EDNRB – ABCD Syndrome

ABCD syndrome is an autosomal recessive neurocristopathy characterized by albinism, black lock, Hirschsprung disease, and sensorineural deafness. Screening of the index patient revealed a homozygous nonsense variant, c.601C>T (p.Arg201Ter), in the EDNRB gene, resulting in premature truncation of the endothelin-B receptor and loss of neural crest cell migration function (PMID:11891690). This single report supports a causative role for biallelic EDNRB truncating alleles in ABCD syndrome, with clinical features overlapping Shah-Waardenburg syndrome. No additional affected relatives were reported, and functional characterization in this context is lacking. However, EDNRB loss-of-function is well established in related enteric and pigmentary disorders, consistent with a haploinsufficiency mechanism. Further case series and segregation analyses are required to confirm reproducibility and refine genotype–phenotype correlations.

Key Take-home: Biallelic truncating EDNRB variants, such as c.601C>T (p.Arg201Ter), should be considered in patients presenting with the ABCD syndrome triad of pigmentary anomalies, Hirschsprung disease, and deafness, enabling targeted genetic testing and counseling.

References

• American journal of medical genetics • 2002 • ABCD syndrome is caused by a homozygous mutation in the EDNRB gene. PMID:11891690

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