Abcd Syndrome

A number sign (#) is used with this entry because ABCD syndrome can be caused by homozygous mutation in the endothelin B receptor gene (EDNRB; 131244) and is thus allelic to some cases of Waardenburg-Shah syndrome (WS4A; 277580).

Clinical Features

Gross et al. (1995) described a new neural crest syndrome with autosomal recessive inheritance. The proband was a macrosomic newborn girl with albinism, a black lock at the right temporal occipital region, and retinal depigmentation. Bilateral deafness was confirmed by brainstem auditory evoked potentials. In addition, the infant had a severe defect of intestinal innervation. Biopsy showed aganglionosis of the large intestine together with total absence of neurocytes and nerve fibers in the small intestine, indicating a total lack of sympathetic and parasympathetic innervation. The infant died of intestinal dysfunction at 5 weeks. She was the fourteenth child of consanguineous Kurdish parents. Four sibs had died a few days after birth with the same syndrome. The other 9 sibs were healthy, with an unremarkable phenotype.

This disorder has some similarity to the black lock-albinism-deafness syndrome (BADS; 227010) described by Witkop (1979).

Molecular Genetics

Noting the phenotypic overlap between ABCD syndrome and Waardenburg-Shah syndrome, Verheij et al. (2002) screened DNA from the child described by Gross et al. (1995) for mutations in the EDNRB gene and identified a homozygous nonsense mutation (131244.0008). They found that heterozygous family members showed no features of Waardenburg-Shah syndrome.