Zlotogora–Ogur Syndrome (CLPED1) — Comprehensive Disease Characteristics Report

Executive summary

Zlotogora–Ogur syndrome is now generally considered part of cleft lip/palate–ectodermal dysplasia syndrome 1 (CLPED1) (also historically called Margarita Island ectodermal dysplasia / Margarita Island type), a rare autosomal recessive disorder characterized by orofacial clefting, ectodermal dysplasia (hair/skin/teeth/nails/sweat gland abnormalities), and limb anomalies (syndactyly), with variable neurodevelopmental involvement. The condition is caused by biallelic loss-of-function variants in PVRL1 (NECTIN1), encoding the cell–cell adhesion molecule nectin-1. (suzuki2000mutationsofpvrl1 pages 1-1, zlotogora1994syndactylyectodermaldysplasia pages 2-3, suzuki2000mutationsofpvrl1 pages 1-3, yoshida2015novelhomozygousmutation pages 1-3)

1. Disease information

1.1 Disease overview (definition)

Clinically, the syndrome was delineated as a pleiotropic association of cleft lip/palate, syndactyly, ectodermal dysplasia, and (in some reports) psychomotor retardation/intellectual disability. A widely cited clinical synthesis reports: “The summary of the clinical manifestations is based on 31 patients affected with the syndrome observed from the age of 4 months to 65 years”. (zlotogora1994syndactylyectodermaldysplasia pages 1-2)

Molecularly, the disorder corresponds to autosomal recessive cleft lip/palate–ectodermal dysplasia (CLPED1) due to PVRL1/NECTIN1 mutations. (suzuki2000mutationsofpvrl1 pages 1-1, suzuki2000mutationsofpvrl1 pages 1-3)

1.2 Key identifiers

• OMIM (preferred, molecular-era): 225060 is used for CLPED1 / Margarita Island type in later reviews and tables. (visinoni2009ectodermaldysplasiasclinical pages 2-3, ganske2021cleftlipand pages 1-2)
• OMIM (historical / inconsistent in older literature): Older sources cite MIM 225000 / 22500 / 225060 for overlapping clinical entities; an ED review notes reassignment of the former Zlotogora–Ogur number. (zlotogora1994syndactylyectodermaldysplasia pages 3-4, visinoni2009ectodermaldysplasiasclinical pages 2-3)
• Gene: PVRL1 (NECTIN1) at 11q23.3. (suzuki2000mutationsofpvrl1 pages 1-1, ganske2021cleftlipand pages 1-2)
• MONDO / MeSH / ICD-10/ICD-11 / Orphanet: Not identified within the retrieved evidence set; mapping should be confirmed via MONDO/Orphanet/MeSH/ICD registries outside this corpus.

1.3 Synonyms and alternative names

Commonly used names in the literature include: * Zlotogora–Ogur syndrome * Syndactyly, ectodermal dysplasia, and cleft lip/palate * Cleft lip/palate–ectodermal dysplasia syndrome * CLPED1 * Margarita Island ectodermal dysplasia / Margarita Island type These synonym relationships are made explicit in molecular-era CLPED1 work and ED reviews. (suzuki2000mutationsofpvrl1 pages 1-1, visinoni2009ectodermaldysplasiasclinical pages 2-3, ganske2021cleftlipand pages 1-2)

1.4 Evidence source type (patient-level vs aggregated)

Evidence is derived from: * Patient-level case reports/series (human clinical) describing multiple affected families and syndromic features (rodini1990autosomalrecessiveectodermal pages 3-4, rodini1990autosomalrecessiveectodermal pages 1-3) * Aggregated clinical synthesis (human clinical summary of multiple reports; 31 cases across wide age range) (zlotogora1994syndactylyectodermaldysplasia pages 1-2) * Molecular genetics (human genetic studies defining PVRL1/NECTIN1 as causal) (suzuki2000mutationsofpvrl1 pages 1-1, suzuki2000mutationsofpvrl1 pages 1-3, yoshida2015novelhomozygousmutation pages 1-3) * Experimental model systems (mouse/in vitro) supporting a nectin–afadin developmental mechanism relevant to palate/periderm biology (lough2020disruptionofthe pages 1-3, lough2020disruptionofthe pages 3-5)

2. Etiology

2.1 Disease causal factors

Primary cause: biallelic pathogenic variants in PVRL1 (NECTIN1), encoding nectin-1, a cell–cell adhesion molecule. * Molecular definition: CLPED1 is described as an “autosomal recessive CL/P-ectodermal dysplasia (CLPED1; previously ED4)” and the locus is identified as PVRL1, “encoding nectin-1”. (suzuki2000mutationsofpvrl1 pages 1-1)

2.2 Risk factors

Genetic risk factors (causal)

• Autosomal recessive inheritance is supported by repeated parental consanguinity in reported families: “The occurrence of consanguinity in the 3 reported families is consistent with autosomal recessive inheritance.” (rodini1990autosomalrecessiveectodermal pages 3-4)
• Multiple families show affected individuals homozygous for pathogenic PVRL1 alleles with heterozygous parents: “In each case the affected patients were homozygous and their parents were heterozygous for the mutant alleles.” (suzuki2000mutationsofpvrl1 pages 1-3)

Environmental risk factors

No established environmental risk factors for CLPED1/Zlotogora–Ogur syndrome were identified in the retrieved evidence.

2.3 Protective factors

No genetic or environmental protective factors were identified in the retrieved evidence.

2.4 Gene–environment interactions

No gene–environment interaction evidence was identified in the retrieved corpus.

3. Phenotypes

3.1 Core phenotype spectrum (human)

Across the clinical synthesis and primary reports, major features include: * Orofacial clefting: “Cleft lip/palate is present in most patients.” (zlotogora1994syndactylyectodermaldysplasia pages 1-2) * Syndactyly: “Cutaneous syndactyly is frequently present in fingers 2-3-4” and “In the feet syndactyly of toes 2-3 is usually present.” (zlotogora1994syndactylyectodermaldysplasia pages 1-2) * Ectodermal dysplasia: sparse/short hair with structural defects (“pili torti” / “kinky hair”), dental anomalies, nail anomalies, hypohidrosis, and progressive palmoplantar hyperkeratosis. (zlotogora1994syndactylyectodermaldysplasia pages 1-2, zlotogora1994syndactylyectodermaldysplasia pages 2-3) * Neurodevelopment: variable impairment; “Mental status may be impaired” and family-to-family differences were noted. (zlotogora1994syndactylyectodermaldysplasia pages 1-2, zlotogora1994syndactylyectodermaldysplasia pages 2-3)

The syndrome demonstrates marked variable expressivity: “The variability of the syndrome is evident…”. (zlotogora1994syndactylyectodermaldysplasia pages 1-2)

3.2 Phenotype characteristics (onset, severity, progression, frequency)

• Onset: structural anomalies (clefting, syndactyly) are congenital. (rodini1990autosomalrecessiveectodermal pages 1-3)
• Progression: palmoplantar hyperkeratosis is progressive, with specific appearance in childhood in at least one case. (zlotogora1994syndactylyectodermaldysplasia pages 1-2)
• Neurodevelopmental severity: ranges from normal cognition to intellectual disability depending on family/allele context. (zlotogora1994syndactylyectodermaldysplasia pages 2-3)
• Mortality: some sibships include neonatal/early childhood deaths of presumed affected individuals; “Some of the affected children died neonatally or at a young age” with cause “unknown.” (zlotogora1994syndactylyectodermaldysplasia pages 2-3)

3.3 Quality-of-life impact

Formal QoL instruments (EQ-5D/SF-36/PROMIS) were not identified in the retrieved evidence for CLPED1 specifically. However, the phenotype implies significant functional burden (feeding/speech/hearing/dental/dermatologic and surgical needs).

3.4 Suggested HPO terms

A curated phenotype-to-HPO mapping table is provided in Artifact-01.

Table: This table summarizes the core and variably reported phenotypes of Zlotogora-Ogur syndrome / CLPED1, with suggested HPO mappings, typical timing, and brief notes on expressivity. It is useful for knowledge-base curation and phenotype-to-ontology annotation.

4. Genetic / molecular information

4.1 Causal gene

PVRL1 (NECTIN1) encodes nectin-1, an immunoglobulin superfamily adhesion protein. * Molecular identification: “which we identify as PVRL1, encoding nectin-1, an immunoglobulin (Ig)-related transmembrane cell-cell adhesion molecule.” (suzuki2000mutationsofpvrl1 pages 1-1)

4.2 Pathogenic variants (examples with evidence)

From the gene-discovery study and subsequent case report: * Trp185Ter (W185X): “At codon Trp185 (TGG), a homozygous nonsense mutation (TAG) was found…” (suzuki2000mutationsofpvrl1 pages 1-3) * Frameshift at codon 185 (single-base deletion at Trp185): “a homozygous frameshift (TG–)…” (suzuki2000mutationsofpvrl1 pages 1-3) * Frameshift at Gly323 (single-base duplication): “At codon Gly323 (GGT), a homozygous frameshift (GGTT)…” (suzuki2000mutationsofpvrl1 pages 1-3) * c.400C>T (p.Arg134*): “Novel homozygous mutation, c.400C>T (p.Arg134*), in the PVRL1 gene…” (yoshida2015novelhomozygousmutation pages 1-3)

4.3 Functional consequences

The truncating variants are predicted to abrogate nectin-1’s intracellular interactions and adhesion signaling. * Mechanism statement: the truncating mutations “would truncate…nectin-1…thereby abolishing interaction with 1-afadin and thus abrogating…cell-cell adhesion.” (suzuki2000mutationsofpvrl1 pages 1-3)

4.4 Modifier genes / epigenetics / chromosomal abnormalities

No validated modifier genes or epigenetic signatures were identified in the retrieved CLPED1-specific evidence. Karyotype was reported normal in a classic clinical family. (rodini1990autosomalrecessiveectodermal pages 3-4)

5. Environmental information

No specific environmental/lifestyle/infectious contributors were identified in the retrieved evidence; CLPED1 is primarily a monogenic Mendelian disorder in the reviewed sources.

6. Mechanism / pathophysiology

6.1 Current understanding (nectin–afadin axis in epithelial morphogenesis)

A convergent theme is disruption of adherens junction formation and epithelial adhesion in craniofacial and ectodermal tissues.

• PVRL1/NECTIN1 is a cell–cell adhesion molecule; truncating variants disrupt interaction with afadin (the actin-binding scaffolding partner). (suzuki2000mutationsofpvrl1 pages 1-3)
• PVRL1 expression during development is reported in tissues relevant to CLPED1 phenotypes (palatal shelves, tooth buds, skin epithelium). (suzuki2000mutationsofpvrl1 pages 1-3)

6.2 Causal chain (conceptual)

1. Biallelic PVRL1 loss-of-function → truncated nectin-1 lacking proper intracellular signaling/anchoring. (suzuki2000mutationsofpvrl1 pages 1-3, yoshida2015novelhomozygousmutation pages 1-3)
2. Loss of nectin–afadin linkage → impaired adherens-junction assembly/maintenance and epithelial cohesion in developing palate/periderm and ectodermal appendage primordia. (suzuki2000mutationsofpvrl1 pages 1-3, lough2020disruptionofthe pages 3-5)
3. Developmental morphogenesis failures → palatal shelf fusion defects (clefting) and ectodermal derivative abnormalities (hair/teeth/nails/sweat glands), plus limb webbing/syndactyly. (zlotogora1994syndactylyectodermaldysplasia pages 1-2, rodini1990autosomalrecessiveectodermal pages 1-3)

6.3 Pathways and ontology suggestions

• Cell adhesion / adherens junction organization: GO:0034332 was invoked in 2024 protein-network analyses connecting afadin and nectins to adherens junction organization. (awotoye2024damagingmutationsin pages 9-13)
• Additional plausible GO terms for curation (not directly asserted in the texts but aligned with the described mechanism): “cell-cell adhesion” and “adherens junction assembly.”

6.4 Recent developments (prioritize 2023–2024)

Recent work does not primarily expand CLPED1 patient series, but refines mechanistic understanding of the same junctional module:

(a) 2023 mechanobiology (preprint; protein–protein interaction under force): Afadin PDZ–nectin-1 binding exhibits force-stabilized behavior. The preprint reports short solution lifetimes (“bond lifetimes of 1.2…s for the nectin-1…ICDs”) and concludes “PDZ domains can serve as force-responsive mechanical anchors at cell-cell adhesion complexes.” (vachharajani2023pdzdomainsfrom pages 1-3)

(b) 2024 human genetics and network biology (peer-reviewed): AFDN (afadin) damaging variants were proposed to contribute to nonsyndromic cleft risk, with analyses highlighting AFADIN’s direct interactions with nectins and a reported association of afadin–nectin interaction networks with CLPED biology (FDR reported in the paper). (awotoye2024damagingmutationsin pages 13-16, awotoye2024damagingmutationsin pages 9-13)

Evidence-type labeling: * (a) computational + single-molecule biophysics; preprint (bioRxiv) (vachharajani2023pdzdomainsfrom pages 1-3) * (b) human genetics cohorts + computational structural/network analyses; peer-reviewed primary research (awotoye2024damagingmutationsin pages 13-16, awotoye2024damagingmutationsin pages 9-13)

7. Anatomical structures affected

Based on the phenotype profile: * Craniofacial: lip and palate (UBERON: lip/palate structures), dental primordia/teeth. (zlotogora1994syndactylyectodermaldysplasia pages 1-2, zlotogora1994syndactylyectodermaldysplasia pages 2-3) * Integumentary system: skin, hair follicles, sweat glands, nails. (zlotogora1994syndactylyectodermaldysplasia pages 1-2, zlotogora1994syndactylyectodermaldysplasia pages 2-3) * Limbs: fingers/toes (cutaneous syndactyly). (zlotogora1994syndactylyectodermaldysplasia pages 1-2) * Potential additional systems: auditory system (hearing loss), renal/genitourinary anomalies variably. (rodini1990autosomalrecessiveectodermal pages 3-4)

Cell types (CL suggestions) most directly implicated by the mechanism include epithelial cells of palatal shelves and epidermis/periderm (supported mechanistically by mouse epithelial perturbation studies). (lough2020disruptionofthe pages 3-5)

Subcellular components (GO Cellular Component) implicated: adherens junction complexes and associated cytoskeleton (supported conceptually; afadin/nectin are junctional/cytoskeletal linkers). (suzuki2000mutationsofpvrl1 pages 1-3, vachharajani2023pdzdomainsfrom pages 1-3)

8. Temporal development (onset and progression)

• Congenital onset of clefting and syndactyly is typical. (rodini1990autosomalrecessiveectodermal pages 1-3)
• Progressive dermatologic manifestations can emerge and worsen with age; palmoplantar hyperkeratosis is described as progressive, and alopecia can develop later in life in some individuals. (zlotogora1994syndactylyectodermaldysplasia pages 1-2)
• Neurodevelopmental course is variable (family-dependent). (zlotogora1994syndactylyectodermaldysplasia pages 2-3)

9. Inheritance and population

9.1 Inheritance

Autosomal recessive inheritance is consistently supported: * “The syndrome is inherited as an autosomal recessive trait.” (zlotogora1994syndactylyectodermaldysplasia pages 2-3) * Multiple reports cite parental consanguinity: “In all the families reported up to now the parents of the affected children were related.” (zlotogora1994syndactylyectodermaldysplasia pages 2-3)

9.2 Epidemiology

Syndrome-specific prevalence/incidence was not identified in the retrieved evidence.

Available quantitative proxies: * A clinical synthesis aggregated 31 patients across reports. (zlotogora1994syndactylyectodermaldysplasia pages 1-2) * In a large ED clinic cohort (not CLPED1-specific), 24/170 (14%) ED patients had CL/P. (ganske2021cleftlipand pages 2-4)

9.3 Population genetics / founder effects

Repeated consanguinity suggests founder effects in reported families. (zlotogora1994syndactylyectodermaldysplasia pages 2-3) Carrier frequency and population allele frequencies for specific PVRL1 pathogenic alleles were not available in the retrieved evidence.

10. Diagnostics

10.1 Clinical recognition

A practical clinical definition is based on co-occurrence of: 1) CL/P, 2) ectodermal abnormalities (hair/teeth/nails/sweating/skin), 3) syndactyly.

In the ED-spectrum framing, “A diagnosis of ED requires defects in two or more ectodermal derivatives…”. (ganske2021cleftlipand pages 1-2)

10.2 Differential diagnosis

Zlotogora (1994) highlights distinction from EEC syndrome, noting differences in inheritance and features; it suggests palmoplantar hyperkeratosis in older patients can help distinguish the disorders. (zlotogora1994syndactylyectodermaldysplasia pages 2-3)

10.3 Genetic testing strategy (real-world implementation)

Evidence-supported approach: * Sequence PVRL1 (NECTIN1) to confirm CLPED1 in suspected cases, especially in consanguineous families. (yoshida2015novelhomozygousmutation pages 1-3) * Yoshida et al. performed direct sequencing of PVRL1 and family testing; parents were heterozygous carriers. (yoshida2015novelhomozygousmutation pages 1-3)

10.4 Ancillary testing

In the molecularly confirmed Japanese case, the work-up included: * physiologic testing for hypohidrosis (sympathetic skin response) * microscopy/SEM for hair-shaft abnormalities * dermatologic evaluation and management for dermatitis. (yoshida2015novelhomozygousmutation pages 1-3)

11. Outcome / prognosis

Long-term prognosis is variable and not captured in prospective natural history studies in the retrieved corpus.

Observed outcomes include: * Survival into adulthood (clinical synthesis includes patients up to 65 years). (zlotogora1994syndactylyectodermaldysplasia pages 1-2) * Developmental disability can persist when present (classic family with affected brothers). (rodini1990autosomalrecessiveectodermal pages 1-3) * Neonatal/early childhood deaths reported in some pedigrees, with unclear attribution. (zlotogora1994syndactylyectodermaldysplasia pages 2-3)

12. Treatment

No disease-modifying molecular therapy exists in the retrieved evidence; management is supportive and surgical.

12.1 Surgical and interventional

• Cleft lip/palate repair: historical clinical photos note repaired cleft lip; modern ED-CL/P care follows standard cleft protocols. (zlotogora1994syndactylyectodermaldysplasia pages 1-2, ganske2021cleftlipand pages 2-4)
• Syndactyly repair: surgical scars were described in a molecularly confirmed case, indicating real-world correction. (yoshida2015novelhomozygousmutation pages 1-3)

12.2 Supportive care

• Dermatologic treatment for dermatitis/eczema from infancy was reported in a molecularly confirmed case. (yoshida2015novelhomozygousmutation pages 1-3)
• ED-CL/P cohorts emphasize dental, otologic, ocular, and respiratory comorbidity management (though not specific to CLPED1 alone). (ganske2021cleftlipand pages 4-5, ganske2021cleftlipand pages 5-6)

12.3 Treatment outcomes and statistics (recent clinical data)

While not CLPED1-specific, ED-CL/P cohort outcomes provide real-world expectations for syndromic cleft care: * In an ED cohort, 3/9 (33%) older bilateral cases had velopharyngeal insufficiency; palatal fistula occurred (count reported). (ganske2021cleftlipand pages 2-4) * Patients may have perioperative respiratory complications requiring ICU monitoring. (ganske2021cleftlipand pages 5-6)

12.4 MAXO term suggestions

• Cleft lip repair / cleft palate repair (MAXO: surgical repair of cleft lip/palate)
• Syndactyly surgical correction
• Genetic counseling
• Dental rehabilitation (prosthodontic/orthodontic management for hypodontia)
• Dermatologic therapy for eczema/keratoderma

12.5 Clinical trials

No CLPED1/Zlotogora–Ogur–specific therapeutic trials were identified; trials returned by broad searches primarily involved NECTIN4 oncology targets and are not relevant to treating CLPED1. (clinical-trials tool results; no relevant CLPED1 trials)

13. Prevention

Primary prevention is not applicable in the usual public-health sense for a monogenic Mendelian disorder. Prevention strategies are genetic: * Carrier testing and reproductive counseling in affected families (supported by AR inheritance and consanguinity patterns). (zlotogora1994syndactylyectodermaldysplasia pages 2-3) * Prenatal / preimplantation genetic testing is logically enabled when familial PVRL1 pathogenic variants are known (inference from established causality; family-based heterozygosity demonstrated). (suzuki2000mutationsofpvrl1 pages 1-3, yoshida2015novelhomozygousmutation pages 1-3)

14. Other species / natural disease

No naturally occurring veterinary analogs were identified in the retrieved evidence.

15. Model organisms

Experimental systems show that disruption of the nectin–afadin axis can produce palatal fusion defects in mouse.

• Development 2020 supplementary evidence shows that epithelial afadin loss via in utero lentiviral Cre is sufficient to cause cleft palate, while a later keratin promoter Cre approach was insufficient in that context (“Afdn knockout via lenti-Cre is suffient to cause CP, while K14-Cre is insufficient”). (lough2020disruptionofthe pages 1-3)
• Dual knockdown of Nectin1 and Nectin4 produced delays in palatal shelf elevation and residual epithelial seam, and periderm abnormalities, supporting periderm/epithelium contributions to clefting. (lough2020disruptionofthe pages 3-5)

These models support a mechanistic bridge from PVRL1/NECTIN1 loss to impaired epithelial adhesion during palatogenesis.

Structured identifier summary (artifact)

Table: This table summarizes the main disease names, OMIM identifier history, inheritance, causal gene, and landmark references for Zlotogora-Ogur syndrome/CLPED1. It is useful for reconciling older clinical nomenclature with the later molecular definition based on PVRL1/NECTIN1.

Notes on evidence gaps (important for knowledge base curation)

• MONDO/MeSH/ICD/Orphanet identifiers were not retrieved here and should be cross-mapped externally.
• Syndrome-specific prevalence/incidence, carrier frequency, and variant population allele frequencies were not available in the retrieved full texts.
• Standardized diagnostic criteria (beyond phenotype and genetic confirmation) and formal clinical guidelines specific to CLPED1 were not identified.

Key references (with publication dates and URLs)

• Rodini & Richieri-Costa. Am J Med Genet. Aug 1990. https://doi.org/10.1002/ajmg.1320360420 (rodini1990autosomalrecessiveectodermal pages 1-3)
• Zlotogora. J Med Genet. Dec 1994. https://doi.org/10.1136/jmg.31.12.957 (zlotogora1994syndactylyectodermaldysplasia pages 1-2)
• Suzuki et al. Nat Genet. Aug 2000. https://doi.org/10.1038/78119 (suzuki2000mutationsofpvrl1 pages 1-3)
• Visinoni et al. Am J Med Genet A. Sep 2009. https://doi.org/10.1002/ajmg.a.32864 (visinoni2009ectodermaldysplasiasclinical pages 2-3)
• Yoshida et al. J Dermatol. Jul 2015. https://doi.org/10.1111/1346-8138.12882 (yoshida2015novelhomozygousmutation pages 1-3)
• Ganske et al. Cleft Palate Craniofac J. Aug 2021. https://doi.org/10.1177/1055665620949124 (ganske2021cleftlipand pages 2-4)
• Vachharajani et al. bioRxiv. Oct 2023. https://doi.org/10.1101/2023.09.24.559210 (vachharajani2023pdzdomainsfrom pages 1-3)
• Awotoye et al. Cleft Palate Craniofac J. Nov 2024. https://doi.org/10.1177/10556656221135926 (awotoye2024damagingmutationsin pages 13-16)

References

1. (suzuki2000mutationsofpvrl1 pages 1-1): Koji Suzuki, Diane Hu, Tania Bustos, Joel Zlotogora, Antonio Richieri-Costa, Jill A. Helms, and Richard A. Spritz. Mutations of pvrl1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal dysplasia. Nature Genetics, 25:427-430, Aug 2000. URL: https://doi.org/10.1038/78119, doi:10.1038/78119. This article has 437 citations and is from a highest quality peer-reviewed journal.

2. (zlotogora1994syndactylyectodermaldysplasia pages 2-3): J. Zlotogora. Syndactyly, ectodermal dysplasia, and cleft lip/palate. Journal of Medical Genetics, 31:957-959, Dec 1994. URL: https://doi.org/10.1136/jmg.31.12.957, doi:10.1136/jmg.31.12.957. This article has 30 citations and is from a domain leading peer-reviewed journal.

3. (suzuki2000mutationsofpvrl1 pages 1-3): Koji Suzuki, Diane Hu, Tania Bustos, Joel Zlotogora, Antonio Richieri-Costa, Jill A. Helms, and Richard A. Spritz. Mutations of pvrl1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal dysplasia. Nature Genetics, 25:427-430, Aug 2000. URL: https://doi.org/10.1038/78119, doi:10.1038/78119. This article has 437 citations and is from a highest quality peer-reviewed journal.

4. (yoshida2015novelhomozygousmutation pages 1-3): Kazue Yoshida, Ryota Hayashi, Hideki Fujita, Masaya Kubota, Mai Kondo, Yutaka Shimomura, and Hironori Niizeki. Novel homozygous mutation, c.400c>t (p.arg134*), in the pvrl1 gene underlies cleft lip/palate‐ectodermal dysplasia syndrome in an asian patient. The Journal of Dermatology, 42:715-719, Jul 2015. URL: https://doi.org/10.1111/1346-8138.12882, doi:10.1111/1346-8138.12882. This article has 18 citations.

5. (zlotogora1994syndactylyectodermaldysplasia pages 1-2): J. Zlotogora. Syndactyly, ectodermal dysplasia, and cleft lip/palate. Journal of Medical Genetics, 31:957-959, Dec 1994. URL: https://doi.org/10.1136/jmg.31.12.957, doi:10.1136/jmg.31.12.957. This article has 30 citations and is from a domain leading peer-reviewed journal.

6. (visinoni2009ectodermaldysplasiasclinical pages 2-3): Átila F. Visinoni, Toni Lisboa‐Costa, Nina A.B. Pagnan, and Eleidi A. Chautard‐Freire‐Maia. Ectodermal dysplasias: clinical and molecular review. American Journal of Medical Genetics Part A, 149A:1980-2002, Sep 2009. URL: https://doi.org/10.1002/ajmg.a.32864, doi:10.1002/ajmg.a.32864. This article has 244 citations.

7. (ganske2021cleftlipand pages 1-2): Ingrid M. Ganske, Tim Irwin, Olivia Langa, Joseph Upton, Wen-Hann Tan, and John B. Mulliken. Cleft lip and palate in ectodermal dysplasia. The Cleft Palate-Craniofacial Journal, 58:237-243, Aug 2021. URL: https://doi.org/10.1177/1055665620949124, doi:10.1177/1055665620949124. This article has 11 citations.

8. (zlotogora1994syndactylyectodermaldysplasia pages 3-4): J. Zlotogora. Syndactyly, ectodermal dysplasia, and cleft lip/palate. Journal of Medical Genetics, 31:957-959, Dec 1994. URL: https://doi.org/10.1136/jmg.31.12.957, doi:10.1136/jmg.31.12.957. This article has 30 citations and is from a domain leading peer-reviewed journal.

9. (rodini1990autosomalrecessiveectodermal pages 3-4): Elaine S. O. Rodini and A. Richieri‐Costa. Autosomal recessive ectodermal dysplasia, cleft lip/palate, mental retardation, and syndactyly: the zlotogora-ogur syndrome. American journal of medical genetics, 36 4:473-6, Aug 1990. URL: https://doi.org/10.1002/ajmg.1320360420, doi:10.1002/ajmg.1320360420. This article has 26 citations.

10. (rodini1990autosomalrecessiveectodermal pages 1-3): Elaine S. O. Rodini and A. Richieri‐Costa. Autosomal recessive ectodermal dysplasia, cleft lip/palate, mental retardation, and syndactyly: the zlotogora-ogur syndrome. American journal of medical genetics, 36 4:473-6, Aug 1990. URL: https://doi.org/10.1002/ajmg.1320360420, doi:10.1002/ajmg.1320360420. This article has 26 citations.

11. (lough2020disruptionofthe pages 1-3): Kendall J. Lough, Danielle C. Spitzer, Abby J. Bergman, Jessica J. Wu, Kevin M. Byrd, and Scott E. Williams. Disruption of the nectin-afadin complex recapitulates features of the human cleft lip/palate syndrome clped1. Development, Jan 2020. URL: https://doi.org/10.1242/dev.189241, doi:10.1242/dev.189241. This article has 26 citations and is from a domain leading peer-reviewed journal.

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