Congenital Heart Defects And Ectodermal Dysplasia

A number sign (#) is used with this entry because of evidence that congenital heart defects and ectodermal dysplasia (CHDED) is caused by heterozygous mutation in the PRKD1 gene (605435) on chromosome 14q12.

Clinical Features

Sifrim et al. (2016) reported 3 unrelated children with a syndrome associated with congenital heart defects. Two patients had atrioventricular septal defects and the third had pulmonary valve abnormality. All had some sort of developmental delay, with global developmental delay and motor delay noted in 1 patient, and delayed speech and language in another. Developmental details about the third patient were not provided. Two patients were noted to have variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third patient had a 'disorganized eyebrow.' Other features seen in 1 or 2 patients included microcephaly, prominent forehead, prominent nasal bridge, depressed nasal bridge, broad thumbs, short digits, nystagmus, scoliosis, feeding difficulties, and hypotonia.

Molecular Genetics

In 3 unrelated children with CHDED, Sifrim et al. (2016) identified de novo heterozygous missense mutations in the PRKD1 gene (605435.0002-605435.0003). The patients were ascertained from a cohort of 518 trios in which a child with syndromic congenital heart defects underwent exome sequencing. Statistical analysis indicated that de novo missense mutations in the PRKD1 gene were significantly enriched in patients compared to those expected under a null mutational model (p = 2.13 x 10(-6), Bonferroni-corrected p = 0.05). Functional studies of the variants and studies of patient cells were not performed.