The reference OMIM entry for this protein is 193530

Weyers acrofacial dysostosis; wad
Acrodental dysostosis of weyers
Curry-hall syndrome

A number sign (#) is used with this entry because of evidence that Weyers acrofacial dysostosis (WAD) is caused by heterozygous mutation in the EVC (604831) or the EVC2 (607261) gene. Mutations in the same genes cause Ellis-van Creveld syndrome (225500), an allelic disorder with autosomal recessive inheritance.

DESCRIPTION

Weyers acrofacial dysostosis is an autosomal dominant condition with dental anomalies, nail dystrophy, postaxial polydactyly, and mild short stature. Ellis-van Creveld syndrome is a similar disorder, with autosomal recessive inheritance and the additional features of disproportionate dwarfism, thoracic dysplasia, and congenital heart disease (summary by Howard et al., 1997).

CLINICAL FEATURES

Under the designation acrofacial dysostosis, Weyers (1952) described a syndrome of postaxial polydactyly with anomalies of the lower jaw, dentition and oral vestibule, and proposed autosomal dominant inheritance. Weyers (1956) was aware of similarities to the Ellis-van Creveld syndrome. Roubicek and Spranger (1984) reported an affected 4-generation family. Lower and upper incisors were abnormal in shape and number. Additional findings were prominent ear antihelices, hypoplastic and dysplastic nails, and mild shortness of stature. Inheritance was dominant (no male-to-male transmission was observed) with variable expression. To differentiate it from other acrofacial dysostoses, they suggested naming the condition acrodental dysostosis. Curry and Hall (1979) described a large Spanish-Mexican family in which several members had an autosomal dominant syndrome of postaxial polydactyly, conical teeth, nail dysplasia, and short limbs. Shapiro et al. (1984) reported a similar, isolated case in a 16-year-old male of Cherokee, Irish and German extraction. His father and mother, who were not related, were 32 and 26 years of age, respectively, at his birth. Roubicek and Spranger (1984) concluded that patients reported by Curry and Hall (1979) and Shapiro et al. (1984) had Weyers acrofacial dysostosis. Turnpenny (1995) examined a family with features that suggested some overlap between this disorder and Pallister-Hall syndrome (PHS; 146510). This family had a mother and son affected with fourth finger duplication and nail and dental dysplasia. The mother had gelastic epilepsy (a form characterized by laughter) and the son had imperforate anus. The absence of MRI findings of hypothalamic hamartomas in these patients argued against Pallister-Hall syndrome but gelastic epilepsy has been associated with hypothalamic lesions, suggesting a functional if not anatomic lesion of this area.

MAPPING

Howard et al. (1997) studied a 4-generation family with features of Weyers acrofacial dysostosis in which the proband had a more severe phenotype resembling Ellis-van Creveld syndrome. By linkage and haplotype analysis, Howard et al. (1997) determined that the disease locus in this pedigree resided on 4p16 in a region that includes the EVC locus. The authors concluded that the genes for the condition in the family of Howard et al. (1997) and for EVC are near one another or that these 2 conditions are allelic. The data also raised the possibility that Weyers acrofacial dysostosis is a heterozygous expression of the mutation that, in homozygous form, causes the autosomal recessive disorder EVC.

MOLECULAR GENETICS

Ruiz-Perez et al. (2000) determined that a child with EVC, whose father had Weyers acrodental dysostosis ( ... More on the omim web site

Subscribe to this protein entry history

Feb. 23, 2019: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 193530 was added.