A familial case of congenital central hypoventilation syndrome due to a combination of polyalanine repeat mutation and novel nonpolyalanine repeat mutation.

Congenital central hypoventilation syndrome is a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation caused by mutations in the paired-like homeobox 2b gene. Among these mutations, the co-occurrence of 2 paired-like homeobox 2b mutations is very rare. Herein, we report a case involving 3 individuals from a 2-generation family, each carrying a heterozygous paired-like homeobox 2b 20/25 polyalanine repeat mutation and a novel nonpolyalanine repeat mutation, c.531C>G, on the same allele with variable phenotypes. Although many patients with 20/25 polyalanine repeat mutation are reported to exhibit normal psychomotor development, 1 individual presented with a significantly more severe psychomotor developmental delay. Determining whether the neurodevelopmental deficits in patients with congenital central hypoventilation syndrome stem from the underlying disease or hypoxic encephalopathy due to insufficient respiratory management is challenging. To understand the potential impact of the novel nonpolyalanine repeat mutation on phenotype, further research is necessary. CITATION: Omata K, Shindo T, Nagao M, Namai Y. A familial case of congenital central hypoventilation syndrome due to a combination of polyalanine repeat mutation and novel nonpolyalanine repeat mutation.