Coexistence of congenital central hypoventilation syndrome, Hirschsprung disease, and Becker muscular dystrophy

Abstract

Background

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder mostly caused by a genetic defect in PHOX2B. We describe for the first time a case of a male patient with the coexistence of CCHS, Hirschsprung disease (HSCR), and Becker muscular dystrophy (BMD).

Case presentation

The patient presented with hypoventilation and required ventilatory support during the neonatal period. The diagnosis of CCHS was suspected and confirmed by molecular analysis of the PHOX2B gene, revealing a de novo heterozygous polyalanine repeat-expansion mutation containing 27 repeats (normal gene contains 20 repeats). The patient had tracheostomy at 1 month. He also developed abdominal distention. Contrast enema confirmed the diagnosis of HSCR. Transanal decompression tube was indwelled at 2 months and definitive repair was performed at 14 months. During follow-up, he was found to have elevated creatine kinase levels. The dystrophin gene was screened for deletions by Multiplex ligation-dependent probe amplification (MLPA) and the deletion of exons 45–55 of the DMD gene was detected, leading to the diagnosis of BMD. At 7 years of age, he remains on continuous ventilatory support during sleep. He has difficulty playing sports and myalgia, which could be the symptoms due to BMD. So far, he has not exhibited cardiac abnormalities; his Full-Scale Intelligence Quotient score is within the normal range.

Discussion/Conclusion

This case illustrates the importance of recognizing the coexistence of two different monogenic disorders in a single patient and the necessity of appropriate management in patients with CCHS, HSCR, and BMD.