Keratosis follicularis spinulosa decalvans

Mendelian MONDO:0000136 Pathograph 14 Genodermatosis Keratosis pilaris atrophicans

Keratosis follicularis spinulosa decalvans (KFSD) is a rare inherited genodermatosis of follicular keratinization. It usually begins in childhood with diffuse follicular hyperkeratosis and progressive cicatricial alopecia of the scalp, eyebrows, and eyelashes, with variable ocular involvement such as photophobia and corneal dystrophy. X-linked recessive KFSD is most often linked to MBTPS2 site-2 protease dysfunction, while rarer autosomal forms reflect additional follicular-keratinization mechanisms.

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4
Pathophys.
2
Histopath.
19
Phenotypes
14
Pathograph
4
Genes
3
Treatments
1
Differentials
1
References
1
Deep Research
⚙

Pathophysiology

4
MBTPS2 Site-2 Protease Dysfunction
MBTPS2 encodes site-2 protease, an intramembrane protease required for regulated cleavage of membrane-tethered transcription factors including SREBP and ATF6. KFSD-associated MBTPS2 missense variants reduce sterol responsiveness and plausibly perturb lipid homeostasis and unfolded-protein responses in follicular keratinocytes.
keratinocyte link
MBTPS2 link
sterol metabolic process link ↓ DECREASED endoplasmic reticulum unfolded protein response link ⚠ ABNORMAL
Downstream
Follicular Keratinization Defect Impaired MBTPS2-dependent membrane-protein processing disrupts follicular keratinocyte differentiation and follicular plugging.
Show evidence (2 references)
PMID:20672378 SUPPORT In Vitro
"MBTPS2 is required for cleavage of sterol regulatory element-binding proteins (SREBPs). In vitro functional expression studies of the c.1523A>G mutation showed that sterol responsiveness was reduced by half."
Functional expression studies show impaired sterol-responsive SREBP processing for a KFSD MBTPS2 variant.
PMID:33743732 SUPPORT Other
"The MBTPS2 is critical for a myriad of cellular processes, ranging from the regulation of cholesterol homeostasis to unfolded protein responses."
This review summarizes the key site-2 protease processes perturbed by MBTPS2 mutations.
CST6-Cathepsin Imbalance
In an autosomal dominant KFSD family, a CST6 variant altered cystatin M/E targeting and disrupted the balance between cystatin M/E and cathepsins L and V, with downstream changes in transglutaminase expression in patient keratinocytes.
keratinocyte link
CST6 link
proteolysis link ⚠ ABNORMAL keratinocyte differentiation link ⚠ ABNORMAL
Downstream
Follicular Keratinization Defect Dysregulated cystatin M/E-cathepsin balance disrupts keratinocyte differentiation in an autosomal dominant KFSD mechanism.
Show evidence (1 reference)
PMID:34322157 SUPPORT In Vitro
"The variant found in CST6 is expected to affect protein targeting and results in marked disruption of the balance between cystatin M/E activity and its target proteases and eventually transglutaminases 1 and 3."
The patient-cell study links the CST6 variant to dysregulated cystatin M/E target protease and cornification control.
Follicular Keratinization Defect
Abnormal follicular keratinization causes keratin occlusion, follicular plugging, and hyperkeratotic follicular papules involving scalp and vellus hair follicles.
hair follicle cell link keratinocyte link
keratinization link ⚠ ABNORMAL hair follicle development link ⚠ ABNORMAL
Downstream
Follicular Inflammation and Scarring Alopecia Keratin occlusion and follicular plugging promote inflammatory follicular injury.
Show evidence (2 references)
PMID:38087855 SUPPORT Human Clinical
"Vellus hair-associated follicular hyperkeratosis affected all of the patients."
The case series identifies follicular hyperkeratosis as universal in the studied KFSD patients.
PMID:28932071 SUPPORT Human Clinical
"Histopathology from a keratotic papule over the scalp showed follicular plugging, basket weave orthokeratosis, mild perivascular inflammatory infiltrate along with perifollicular fibrosis and a small vertical scar"
Histology from a KFSD patient shows follicular plugging and perifollicular fibrosis.
Follicular Inflammation and Scarring Alopecia
Follicular structural abnormalities trigger variable inflammation, loss of follicular openings, and irreversible cicatricial alopecia affecting the scalp, eyebrows, and eyelashes.
hair follicle cell link
inflammatory response link ↑ INCREASED
Downstream
Scarring alopecia of scalp Follicular destruction produces progressive cicatricial scalp alopecia.
Sparse eyebrow Terminal hair involvement includes eyebrows.
Sparse eyelashes Terminal hair involvement includes eyelashes.
Show evidence (1 reference)
PMID:38087855 SUPPORT Human Clinical
"We hypothesize that follicular changes in histopathology are the primary event that trigger variable inflammation and further follicular destruction."
The clinicopathologic series links primary follicular changes to inflammation and follicular destruction.
✶

Histopathology

2
Follicular plugging with perifollicular fibrosis
Biopsy can show follicular plugging, orthokeratosis, perifollicular inflammation, perifollicular fibrosis, and vertical scarring.
Show evidence (1 reference)
PMID:28932071 SUPPORT Human Clinical
"Follicular plugging, perifollicular fibrosis, and vertical scar"
The figure legend directly summarizes the diagnostic histopathologic findings.
Follicular isthmus keratin occlusion
Case-series histopathology shows structural hair-follicle abnormalities, including fused infundibula and follicular dilation at the isthmus level caused by keratin occlusion.
Show evidence (1 reference)
PMID:38087855 SUPPORT Human Clinical
"Follicular changes including fused infundibulum, the protrusion of the outer root sheath into the follicular canal, and a dilatation of the follicles at the isthmus level caused by the occlusion of keratin were observed."
The case series describes the follicular structural lesions that define the histopathology.
⬡

Pathograph

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

Phenotypes

19
Cardiovascular 2
Facial erythema FREQUENT Facial erythema (HP:0001041)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0001041 | Facial erythema | Frequent (79-30%)"
Orphanet lists facial erythema as frequent.
Conjunctivitis OCCASIONAL Conjunctivitis (HP:0000509)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0000509 | Conjunctivitis | Occasional (29-5%)"
Orphanet lists conjunctivitis as occasional.
Eye 4
Photophobia OCCASIONAL Photophobia (HP:0000613)
Show evidence (2 references)
ORPHA:2340 SUPPORT Other
"HP:0000613 | Photophobia | Occasional (29-5%)"
Orphanet lists photophobia as occasional.
PMID:38087855 SUPPORT Human Clinical
"photophobia was not a constant feature."
The case series supports variable, nonconstant photophobia.
Corneal dystrophy OCCASIONAL Corneal dystrophy (HP:0001131)
Show evidence (2 references)
ORPHA:2340 SUPPORT Other
"HP:0001131 | Corneal dystrophy | Occasional (29-5%)"
Orphanet lists corneal dystrophy as occasional.
PMID:20672378 SUPPORT Human Clinical
"Associated eye findings include photophobia in childhood and corneal dystrophy."
The MBTPS2 family paper describes corneal dystrophy among associated eye findings.
Blepharitis OCCASIONAL Blepharitis (HP:0000498)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0000498 | Blepharitis | Occasional (29-5%)"
Orphanet lists blepharitis as occasional.
Keratitis Keratitis (HP:0000491)
Show evidence (1 reference)
PMID:33743732 SUPPORT Human Clinical
"Extracutaneous features include photophobia, keratitis, blepharitis, and enamel hypoplasia."
The MBTPS2 review lists keratitis among extracutaneous KFSD features.
Head and Neck 2
Scarring alopecia of scalp FREQUENT Scarring alopecia of scalp (HP:0004552)
Show evidence (2 references)
ORPHA:2340 SUPPORT Other
"HP:0004552 | Scarring alopecia of scalp | Frequent (79-30%)"
Orphanet lists scarring alopecia of scalp as frequent.
PMID:38087855 SUPPORT Human Clinical
"Involvement of the scalp hairs leading to progressive scarring alopecia on the midline of the scalp with variable degrees of inflammation was the pathognomonic feature."
The case series identifies progressive scarring scalp alopecia as pathognomonic.
Enamel hypoplasia Enamel hypoplasia (HP:0006297)
Show evidence (1 reference)
PMID:33743732 SUPPORT Human Clinical
"Extracutaneous features include photophobia, keratitis, blepharitis, and enamel hypoplasia."
The MBTPS2 review lists enamel hypoplasia among extracutaneous KFSD features.
Immune 2
Folliculitis FREQUENT Folliculitis (HP:0025084)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0025084 | Folliculitis | Frequent (79-30%)"
Orphanet lists folliculitis as frequent.
Atopic dermatitis OCCASIONAL Atopic dermatitis (HP:0001047)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0001047 | Atopic dermatitis | Occasional (29-5%)"
Orphanet lists atopic dermatitis as occasional.
Integument 4
Keratosis pilaris FREQUENT Keratosis pilaris (HP:0032152)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0032152 | Keratosis pilaris | Frequent (79-30%)"
Orphanet lists keratosis pilaris as frequent.
Pruritus FREQUENT Pruritus (HP:0000989)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0000989 | Pruritus | Frequent (79-30%)"
Orphanet lists pruritus as frequent.
Palmoplantar keratoderma OCCASIONAL Palmoplantar keratoderma (HP:0000982)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0000982 | Palmoplantar keratoderma | Occasional (29-5%)"
Orphanet lists palmoplantar keratoderma as occasional.
Nail dystrophy OCCASIONAL Nail dystrophy (HP:0008404)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0008404 | Nail dystrophy | Occasional (29-5%)"
Orphanet lists nail dystrophy as occasional.
Other 5
Follicular hyperkeratosis FREQUENT Follicular hyperkeratosis (HP:0007502)
Show evidence (2 references)
ORPHA:2340 SUPPORT Other
"HP:0007502 | Follicular hyperkeratosis | Frequent (79-30%)"
Orphanet lists follicular hyperkeratosis as frequent.
PMID:38087855 SUPPORT Human Clinical
"Vellus hair-associated follicular hyperkeratosis affected all of the patients."
The case series directly observes follicular hyperkeratosis in all included patients.
Progressive alopecia FREQUENT Progressive alopecia (HP:0002287)
Show evidence (2 references)
ORPHA:2340 SUPPORT Other
"HP:0002287 | Progressive alopecia | Frequent (79-30%)"
Orphanet lists progressive alopecia as frequent.
PMID:20672378 SUPPORT Human Clinical
"characterized by development of hyperkeratotic follicular papules on the scalp followed by progressive alopecia of the scalp, eyelashes, and eyebrows."
The MBTPS2 family study describes progressive alopecia as a core clinical feature.
Sparse eyebrow FREQUENT Sparse eyebrow (HP:0045075)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0045075 | Sparse eyebrow | Frequent (79-30%)"
Orphanet lists sparse eyebrow as frequent.
Sparse eyelashes FREQUENT Sparse eyelashes (HP:0000653)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0000653 | Sparse eyelashes | Frequent (79-30%)"
Orphanet lists sparse eyelashes as frequent.
Hyperkeratotic papule FREQUENT Hyperkeratotic papule (HP:0045059)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"HP:0045059 | Hyperkeratotic papule | Frequent (79-30%)"
Orphanet lists hyperkeratotic papule as frequent.
🧬

Genetic Associations

4
MBTPS2 pathogenic variants (X-linked recessive causative pathogenic variants in MBTPS2.)
X-linked recessive
Show evidence (3 references)
ORPHA:2340 SUPPORT Other
"MBTPS2 | membrane bound transcription factor peptidase, site 2 | hgnc:15455 | Disease-causing germline mutation(s) in"
Orphanet records MBTPS2 as a disease-causing germline gene for KFSD.
PMID:20672378 SUPPORT Human Clinical
"Screening of all 14 genes in the candidate region identified MBTPS2 as the candidate gene carrying a c.1523A>G (p.Asn508Ser) missense mutation."
Linkage and candidate-region sequencing identified a segregating MBTPS2 missense variant in KFSD families.
PMID:27663151 SUPPORT Human Clinical
"Keratosis follicularis spinulosa decalvans (KFSD) is an X-linked condition characterized by keratotic follicular papules and progressive alopecia, which is caused by mutations in the MBTPS2 gene."
This mutation-update paper directly states the X-linked MBTPS2 cause.
CST6 autosomal dominant pathogenic variant (Rare autosomal dominant KFSD mechanism involving cystatin M/E dysfunction.)
Autosomal dominant
Show evidence (2 references)
PMID:34322157 SUPPORT Human Clinical
"Using whole-exome sequencing, we identified a heterozygous missense variant in CST6 in DNA samples from the index patient and her affected son."
Exome sequencing identified a CST6 variant segregating with autosomal dominant KFSD in a mother-son pair.
PMID:34322157 SUPPORT In Vitro
"Patient keratinocytes showed increased expression of cathepsin genes CTSL and CTSV and reduced expression of transglutaminase genes TGM1 and TGM3."
Patient keratinocyte assays support altered cystatin M/E target protease and cornification biology.
LRP1 keratosis pilaris atrophicans overlap (Orphanet-listed loss-of-function gene for the KFSD/KPA overlap spectrum.)
Autosomal recessive
Show evidence (2 references)
ORPHA:2340 SUPPORT Other
"LRP1 | LDL receptor related protein 1 | hgnc:6692 | Disease-causing germline mutation(s) (loss of function) in"
Orphanet records LRP1 as a disease-causing loss-of-function gene for this record.
PMID:26142438 PARTIAL Human Clinical
"CONCLUSIONS: This is the first report on LRP1 as a pathogenic gene for autosomal recessive KPA and keratosis pilaris."
This supports LRP1 in the overlapping keratosis pilaris atrophicans spectrum included under the Orphanet record.
SAT1 candidate gene (Candidate gene tested in Orphanet.)
Show evidence (1 reference)
ORPHA:2340 SUPPORT Other
"SAT1 | spermidine/spermine N1-acetyltransferase 1 | hgnc:10540 | Candidate gene tested in"
Orphanet lists SAT1 only as a candidate-tested gene, so it is modeled as an uncertain relationship.
💊

Treatments

3
Supportive topical keratolytics and emollients
Action: supportive care MAXO:0000950
Topical keratolytics and emollients are baseline supportive measures for follicular hyperkeratosis, although treatment response is often limited.
Target Phenotypes: Follicular hyperkeratosis ↗
Show evidence (1 reference)
PMID:28932071 SUPPORT Human Clinical
"Topical treatment comprises mainly of keratolytics and emollients."
The case report/review describes topical keratolytics and emollients as standard supportive topical care.
Oral retinoid pharmacotherapy
Action: Pharmacotherapy NCIT:C15986
Agent: isotretinoin ↗
Systemic retinoids such as isotretinoin can reduce follicular hyperkeratosis and inflammation in early disease, with case-level evidence of flattened papules and hair regrowth.
Target Phenotypes: Follicular hyperkeratosis ↗ Progressive alopecia ↗
Show evidence (2 references)
PMID:28932071 SUPPORT Human Clinical
"Following 1 month of therapy, there was marked flattening of the keratotic papules, and significant hair growth was seen by the 3rd month"
A KFSD patient treated with oral isotretinoin had improvement in papules and hair growth.
PMID:28932071 SUPPORT Human Clinical
"Systemic retinoids such as isotretinoin and etretinate are beneficial in the early stages of the disease as they downregulate follicular hyperkeratosis and inflammation."
The report summarizes retinoid utility for early inflammatory follicular hyperkeratosis.
Laser-assisted hair removal for recalcitrant disease
Action: Laser Therapy NCIT:C15466
Laser-assisted hair removal has been reported as an option for progressive or recalcitrant KFSD when follicular inflammation and papules persist.
Target Phenotypes: Follicular hyperkeratosis ↗
Show evidence (1 reference)
PMID:28932071 SUPPORT Human Clinical
"Laser assisted hair removal with the long-pulse non-Q-switched ruby laser has been found to be useful in progressive or recalcitrant KFSD."
The treatment review notes laser-assisted hair removal as an option for recalcitrant KFSD.
🔀

Differential Diagnoses

1

Conditions with similar clinical presentations that must be differentiated from Keratosis follicularis spinulosa decalvans:

IFAP syndrome Not Yet Curated MONDO:0100212
Overlapping Features IFAP syndrome overlaps through follicular ichthyosis/keratosis, alopecia, and photophobia, but KFSD is distinguished by progressive inflammatory scarring alopecia.
Show evidence (1 reference)
PMID:33743732 SUPPORT Human Clinical
"As the phenotypes of this disorder considerably simulates IFAP, KFSD is sometimes considered as a ‘milder form of IFAP, however, this disorder can be distinguished from IFAP via the nature of alopecia, which is progressive with variable degrees of inflammatory change leading to scarring in KFSD."
The MBTPS2 review states the clinical overlap and the scarring-alopecia discriminator.
{ }

Source YAML

click to show 
name: Keratosis follicularis spinulosa decalvans
creation_date: "2026-05-11T19:16:08Z"
updated_date: "2026-05-11T20:40:05Z"
description: >-
  Keratosis follicularis spinulosa decalvans (KFSD) is a rare inherited
  genodermatosis of follicular keratinization. It usually begins in childhood
  with diffuse follicular hyperkeratosis and progressive cicatricial alopecia
  of the scalp, eyebrows, and eyelashes, with variable ocular involvement such
  as photophobia and corneal dystrophy. X-linked recessive KFSD is most often
  linked to MBTPS2 site-2 protease dysfunction, while rarer autosomal forms
  reflect additional follicular-keratinization mechanisms.
category: Mendelian
disease_term:
  preferred_term: keratosis follicularis spinulosa decalvans
  term:
    id: MONDO:0000136
    label: keratosis follicularis spinulosa decalvans
parents:
- Genodermatosis
- Keratosis pilaris atrophicans
prevalence:
- population: Europe
  percentage: "<1 / 1,000,000"
  notes: Orphanet records KFSD as an ultra-rare disorder in Europe.
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "<1 / 1 000 000 | Europe | Point prevalence | ORPHANET"
    explanation: Orphanet provides the European point-prevalence class.
genetic:
- name: MBTPS2 pathogenic variants
  gene_term:
    preferred_term: MBTPS2
    term:
      id: hgnc:15455
      label: MBTPS2
  association: X-linked recessive causative pathogenic variants in MBTPS2.
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  inheritance:
  - name: X-linked recessive
    evidence:
    - reference: ORPHA:2340
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "- X-linked recessive"
      explanation: Orphanet lists X-linked recessive inheritance for KFSD.
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MBTPS2 | membrane bound transcription factor peptidase, site 2 | hgnc:15455 | Disease-causing germline mutation(s) in"
    explanation: Orphanet records MBTPS2 as a disease-causing germline gene for KFSD.
  - reference: PMID:20672378
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Screening of all 14 genes in the candidate region identified MBTPS2 as
      the candidate gene carrying a c.1523A>G (p.Asn508Ser) missense mutation.
    explanation: Linkage and candidate-region sequencing identified a segregating MBTPS2 missense variant in KFSD families.
  - reference: PMID:27663151
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Keratosis follicularis spinulosa decalvans (KFSD) is an X-linked
      condition characterized by keratotic follicular papules and progressive
      alopecia, which is caused by mutations in the MBTPS2 gene.
    explanation: This mutation-update paper directly states the X-linked MBTPS2 cause.
- name: CST6 autosomal dominant pathogenic variant
  gene_term:
    preferred_term: CST6
    term:
      id: hgnc:2478
      label: CST6
  association: Rare autosomal dominant KFSD mechanism involving cystatin M/E dysfunction.
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  inheritance:
  - name: Autosomal dominant
  evidence:
  - reference: PMID:34322157
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Using whole-exome sequencing, we identified a heterozygous missense
      variant in CST6 in DNA samples from the index patient and her affected
      son.
    explanation: Exome sequencing identified a CST6 variant segregating with autosomal dominant KFSD in a mother-son pair.
  - reference: PMID:34322157
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Patient keratinocytes showed increased expression of cathepsin genes CTSL
      and CTSV and reduced expression of transglutaminase genes TGM1 and TGM3.
    explanation: Patient keratinocyte assays support altered cystatin M/E target protease and cornification biology.
- name: LRP1 keratosis pilaris atrophicans overlap
  gene_term:
    preferred_term: LRP1
    term:
      id: hgnc:6692
      label: LRP1
  association: Orphanet-listed loss-of-function gene for the KFSD/KPA overlap spectrum.
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  inheritance:
  - name: Autosomal recessive
    evidence:
    - reference: ORPHA:2340
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "- Autosomal recessive"
      explanation: Orphanet lists autosomal recessive inheritance for KFSD.
  notes: >-
    The primary PMID evidence identifies LRP1 in autosomal recessive keratosis
    pilaris atrophicans, an overlapping Orphanet/MONDO parent spectrum rather
    than the classic X-linked MBTPS2 KFSD subtype.
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "LRP1 | LDL receptor related protein 1 | hgnc:6692 | Disease-causing germline mutation(s) (loss of function) in"
    explanation: Orphanet records LRP1 as a disease-causing loss-of-function gene for this record.
  - reference: PMID:26142438
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      CONCLUSIONS: This is the first report on LRP1 as a pathogenic gene for
      autosomal recessive KPA and keratosis pilaris.
    explanation: This supports LRP1 in the overlapping keratosis pilaris atrophicans spectrum included under the Orphanet record.
- name: SAT1 candidate gene
  gene_term:
    preferred_term: SAT1
    term:
      id: hgnc:10540
      label: SAT1
  association: Candidate gene tested in Orphanet.
  relationship_type: UNKNOWN
  variant_origin: GERMLINE
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SAT1 | spermidine/spermine N1-acetyltransferase 1 | hgnc:10540 | Candidate gene tested in"
    explanation: Orphanet lists SAT1 only as a candidate-tested gene, so it is modeled as an uncertain relationship.
pathophysiology:
- name: MBTPS2 Site-2 Protease Dysfunction
  description: >-
    MBTPS2 encodes site-2 protease, an intramembrane protease required for
    regulated cleavage of membrane-tethered transcription factors including
    SREBP and ATF6. KFSD-associated MBTPS2 missense variants reduce sterol
    responsiveness and plausibly perturb lipid homeostasis and unfolded-protein
    responses in follicular keratinocytes.
  genes:
  - preferred_term: MBTPS2
    term:
      id: hgnc:15455
      label: MBTPS2
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: sterol metabolic process
    term:
      id: GO:0016125
      label: sterol metabolic process
    modifier: DECREASED
  - preferred_term: endoplasmic reticulum unfolded protein response
    term:
      id: GO:0030968
      label: endoplasmic reticulum unfolded protein response
    modifier: ABNORMAL
  evidence:
  - reference: PMID:20672378
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      MBTPS2 is required for cleavage of sterol regulatory element-binding
      proteins (SREBPs). In vitro functional expression studies of the
      c.1523A>G mutation showed that sterol responsiveness was reduced by half.
    explanation: Functional expression studies show impaired sterol-responsive SREBP processing for a KFSD MBTPS2 variant.
  - reference: PMID:33743732
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The MBTPS2 is critical for a myriad of cellular processes, ranging from
      the regulation of cholesterol homeostasis to unfolded protein responses.
    explanation: This review summarizes the key site-2 protease processes perturbed by MBTPS2 mutations.
  downstream:
  - target: Follicular Keratinization Defect
    description: Impaired MBTPS2-dependent membrane-protein processing disrupts follicular keratinocyte differentiation and follicular plugging.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - reduced SREBP cleavage and sterol responsiveness
    - abnormal unfolded-protein response signaling
- name: CST6-Cathepsin Imbalance
  description: >-
    In an autosomal dominant KFSD family, a CST6 variant altered cystatin M/E
    targeting and disrupted the balance between cystatin M/E and cathepsins L
    and V, with downstream changes in transglutaminase expression in patient
    keratinocytes.
  genes:
  - preferred_term: CST6
    term:
      id: hgnc:2478
      label: CST6
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: proteolysis
    term:
      id: GO:0006508
      label: proteolysis
    modifier: ABNORMAL
  - preferred_term: keratinocyte differentiation
    term:
      id: GO:0030216
      label: keratinocyte differentiation
    modifier: ABNORMAL
  evidence:
  - reference: PMID:34322157
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The variant found in CST6 is expected to affect protein targeting and
      results in marked disruption of the balance between cystatin M/E activity
      and its target proteases and eventually transglutaminases 1 and 3.
    explanation: The patient-cell study links the CST6 variant to dysregulated cystatin M/E target protease and cornification control.
  downstream:
  - target: Follicular Keratinization Defect
    description: Dysregulated cystatin M/E-cathepsin balance disrupts keratinocyte differentiation in an autosomal dominant KFSD mechanism.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Follicular Keratinization Defect
  description: >-
    Abnormal follicular keratinization causes keratin occlusion, follicular
    plugging, and hyperkeratotic follicular papules involving scalp and vellus
    hair follicles.
  cell_types:
  - preferred_term: hair follicle cell
    term:
      id: CL:0002559
      label: hair follicle cell
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: keratinization
    term:
      id: GO:0031424
      label: keratinization
    modifier: ABNORMAL
  - preferred_term: hair follicle development
    term:
      id: GO:0001942
      label: hair follicle development
    modifier: ABNORMAL
  evidence:
  - reference: PMID:38087855
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vellus hair-associated follicular hyperkeratosis affected all of the
      patients.
    explanation: The case series identifies follicular hyperkeratosis as universal in the studied KFSD patients.
  - reference: PMID:28932071
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Histopathology from a keratotic papule over the scalp showed follicular
      plugging, basket weave orthokeratosis, mild perivascular inflammatory
      infiltrate along with perifollicular fibrosis and a small vertical scar
    explanation: Histology from a KFSD patient shows follicular plugging and perifollicular fibrosis.
  downstream:
  - target: Follicular Inflammation and Scarring Alopecia
    description: Keratin occlusion and follicular plugging promote inflammatory follicular injury.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - keratin occlusion at the follicular isthmus
    - perifollicular inflammatory response
- name: Follicular Inflammation and Scarring Alopecia
  description: >-
    Follicular structural abnormalities trigger variable inflammation, loss of
    follicular openings, and irreversible cicatricial alopecia affecting the
    scalp, eyebrows, and eyelashes.
  cell_types:
  - preferred_term: hair follicle cell
    term:
      id: CL:0002559
      label: hair follicle cell
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  evidence:
  - reference: PMID:38087855
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We hypothesize that follicular changes in histopathology are the primary
      event that trigger variable inflammation and further follicular
      destruction.
    explanation: The clinicopathologic series links primary follicular changes to inflammation and follicular destruction.
  downstream:
  - target: Scarring alopecia of scalp
    description: Follicular destruction produces progressive cicatricial scalp alopecia.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Sparse eyebrow
    description: Terminal hair involvement includes eyebrows.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Sparse eyelashes
    description: Terminal hair involvement includes eyelashes.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
phenotypes:
- category: Dermatologic
  name: Follicular hyperkeratosis
  frequency: FREQUENT
  description: Follicular hyperkeratosis is a frequent core cutaneous feature.
  phenotype_term:
    preferred_term: Follicular hyperkeratosis
    term:
      id: HP:0007502
      label: Follicular hyperkeratosis
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0007502 | Follicular hyperkeratosis | Frequent (79-30%)"
    explanation: Orphanet lists follicular hyperkeratosis as frequent.
  - reference: PMID:38087855
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vellus hair-associated follicular hyperkeratosis affected all of the
      patients.
    explanation: The case series directly observes follicular hyperkeratosis in all included patients.
- category: Dermatologic
  name: Scarring alopecia of scalp
  frequency: FREQUENT
  description: Progressive cicatricial alopecia of the scalp is a defining feature.
  phenotype_term:
    preferred_term: Scarring alopecia of scalp
    term:
      id: HP:0004552
      label: Scarring alopecia of scalp
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0004552 | Scarring alopecia of scalp | Frequent (79-30%)"
    explanation: Orphanet lists scarring alopecia of scalp as frequent.
  - reference: PMID:38087855
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Involvement of the scalp hairs leading to progressive scarring alopecia
      on the midline of the scalp with variable degrees of inflammation was the
      pathognomonic feature.
    explanation: The case series identifies progressive scarring scalp alopecia as pathognomonic.
- category: Dermatologic
  name: Progressive alopecia
  frequency: FREQUENT
  description: Alopecia progresses over time and can involve scalp, eyebrows, and eyelashes.
  phenotype_term:
    preferred_term: Progressive alopecia
    term:
      id: HP:0002287
      label: Progressive alopecia
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002287 | Progressive alopecia | Frequent (79-30%)"
    explanation: Orphanet lists progressive alopecia as frequent.
  - reference: PMID:20672378
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      characterized by development of hyperkeratotic follicular papules on the
      scalp followed by progressive alopecia of the scalp, eyelashes, and
      eyebrows.
    explanation: The MBTPS2 family study describes progressive alopecia as a core clinical feature.
- category: Dermatologic
  name: Sparse eyebrow
  frequency: FREQUENT
  description: Eyebrow loss or sparseness is frequent.
  phenotype_term:
    preferred_term: Sparse eyebrow
    term:
      id: HP:0045075
      label: Sparse eyebrow
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0045075 | Sparse eyebrow | Frequent (79-30%)"
    explanation: Orphanet lists sparse eyebrow as frequent.
- category: Dermatologic
  name: Sparse eyelashes
  frequency: FREQUENT
  description: Eyelash loss or sparseness is frequent.
  phenotype_term:
    preferred_term: Sparse eyelashes
    term:
      id: HP:0000653
      label: Sparse eyelashes
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000653 | Sparse eyelashes | Frequent (79-30%)"
    explanation: Orphanet lists sparse eyelashes as frequent.
- category: Dermatologic
  name: Hyperkeratotic papule
  frequency: FREQUENT
  description: Hyperkeratotic papules occur as follicular keratin plugs.
  phenotype_term:
    preferred_term: Hyperkeratotic papule
    term:
      id: HP:0045059
      label: Hyperkeratotic papule
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0045059 | Hyperkeratotic papule | Frequent (79-30%)"
    explanation: Orphanet lists hyperkeratotic papule as frequent.
- category: Dermatologic
  name: Keratosis pilaris
  frequency: FREQUENT
  description: Keratosis pilaris is part of the follicular keratosis spectrum.
  phenotype_term:
    preferred_term: Keratosis pilaris
    term:
      id: HP:0032152
      label: Keratosis pilaris
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0032152 | Keratosis pilaris | Frequent (79-30%)"
    explanation: Orphanet lists keratosis pilaris as frequent.
- category: Dermatologic
  name: Folliculitis
  frequency: FREQUENT
  description: Follicular inflammation is frequent in the affected skin.
  phenotype_term:
    preferred_term: Folliculitis
    term:
      id: HP:0025084
      label: Folliculitis
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0025084 | Folliculitis | Frequent (79-30%)"
    explanation: Orphanet lists folliculitis as frequent.
- category: Dermatologic
  name: Facial erythema
  frequency: FREQUENT
  description: Facial erythema is frequent.
  phenotype_term:
    preferred_term: Facial erythema
    term:
      id: HP:0001041
      label: Facial erythema
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001041 | Facial erythema | Frequent (79-30%)"
    explanation: Orphanet lists facial erythema as frequent.
- category: Dermatologic
  name: Pruritus
  frequency: FREQUENT
  description: Pruritus is frequent.
  phenotype_term:
    preferred_term: Pruritus
    term:
      id: HP:0000989
      label: Pruritus
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000989 | Pruritus | Frequent (79-30%)"
    explanation: Orphanet lists pruritus as frequent.
- category: Dermatologic
  name: Palmoplantar keratoderma
  frequency: OCCASIONAL
  description: Palmoplantar keratoderma can occur in some patients.
  phenotype_term:
    preferred_term: Palmoplantar keratoderma
    term:
      id: HP:0000982
      label: Palmoplantar keratoderma
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000982 | Palmoplantar keratoderma | Occasional (29-5%)"
    explanation: Orphanet lists palmoplantar keratoderma as occasional.
- category: Dermatologic
  name: Atopic dermatitis
  frequency: OCCASIONAL
  description: Atopic dermatitis is reported occasionally.
  phenotype_term:
    preferred_term: Atopic dermatitis
    term:
      id: HP:0001047
      label: Atopic dermatitis
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001047 | Atopic dermatitis | Occasional (29-5%)"
    explanation: Orphanet lists atopic dermatitis as occasional.
- category: Dermatologic
  name: Nail dystrophy
  frequency: OCCASIONAL
  description: Nail dystrophy is an occasional ectodermal feature.
  phenotype_term:
    preferred_term: Nail dystrophy
    term:
      id: HP:0008404
      label: Nail dystrophy
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0008404 | Nail dystrophy | Occasional (29-5%)"
    explanation: Orphanet lists nail dystrophy as occasional.
- category: Ophthalmologic
  name: Photophobia
  frequency: OCCASIONAL
  description: Photophobia is variable and not present in every patient.
  phenotype_term:
    preferred_term: Photophobia
    term:
      id: HP:0000613
      label: Photophobia
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000613 | Photophobia | Occasional (29-5%)"
    explanation: Orphanet lists photophobia as occasional.
  - reference: PMID:38087855
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "photophobia was not a constant feature."
    explanation: The case series supports variable, nonconstant photophobia.
- category: Ophthalmologic
  name: Corneal dystrophy
  frequency: OCCASIONAL
  description: Corneal dystrophy can accompany the follicular phenotype.
  phenotype_term:
    preferred_term: Corneal dystrophy
    term:
      id: HP:0001131
      label: Corneal dystrophy
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001131 | Corneal dystrophy | Occasional (29-5%)"
    explanation: Orphanet lists corneal dystrophy as occasional.
  - reference: PMID:20672378
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Associated eye findings include photophobia in childhood and corneal dystrophy."
    explanation: The MBTPS2 family paper describes corneal dystrophy among associated eye findings.
- category: Ophthalmologic
  name: Blepharitis
  frequency: OCCASIONAL
  description: Blepharitis is an occasional ocular-adnexal manifestation.
  phenotype_term:
    preferred_term: Blepharitis
    term:
      id: HP:0000498
      label: Blepharitis
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000498 | Blepharitis | Occasional (29-5%)"
    explanation: Orphanet lists blepharitis as occasional.
- category: Ophthalmologic
  name: Keratitis
  description: Keratitis is reported among extracutaneous ocular manifestations.
  phenotype_term:
    preferred_term: Keratitis
    term:
      id: HP:0000491
      label: Keratitis
  evidence:
  - reference: PMID:33743732
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Extracutaneous features include photophobia, keratitis, blepharitis, and enamel hypoplasia."
    explanation: The MBTPS2 review lists keratitis among extracutaneous KFSD features.
- category: Ophthalmologic
  name: Conjunctivitis
  frequency: OCCASIONAL
  description: Conjunctivitis is occasional.
  phenotype_term:
    preferred_term: Conjunctivitis
    term:
      id: HP:0000509
      label: Conjunctivitis
  evidence:
  - reference: ORPHA:2340
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000509 | Conjunctivitis | Occasional (29-5%)"
    explanation: Orphanet lists conjunctivitis as occasional.
- category: Dental
  name: Enamel hypoplasia
  description: Enamel hypoplasia is reported as an extracutaneous feature.
  phenotype_term:
    preferred_term: Enamel hypoplasia
    term:
      id: HP:0006297
      label: Enamel hypoplasia
  evidence:
  - reference: PMID:33743732
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Extracutaneous features include photophobia, keratitis, blepharitis, and enamel hypoplasia."
    explanation: The MBTPS2 review lists enamel hypoplasia among extracutaneous KFSD features.
diagnosis:
- name: Clinical and trichoscopic recognition
  description: >-
    Diagnosis is based on terminal-hair involvement with follicular
    hyperkeratosis of vellus follicles; trichoscopy can show perifollicular
    scaling, tufted hairs, and loss of follicular openings.
  evidence:
  - reference: PMID:38087855
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In conclusion, terminal hair involvement, either scalp hairs, eyebrows,
      or eyelashes, and the hyperkeratosis of the follicle of vellus hairs is
      the diagnostic basis of KFSD.
    explanation: The clinicopathologic series states the diagnostic basis.
  - reference: PMID:38087855
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The trichoscopic features included perifollicular scaling, tufted hairs,
      and loss of follicular openings.
    explanation: This supports trichoscopy as an adjunctive clinical diagnostic approach.
- name: MBTPS2 molecular genetic testing
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: MAXO:0000533
      label: molecular genetic testing
  description: >-
    Molecular testing of MBTPS2 confirms X-linked KFSD and helps distinguish it
    from overlapping follicular keratosis, ichthyosis-follicularis, and Olmsted
    syndrome presentations.
  evidence:
  - reference: PMID:27663151
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Sanger sequencing was performed to detect mutations in the entire coding
      region of MBTPS2. A novel missense mutation (c.599C>T) was identified in
      the patient, confirming a diagnosis of KFSD.
    explanation: The report supports MBTPS2 sequencing as confirmatory diagnostic testing.
- name: Scalp skin biopsy
  diagnosis_term:
    preferred_term: biopsy of skin
    term:
      id: MAXO:0000423
      label: biopsy of skin
  description: >-
    Histopathology supports diagnosis by showing follicular plugging,
    orthokeratosis, perifollicular inflammation/fibrosis, and scarring.
  evidence:
  - reference: PMID:28932071
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Histopathology from a keratotic papule over the scalp showed follicular
      plugging, basket weave orthokeratosis, mild perivascular inflammatory
      infiltrate along with perifollicular fibrosis and a small vertical scar
    explanation: A biopsy from a KFSD patient showed characteristic follicular plugging and scarring.
histopathology:
- name: Follicular plugging with perifollicular fibrosis
  description: >-
    Biopsy can show follicular plugging, orthokeratosis, perifollicular
    inflammation, perifollicular fibrosis, and vertical scarring.
  evidence:
  - reference: PMID:28932071
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Follicular plugging, perifollicular fibrosis, and vertical scar"
    explanation: The figure legend directly summarizes the diagnostic histopathologic findings.
- name: Follicular isthmus keratin occlusion
  description: >-
    Case-series histopathology shows structural hair-follicle abnormalities,
    including fused infundibula and follicular dilation at the isthmus level
    caused by keratin occlusion.
  evidence:
  - reference: PMID:38087855
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Follicular changes including fused infundibulum, the protrusion of the
      outer root sheath into the follicular canal, and a dilatation of the
      follicles at the isthmus level caused by the occlusion of keratin were
      observed.
    explanation: The case series describes the follicular structural lesions that define the histopathology.
treatments:
- name: Supportive topical keratolytics and emollients
  description: >-
    Topical keratolytics and emollients are baseline supportive measures for
    follicular hyperkeratosis, although treatment response is often limited.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  target_phenotypes:
  - preferred_term: Follicular hyperkeratosis
    term:
      id: HP:0007502
      label: Follicular hyperkeratosis
  evidence:
  - reference: PMID:28932071
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Topical treatment comprises mainly of keratolytics and emollients."
    explanation: The case report/review describes topical keratolytics and emollients as standard supportive topical care.
- name: Oral retinoid pharmacotherapy
  description: >-
    Systemic retinoids such as isotretinoin can reduce follicular
    hyperkeratosis and inflammation in early disease, with case-level evidence
    of flattened papules and hair regrowth.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: isotretinoin
      term:
        id: CHEBI:6067
        label: isotretinoin
  target_phenotypes:
  - preferred_term: Follicular hyperkeratosis
    term:
      id: HP:0007502
      label: Follicular hyperkeratosis
  - preferred_term: Progressive alopecia
    term:
      id: HP:0002287
      label: Progressive alopecia
  evidence:
  - reference: PMID:28932071
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Following 1 month of therapy, there was marked flattening of the
      keratotic papules, and significant hair growth was seen by the 3rd month
    explanation: A KFSD patient treated with oral isotretinoin had improvement in papules and hair growth.
  - reference: PMID:28932071
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Systemic retinoids such as isotretinoin and etretinate are beneficial in
      the early stages of the disease as they downregulate follicular
      hyperkeratosis and inflammation.
    explanation: The report summarizes retinoid utility for early inflammatory follicular hyperkeratosis.
- name: Laser-assisted hair removal for recalcitrant disease
  description: >-
    Laser-assisted hair removal has been reported as an option for progressive
    or recalcitrant KFSD when follicular inflammation and papules persist.
  treatment_term:
    preferred_term: Laser Therapy
    term:
      id: NCIT:C15466
      label: Laser Therapy
  target_phenotypes:
  - preferred_term: Follicular hyperkeratosis
    term:
      id: HP:0007502
      label: Follicular hyperkeratosis
  evidence:
  - reference: PMID:28932071
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Laser assisted hair removal with the long-pulse non-Q-switched ruby laser
      has been found to be useful in progressive or recalcitrant KFSD.
    explanation: The treatment review notes laser-assisted hair removal as an option for recalcitrant KFSD.
differential_diagnoses:
- name: IFAP syndrome
  disease_term:
    preferred_term: IFAP syndrome
    term:
      id: MONDO:0100212
      label: IFAP syndrome
  description: >-
    IFAP syndrome overlaps through follicular ichthyosis/keratosis, alopecia,
    and photophobia, but KFSD is distinguished by progressive inflammatory
    scarring alopecia.
  evidence:
  - reference: PMID:33743732
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      As the phenotypes of this disorder considerably simulates IFAP, KFSD is
      sometimes considered as a ‘milder form of IFAP, however, this disorder can
      be distinguished from IFAP via the nature of alopecia, which is
      progressive with variable degrees of inflammatory change leading to
      scarring in KFSD.
    explanation: The MBTPS2 review states the clinical overlap and the scarring-alopecia discriminator.
references:
- reference: ORPHA:2340
  title: Keratosis follicularis spinulosa decalvans
  findings:
  - statement: ORPHA:2340 provides the disease definition, inheritance modes, prevalence, gene rows, HPO phenotype frequencies, and exact MONDO mapping.
    supporting_text: "MONDO:0000136 | Exact"
  - statement: ORPHA:2340 imports all listed phenotype-frequency rows into this first-pass curation.
    supporting_text: "HP:0007502 | Follicular hyperkeratosis | Frequent (79-30%)"
📚

References & Deep Research

References

1
ORPHA:2340
Keratosis follicularis spinulosa decalvans
2 findings
ORPHA:2340 provides the disease definition, inheritance modes, prevalence, gene rows, HPO phenotype frequencies, and exact MONDO mapping.
"MONDO:0000136 | Exact"
ORPHA:2340 imports all listed phenotype-frequency rows into this first-pass curation.
"HP:0007502 | Follicular hyperkeratosis | Frequent (79-30%)"

Deep Research

1
Asta ▸
Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Keratosis follicularis spinulosa decalvans. Core disease mechanisms, molec...
Asta Scientific Corpus Retrieval 14 citations 2026-05-11T12:41:56.190721

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Keratosis follicularis spinulosa decalvans. Core disease mechanisms, molec...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 14
  • Snippets retrieved: 20

Relevant Papers

[1] Keratosis Follicularis Spinulosa Decalvans in a female child- a rare presentation

  • Authors: Joyeeta Chowdhury, Loknath Ghoshal, S. Bannerjee
  • Year: 2017
  • Venue: Bangladesh Journal of Medical Science
  • URL: https://www.semanticscholar.org/paper/5e9f0cad42322d13b2cf3e594acb6befe3b8f955
  • DOI: 10.3329/BJMS.V16I4.33617
  • Citations: 1
  • Summary: A 6 year old girl came to us with total alopecia and multiple horny keratosis pilaris like skin lesions all over the body and was diagnosed as Keratosis follicularis spinulosa decalvans.
  • Evidence snippets:
  • Snippet 1 (score: 0.645) > Keratosis Follicularis Spinulosa Decalvans in a female child- a rare presentation

[2] Keratosis Follicularis Spinulosa Decalvans: A Rare Cause of Scarring Alopecia in Two Young Indian Girls

  • Authors: Uma G Maheswari, V. Chaitra, S. S. Mohan
  • Year: 2013
  • Venue: International Journal of Trichology
  • URL: https://www.semanticscholar.org/paper/e5d84025fd4a49921f9ebe7c6684eeb931f4cb8d
  • DOI: 10.4103/0974-7753.114713
  • PMID: 23960394
  • PMCID: 3746224
  • Citations: 10
  • Summary: Two sisters with severe form of KFSD are presented, progressing to scarring alopecia and follicular hyperkeratosis.
  • Evidence snippets:
  • Snippet 1 (score: 0.626) > Keratosis Follicularis Spinulosa Decalvans: A Rare Cause of Scarring Alopecia in Two Young Indian Girls

[3] Keratosis follicularis spinulosa decalvans: case report.

  • Authors: A. Berbert, S. A. Mantese, A. Rocha, Cláudia P Cherin, C. M. Couto
  • Year: 2010
  • Venue: Anais brasileiros de dermatologia
  • URL: https://www.semanticscholar.org/paper/92bc743c0fe409b45a2371207b99069be87e48b0
  • DOI: 10.1590/S0365-05962010000400017
  • PMID: 20944916
  • Citations: 9
  • Influential citations: 1
  • Summary: It is reported a case of child with intense cicatricial alopecia, with precocious changes that rapidly evolved to diffuse cic atricials on the scalp, which has limited the treatment, with disappointing results.
  • Evidence snippets:
  • Snippet 1 (score: 0.596) > Atrophic pillar keratosis comprehends three conditions that differ from each other according to the location of the lesions and level of inflammation and atrophy .They are : pillar keratosis face atrophying, atrophodermia vermiculata and keratosis follicularis spinulosa decalvans, possibly belonging to the same pathologic process, characterized by follicular hyperkeratosis with inflammation and subsequent atrophy. 1,4 ecently other authors have included a fourth type named folliculitis spinulosa decalvans, previously considered a persistent inflammatory variation of keratosis follicularis spinulosa decalvans 6 The term keratosis follicularis spinulosa decalvans was criated by Siemens, 7 in 1926, when he described some individuals from a Bavarian family that presented follicular papules on the face, trunk and extremities with partial loss of hairs on these areas and from that moment the disease became known as Siemens syndrome. Genetic studies in Dutch and English families showed connection with the Xp21.2-p22 gene. 8 However, other family analyses without evidence of inheritance linked to X suggest heterogeneous transmissions 1,3,4,9 and also sporadic 6 ones. > This disease starts in the early years of life, initially on the face and progressing towards the trunk and limbs and it might spread to other parts of the body. Palm-plantar hyperkeratosis, photophobia, corneal abnormalities and atopies can be associated. 1 Men are more seriously affected by the disease 1 . > The pathophysiology of the destruction of the pilar follicle is not well known yet. The first changes observed are hyperkeratosis and hypergranulosis of the infundibulum and isthmus, which cause inflammatory reaction (at the begining acute and lately chronic, with mononuclear infiltrate) on the epidermis and on the papillary dermis. Chronic changes are followed by fibrosis and the destruction of the follicle. > However, hyperkertosis does not seem to be the primary event; keratinocyte disorders would precipitate abnormal liberation of cytokine resulting in hyperkeratosis and inflammatory reactions. 3
  • Snippet 2 (score: 0.563) > Keratosis follicularis spinulosa decalvans is a rare disease, with genetic transmission either X-linked or sporadic, characterized by follicular hyperkeratosis and cicatricial alopecia. The disease usually begins in early childhood exacerbating throughout adolescence. The therapies are somewhat effective, with frustrating treatment when there are changes which are predominantly cicatricial. It is reported a case of child with intense cicatricial alopecia, with precocious changes (already present at birth) that rapidly evolved to diffuse cicatricial alopecia on the scalp, which has limited the treatment, with disappointing results.
  • Snippet 3 (score: 0.542) > Keratosis follicularis spinulosa decalvans is a rare disease characterized by follicular hyperkeratosis and cicatricial alopecia. There are many sporadic cases but the most intensive manifestations are found in men suggesting a pattern of inheritance linked to X. 1,2,3,4 Manisfestations of the disease start in childhood, frequently on the face, but it might be circumscribed to the face and extremities or generalized. Cicatricial alopecia on the scalp and supercilium is the marking characterisitc of the disease. Some cases show association with corneal opacity, photophobia and palm-plantar hyperkeratosis that usually start in adolescence 1,2 Up to this moment a completely effec-tive therapy is not known.
  • Snippet 4 (score: 0.537) > However, hyperkertosis does not seem to be the primary event; keratinocyte disorders would precipitate abnormal liberation of cytokine resulting in hyperkeratosis and inflammatory reactions. 3 he most important differential diagnoses for keratosis follicularis spinulosa decalvans are: KID syndrome (keratosis, ichthyosis, deafness), atrichia with papular lesions, and inherited mucoepithelial dystrophia. 5,10 is specific case refers to a female child, born from consaguineous parents presenting severe cicatricial alopecia that in general occurs in sporadic cases. The child was examined by specialists in genetics but it was not possible to determine if it was due to genetic inheritance or if it was a case of sporadic manifestation. > Keratosis follicularis spinulosa decalvans can present phases of more intense inflammatory activity in childhood, getting better throughout adolescence, which does not impede the slow progression to cicatricial alopecia in a later phase. > The present case calls the attention for its gravity and precocity of changes (at birth) with difuse cicatricial alopecia on the scalp of a female patient. > The treatment is frustating, with a few reports of slight improvement in cases at an early stage that present a major inflammatory component. The improvement, in general, refers only to stabilization of the alopecia and clinical improvement of the areas that present erythema and pustulas. Keratolytics, topical and intra lesions corticoids can reduce hyperkertosis and inflammation, to a certain extent only. > Different systemic treatments including isotretinoin, etretinate, dapsone and antibiotics have been tried with varied results 5,6,11 It is suggested that the use of retinoids in the early and more active phase of the disease, when histopathology shows perifollicular infiltrate, can bring some benefit. 3 reatment is even more disappointing when the disease predominantly shows cicatricial changes, as in this present study. Treatment in this circumstance is reduced only to the use of topical paliative medication.

[4] Keratosis follicularis spinulosa decalvans in a 15 months Cypriot girl

  • Authors: A. Kaptanoğlu, C. Dalkan, F. Baba
  • Year: 2016
  • Venue: Indian Journal of Paediatric Dermatology
  • URL: https://www.semanticscholar.org/paper/c6462a8257fc77f41a2eca4f9e29b2e2817a339e
  • DOI: 10.4103/2319-7250.179502
  • Summary: A Cypriot girl that diagnosed KFSD that do not have any family history is reported, which is a rare disease with unknown etiology that occurs after puberty by the development of scalp pustules with bacterial infection.
  • Evidence snippets:
  • Snippet 1 (score: 0.595) > Keratosis follicularis spinulosa decalvans in a 15 months Cypriot girl
  • Snippet 2 (score: 0.563) > Keratosis follicularis spinulosa decalvans (KFSD) is a rare disease with unknown etiology. It clinically presents with diffuse follicular hyperkeratosis of scalp which progress to atrophy, cicatricial alopecia, and photophobia. The lesions start in chilhood and an aggrevasion occurs after puberty by the development of scalp pustules with bacterial infection and causes both functional and cosmetic discomfort. Here, we report a Cypriot girl that diagnosed KFSD that do not have any family history.

[5] Keratosis follicularis spinulosa decalvans: A dermoscopic perspective

  • Authors: S. Chintagunta, Priyanka S. Jaju
  • Year: 2020
  • Venue: Indian Journal of Paediatric Dermatology
  • URL: https://www.semanticscholar.org/paper/cf074ded3a25e7b3923d9c7b924293032156eba3
  • DOI: 10.4103/ijpd.IJPD_133_19
  • Citations: 1
  • Summary: A dermoscopic perspective of this rare presentation of KFSD in an 11-year-old female is reported, which is unusual in females as they are carriers or have milder symptoms.
  • Evidence snippets:
  • Snippet 1 (score: 0.589) > Keratosis follicularis spinulosa decalvans: A dermoscopic perspective

[6] KERATOSIS FOLLICULARIS SPINULOSA DECALVANS ASSOCIATED WITH ACNE KELOIDALIS NUCHAE

  • Authors: I. Topal, I. Sahin, Betül Berberoğlu, M. Ozer
  • Year: 2014
  • Venue: Our Dermatology Online
  • URL: https://www.semanticscholar.org/paper/90f12f1ac8159640bea81d0b3808104d30f9bf3f
  • DOI: 10.7241/OURD.20142.36
  • Summary: The case of a patient with KFSD associated with AKN, a syndrome of chronic folliculitis that manifests as follicular-based pustules and papules on the occipital region of the scalp, that were now manifesting as cicatricial alopecia is reported.
  • Evidence snippets:
  • Snippet 1 (score: 0.585) > KERATOSIS FOLLICULARIS SPINULOSA DECALVANS ASSOCIATED WITH ACNE KELOIDALIS NUCHAE
  • Snippet 2 (score: 0.541) > In 1905, Lamaris first described keratosis follicularis spinulosa decalvans (KFSD) as ichthyosis follicularis [1]. Later, Siemens provided more detailed phenotypic characteristics of the disease and first used the term KFSD in 1926 [2]. This condition is characterized by diffuse keratosis pilaris, cicatricial alopecia, and photophobia and is associated with cutis laksa, deafness, aminoaciduria, mental retardation, and atopy [3]. However, only very rarely has acne keloidalis nuchae (AKN) been associated with KFSD in the literature. Herein, we report a case of KFSD with acne keloidalis lesions.

[7] Keratosis follicularis spinulosa decalvans in a female.

  • Authors: F. Sequeira, E. Jayaseelan
  • Year: 2011
  • Venue: Indian journal of dermatology, venereology and leprology
  • URL: https://www.semanticscholar.org/paper/85620e7ed4d35ee6a80f0b34556144ef1680c8fa
  • DOI: 10.4103/0378-6323.79708
  • PMID: 21508573
  • Citations: 14
  • Influential citations: 1
  • Summary: This work describes this not so common entity of KFSD in a nine year old female child and describes how it differs between males and females.
  • Evidence snippets:
  • Snippet 1 (score: 0.573) > Keratosis follicularis spinulosa decalvans (KFSD), is a rare follicular syndrome associated with widespread keratosis pilaris and progressive scarring alopecia. This genodermatoses often starts at infancy or early childhood with an X-linked mode of inheritance. Males are predominantly affected and females frequently show no disease or only a mild form. We describe this not so common entity of KFSD in a nine year old female child.

[8] MBTPS2, a membrane bound protease, underlying several distinct skin and bone disorders

  • Authors: Natarin Caengprasath, T. Theerapanon, T. Porntaveetus, V. Shotelersuk
  • Year: 2021
  • Venue: Journal of Translational Medicine
  • URL: https://www.semanticscholar.org/paper/fe9d86c9d7756cfdcf3a0bb128efcbedc053fdff
  • DOI: 10.1186/s12967-021-02779-5
  • PMID: 33743732
  • PMCID: 7981912
  • Citations: 24
  • Influential citations: 1
  • Summary: The biological role of MBTPS2 in development is presented, its mutations and implicated disorders are summarized, and outstanding unanswered questions are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.555) > Keratosis follicularis spinulosa decalvans (KFSD, MIM #308800) is a rare hereditary disorder of keratinization recognized by widespread hyperkeratotic follicular papules [87]. First described in 1926, the disorder is often presented at infancy or early childhood with an X-linked pattern of inheritance, though sporadic cases or cases inherited in an autosomal dominant fashion have been reported [88][89][90][91][92]. Some affected individuals exhibit extensive keratosis pilaris-like papules, as well as facial erythema, hypotrichosis, and cicatricial alopecia of the scalp, eyebrows, and eyelashes. Extracutaneous features include photophobia, keratitis, blepharitis, and enamel hypoplasia. As the phenotypes of this disorder considerably simulates IFAP, KFSD is sometimes considered as a 'milder form of IFAP, however, this disorder can be distinguished from IFAP via the nature of alopecia, which is progressive with variable degrees of inflammatory change leading to scarring in KFSD. > Mutations in MBTPS2 have been identified as one of the causative genes of KFSD. Alike mutations leading to the IFAP triad, mutations underlying KFSD lie within the TM domains of MBTPS2. In three unrelated families, a missense mutation in MBTPS2 (p.N508S) was identified in affected males displaying mild phenotypes [87]. Following this, two independent studies reported a Chinese and a Swedish family in which the same mutation segregated with mild phenotypes of KFSD [79,92]. The position of this recurrent mutation was mapped to be at the COOH-terminal end of MBTPS2 and a genotype-phenotype effect specific to MBTPS2 mutation was speculated (Fig. 4).

[9] MBTPS2, a membrane bound protease, underlying several distinct skin and bone disorders

  • Authors: Natarin Caengprasath, T. Theerapanon, T. Porntaveetus, V. Shotelersuk
  • Year: 2021
  • Venue: Journal of Translational Medicine
  • URL: https://www.semanticscholar.org/paper/34290316ee50bf6a7e751ca593aec8e9d6a105f0
  • DOI: 10.1186/s12967-021-02779-5
  • Summary: The biological role of MBTPS2 in development is presented, its mutations and implicated disorders are summarized, and outstanding unanswered questions are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.555) > Keratosis follicularis spinulosa decalvans (KFSD, MIM #308800) is a rare hereditary disorder of keratinization recognized by widespread hyperkeratotic follicular papules [87]. First described in 1926, the disorder is often presented at infancy or early childhood with an X-linked pattern of inheritance, though sporadic cases or cases inherited in an autosomal dominant fashion have been reported [88][89][90][91][92]. Some affected individuals exhibit extensive keratosis pilaris-like papules, as well as facial erythema, hypotrichosis, and cicatricial alopecia of the scalp, eyebrows, and eyelashes. Extracutaneous features include photophobia, keratitis, blepharitis, and enamel hypoplasia. As the phenotypes of this disorder considerably simulates IFAP, KFSD is sometimes considered as a 'milder form of IFAP, however, this disorder can be distinguished from IFAP via the nature of alopecia, which is progressive with variable degrees of inflammatory change leading to scarring in KFSD. > Mutations in MBTPS2 have been identified as one of the causative genes of KFSD. Alike mutations leading to the IFAP triad, mutations underlying KFSD lie within the TM domains of MBTPS2. In three unrelated families, a missense mutation in MBTPS2 (p.N508S) was identified in affected males displaying mild phenotypes [87]. Following this, two independent studies reported a Chinese and a Swedish family in which the same mutation segregated with mild phenotypes of KFSD [79,92]. The position of this recurrent mutation was mapped to be at the COOH-terminal end of MBTPS2 and a genotype-phenotype effect specific to MBTPS2 mutation was speculated (Fig. 4).

[10] Keratosis Follicularis Spinulosa Decalvans: A Report of Three Cases

  • Authors: Dipali D Malvankar, Sarvajnamurthy A Sacchidanand
  • Year: 2015
  • Venue: International Journal of Trichology
  • URL: https://www.semanticscholar.org/paper/32223071aaac64612e2c7b20832a274653932a21
  • DOI: 10.4103/0974-7753.167461
  • PMID: 26622157
  • PMCID: 4639957
  • Citations: 13
  • Influential citations: 1
  • Summary: Three cases of this rare disorder affecting the hair follicles characterized by scarring alopecia of the scalp, eyebrows, and axillae are reported including one in a female.
  • Evidence snippets:
  • Snippet 1 (score: 0.552) > Keratosis follicularis spinulosa decalvans is a disorder affecting the hair follicles characterized by scarring alopecia of the scalp, eyebrows, and axillae, sometimes associated with photophobia and keratoderma. Being X-linked, it is more commonly seen in males but can be rarely seen in females also. We report three cases of this rare disorder including one in a female.

[11] Keratosis Follicularis Spinulosa Decalvans: Diagnosis and TherapeuticEvaluation.

  • Authors: K. Gharib, M. Khater, M. Nasr, M. Soliman, Ahmed Abdelshafi
  • Year: 2015
  • Venue: journal of Clinical Case Reports
  • URL: https://www.semanticscholar.org/paper/ffb7481079e1eef36bbe53db8333a3115214383d
  • DOI: 10.4172/2165-7920.1000532
  • Citations: 2
  • Summary: A family of two siblings of KFSD, boy had nine years and girl had five years old is presented, both of them carriers of this genodermatosis.
  • Evidence snippets:
  • Snippet 1 (score: 0.547) > Keratosis Follicularis Spinulosa Decalvans (KFSD) is an X-linked genodermatosis characterized by scarring alopecia and follicular hyperkeratosis. This condition mainly affects males with females being carriers and will have milder symptoms. We present a family of two siblings of KFSD, boy had nine years and girl had five years old. This genodermatosis often starts at infancy or early childhood. Keratosis pilaris atrophicans (KPA) is the umbrella term for a group of three rare and distinct clinical entities representing the scarring types of keratosis pilaris [1]. > Three categories of KPA include: Keratosis pilaris atrophicans faciei (KPAF), Atrophoderma Vermiculatum (AV) and Keratosis Follicularis Spinulosa Decalvans (KFSD). They have the following features in common: keratotic follicular papules, nonpurulent inflammation of variable degree, and atrophic end stages characterized by irreversible hair loss and/or atrophic depressions similar to pitted scars [2]. > KFSD simulates the ichthyosis follicularis alopecia photophobia (IFAP) syndrome. The latter is characterized by non-scarring alopecia, extensive keratosis piliaris, severe photophobia and corneal dystrophy. The presence of scarring alopecia in our patients favors the diagnosis of KFSD over the IFAP syndrome. The other follicular conditions that it needs to be differentiated from are lichen planopilaris and lichen spinulosus [3].
  • Snippet 2 (score: 0.531) > Keratosis Follicularis Spinulosa Decalvans (KFSD) is an X-linked > genodermatosis characterized by scarring alopecia and follicular > hyperkeratosis. This condition mainly affects males with females being > carriers and will have milder symptoms. We present a family of two > siblings of KFSD, boy had nine years and girl had five years old. This > genodermatosis often starts at infancy or early childhood. Keratosis > pilaris atrophicans (KPA) is the umbrella term for a group of three rare > and distinct clinical entities representing the scarring types of keratosis > pilaris.

[12] A rare presentation of keratosis follicularis spinulosa decalvans in female twins

  • Authors: R. Chauhan, Saumya Sankhwar, R. Tripathi, S. Pandey
  • Year: 2018
  • Venue: Indian Journal of Dermatology, Venereology and Leprology
  • URL: https://www.semanticscholar.org/paper/32b806a618ae76ef3afc69eecac3dd82bc212265
  • DOI: 10.4103/ijdvl.IJDVL_524_16
  • PMID: 28928337
  • Citations: 4
  • Summary: A 9‐year-old pair of monozygotic twin sisters, born of spontaneous, full‐term normal vaginal delivery, visited the dermatology outpatient department of Sir Sunderlal Hospital, Banaras Hindu University, Varanasi, with the absence of body and scalp hair since birth.
  • Evidence snippets:
  • Snippet 1 (score: 0.536) > Sir, A 9-year-old pair of monozygotic twin sisters, born of spontaneous, full-term normal vaginal delivery, visited the dermatology outpatient department of Sir Sunderlal Hospital, Banaras Hindu University, Varanasi, with the absence of body and scalp hair since birth. There was no history of consanguinity in parents. Parents were using various homemade remedies for the condition, on-and-off, including ayurvedic treatment, since 1 year of age. Some hairs appeared on the scalp one year later and they were persistent [Figures 1 and 2a]. Examination revealed small, discrete, spiny papules with follicular plugging, present on normal looking skin on the body [Figure 2b]. Oral mucosa, teeth, nails, palms and soles were found to be normal. There was no history of photophobia. Ophthalmic examination revealed no abnormal findings. Routine hematological and other laboratory studies were within normal limits. Hair microscopy was done to rule out hair shaft defects. > Histopathological examination of the hairy areas such as the scalp and extensor aspect of the left forearm showed sparse superficial perivascular and periappendageal lymphocytic infiltrates with no epidermal changes. Some of the follicular infundibula were dilated and plugged with orthokeratotic corneocytes while others showed mild spongiosis. There was dense perifollicular fibroplasia in some follicles and the terminal follicles were reduced in number on the scalp skin [Figures 3 and 4]. Based on these clinical and histopathological findings, these cases were diagnosed as keratosis follicularis spinulosa decalvans. > Keratosis follicularis spinulosa decalvans is a rare, X-linked, hereditary disorder of keratinization, characterized by the involvement of the skin and eyes. Keratosis follicularis spinulosa decalvans was first described as an X-linked dominant disorder. 1 However, in some cases, an autosomal dominant and sporadic inheritance have also been reported.

[13] Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2

  • Authors: E. Aten, Lisa C. Brasz, D. Bornholdt, Ingeborg B. Hooijkaas, M. Porteous et al.
  • Year: 2010
  • Venue: Human Mutation
  • URL: https://www.semanticscholar.org/paper/52a52d183695a401b3c4273ab61a9745d364b58e
  • DOI: 10.1002/humu.21335
  • PMID: 20672378
  • Citations: 72
  • Influential citations: 4
  • Summary: It is postulated that both phenotypes of KFSD are in the spectrum of one genetic disorder with a partially overlapping phenotype, and MBTPS2 is required for cleavage of sterol regulatory element‐binding proteins (SREBPs).
  • Evidence snippets:
  • Snippet 1 (score: 0.522) > Keratosis Follicularis Spinulosa Decalvans (KFSD) is a rare genetic disorder characterized by development of hyperkeratotic follicular papules on the scalp followed by progressive alopecia of the scalp, eyelashes, and eyebrows. Associated eye findings include photophobia in childhood and corneal dystrophy. Due to the genetic and clinical heterogeneity of similar disorders, a definitive diagnosis of KFSD is often challenging. Toward identification of the causative gene we reanalyzed a large Dutch KFSD family. SNP arrays (1 M) redefined the locus to a 2.9‐Mb region at Xp22.12–Xp22.11. Screening of all 14 genes in the candidate region identified MBTPS2 as the candidate gene carrying a c.1523A>G (p.Asn508Ser) missense mutation. The variant was also identified in two unrelated X‐linked KFSD families and cosegregated with KFSD in all families. In symptomatic female carriers, skewed X‐inactivation of the normal allele matched with increased severity of symptoms. MBTPS2 is required for cleavage of sterol regulatory element‐binding proteins (SREBPs). In vitro functional expression studies of the c.1523A>G mutation showed that sterol responsiveness was reduced by half. Other missense mutations in MBTPS2 have recently been identified in patients with IFAP syndrome. We postulate that both phenotypes are in the spectrum of one genetic disorder with a partially overlapping phenotype. Hum Mutat 31:1–9, 2010. © 2010 Wiley‐Liss, Inc.

[14] Keratosis Follicularis Spinulosa Decalvans Associated With Woolly Hair: A Case Report

  • Authors: Reem Brashi, Raghad E. Saleh, E. Alsulami, A. Niyazi, Maria AlSulami et al.
  • Year: 2024
  • Venue: Cureus
  • URL: https://www.semanticscholar.org/paper/de046f44f473bf66fff17faf8b284c0de31d61c8
  • DOI: 10.7759/cureus.65668
  • PMID: 39205768
  • PMCID: 11354409
  • Citations: 1
  • Summary: The case of a 14-year-old boy who presented with a history of abnormal hair since birth, who was diagnosed with KFSDX associated with woolly hair, who did not show up for further treatment during the follow-up.
  • Evidence snippets:
  • Snippet 1 (score: 0.519) > Keratosis follicularis spinulosa decalvans X-linked (KFSDX) is part of the spectrum of a rare disorder known as keratosis pilaris atrophicans. It has four variants including KFSDX, keratosis pilaris atrophicans faciei (ulerythema ophryogenes), atrophoderma vermiculata, and keratosis follicularis spinulosa decalvans (KFSD). The latter is an autosomal dominant condition also known as folliculitis spinulosa decalvans (FSD) [1]. These disorders are characterized by inflammatory keratotic follicular papules that later end in atrophy causing cicatricial alopecia [2]. KFSDX is an X-linked inherited disorder that affects the scalp, eyebrows, eyelashes, cheeks, nose, neck, dorsal hands, and fingers, whereas, in ulerythema ophryogenes, the lateral eyebrows, temples, cheeks, and forehead are affected [2]. In atrophoderma vermiculata, the cheeks, neck, and limbs are affected [3]. KFSD or FSD presents with follicular pustules on the scalp along with other features of KFSDX [3]. KFSDX is an X-linked recessive condition caused by a mutation in the membranebound transcription factor protease site 2 (MBTPS2) gene [4]. The onset of KFSDX starts during childhood with follicular keratotic papules. At puberty, the scarring alopecia develops. Woolly hair has been reported with KFSDX. The patient described in this case showed this very rare association of woolly hair with KFSDX.

Notes

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