A novel homozygous mutation in PVRL4 causes ectodermal dysplasia‐syndactyly syndrome 1

Abstract

Ectodermal dysplasias (EDs) are a group of hereditary disorders defined by alterations in two or more ectodermal structures. One recently described rare entity is the autosomal recessive inherited ectodermal dysplasia-syndactyly syndrome 1 (EDSS1). Homozygous and compound heterozygous missense and nonsense mutations in the poliovirus receptor related-4 (PVRL4) gene, encoding cell adhesion molecule nectin-4, have been identified as causal for EDSS1. We here report a consanguineous family with a 2-year-old girl featuring EDSS1, including slowly progressive alopecia on the head, pili torti-like twisted hairs in trichoscopy, widely spaced, peg-shaped and conical teeth, proximal syndactyly with fusion of the 2nd to 4th toes, and generalized dry skin. There was no palmoplantar hyperkeratosis and sweating appeared normal to slightly enhanced, especially on the head. Using exome sequencing, we identified the novel homozygous nonsense mutation c.229C>T (p.Gln77Ter) in PVRL4.

Ectodermal Dysplasia-Syndactyly Syndrome with Toe-Only Minimal Syndactyly Due to a Novel Mutation in NECTIN4: A Case Report and Literature Review

“…Her clinical presentation was unique in that she presented with minimal cutaneous syndactyly. A literature review identified three sporadic EDSS1 cases and six families with two or more affected members ( Table 1 ) [ 4 , 6 , 14 , 16 , 17 , 18 , 19 , 20 ]. The patients originated from Denmark, Turkey, Algeria, Italy, Afghanistan, Pakistan, Azad Jammu and Kashmir.…”

“…The patients originated from Denmark, Turkey, Algeria, Italy, Afghanistan, Pakistan, Azad Jammu and Kashmir. Consanguinity was reported in seven families [ 4 , 6 , 14 , 17 , 18 , 19 , 20 ]. A proximal bilateral cutaneous syndactyly of both fingers and toes was present in previous cases [ 4 , 14 , 17 , 18 , 19 , 20 ], with the exception of a girl who had involvement limited to toes [ 6 ].…”

“…Our patient had mild scalp hypotrichosis with fragile hair and sparse eyelashes and eyebrows. Hypotrichosis is a constant and early finding in EDSS1; it has a progressive course, which can lead to alopecia in adulthood [ 4 , 6 , 14 , 16 , 17 , 19 , 20 ]. In addition, a family with congenital alopecia has been described [ 18 ].…”

“…Few NECTIN4 mutations have thus far been described in EDSS1 and no genotype-phenotype correlations have yet been reported. However, three clinical features (cutaneous syndactyly and abnormalities of the hair and teeth) are reported as constant in EDSS1 despite the different NECTIN4 causative mutations [ 4 , 5 , 6 ]. Here, we report on a 5.5-year-old girl who is suspected of being affected by ED based on the presence of hair and tooth abnormalities and toe-nail dystrophy.…”

Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use

“…NECTIN4 is highly expressed in the skin (https://www.ncbi.nlm.nih.gov/gene/81607/?report=expression). Mutations in NECTIN4 may cause ectodermal dysplasia-syndactyly syndrome (EDSS1), which is an autosomal disorder [17][18][19]. In our previous study, we found that plasma cadherin 2 (CDH2) was associated with methadone dose change [20].…”