Ectodermal dysplasia

Gene: NECTIN4

Green List (high evidence)

PMID: 20691405 Brancati et al. 2010
Family A - 4 affected siblings, Algerian origins, first-cousin parents; c.851G>A (p.Arg284Gln), homozygous; phenotype: progressive alopecia, pili torti, widely-spaced peg-shaped teeth, syndactyly fingers 2-3/3-4, toes 2-3/4-5. Study shows that the variants results in exon 4 skipping, leading to a p.(Phe244CysfsX22) change (premature stop codon).
Family B - 2 sibs born to nonconsanguineous Italian parents; phenotype: alopecia, pili torti, abnormal teeth, cutaneous syndactyly. Compound heterozygous c.554C>T (p.Thr185Met) + c.906delT (p.Pro304HisfsX2). 50% reduced mRNA expression in cultured epidermal keratinocytes of patient II:1 (family B).

PMID: 21346770, Jelani et al. 2011
10 affected individuals across a consanguineous Pakistani pedigree. Used microsatellite markers to assign disease locus. Affected individuals homozygous for c.635C>G; p.Pro212Arg - LOD score 5.05. Phenotype: sparse hair, conical teeth with enamel hypoplasia, nail dystrophy, palmoplantar keratoderma, bilateral syndactyly fingers 3-4 and toes 2-3.

PMID: 34067522 Rotunno et al., 2021
Reports 5yo female patient; c.1150delC (p.Gln384ArgfsTer7), homozygous; phenotype: Brittle hair, sparse eyebrows/eyelashes, toenail dystrophy, mild palmoplantar keratoderma. Her teeth were widely spaced and conical, with small crowns and enamel hypoplasia + agenesis of 4 wisdom teeth.

PMID: 37829154 Ali et al., 2023
Consanguineous Kashmiri Family. All 4 affected individuals harboured a homozygous nonsense variant NM 030916: c.181C > T, p.(Gln61Ter). Method: WES. Hypotrichosis, syndactyly fingers 3-4 and toes 2-3, discolored nails, upper lip cleft; conical teeth, with enamel ridges, and pits, widely spaced.

PMID: 37183149 Hajra et al., 2023
Large consanguineous Pakistani family. Only NECTIN4 coding region sequenced. All 15 affected individuals were homozygous for c.163C>T; p.(Arg55*). Phenotype: sparse hair; hypoplastic nails with thick flat discoloured nail plates; peg-shaped, conical, and widely spaced teeth with enamel hypoplasia; proximal cutaneous syndactyly of fingers and toes; skin was dry and scaly with hyperkeratosis and palmoplantar keratoderma.

NECTIN4, previously known as PVRL4, is linked to Ectodermal dysplasia-syndactyly syndrome 1, 613573 (OMIM, accessed 7th Nov 2025).

Created: 7 Nov 2025, 2:33 p.m. | Last Modified: 7 Nov 2025, 2:33 p.m.

Panel Version: 4.13

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ectodermal dysplasia-syndactyly syndrome 1, OMIM:613573; ectodermal dysplasia-syndactyly syndrome 1, MONDO:0024565

Publications

• 20691405
• 21346770
• 34067522
• 37183149
• 37829154

added new-gene-name tag

Created: 9 Dec 2016, 4:24 p.m.

Comment when marking as ready: Associated with phenotype in OMIM and G2P. At least four variants reported

Created: 10 Aug 2016, 10:44 a.m.

Comment on list classification: Expert review green

Created: 10 Aug 2016, 10:42 a.m.

Green List (high evidence)

Ok ED syndactyly

Created: 19 Nov 2015, 3:06 p.m.

Phenotypes
Ectodermal dysplasia syndactyly