Abnormal conjunctiva morphology**

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: OMIM, ORPHA, MGI.