Case report: Dominant deafness-onychodystrophy syndrome and hypokalemic periodic paralysis in a single patient: a rare syndromic overlap

Dong-Lan Luo¹Rui Ping Liu²Xin-yi Hou^2,3Zhi Liu⁴Bin Lu^2,3*

• ¹Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, China
• ²Jining Medical University, Jining, China
• ³Affiliated Hospital of Jining Medical University, Jining, China
• ⁴The Affiliated Hospital of Guizhou Medical University, Guiyang, China

Dominant deafness-onychodystrophy syndrome (DDOD) and hypokalemic periodic paralysis (HypoPP) are distinct autosomal dominant disorders caused by mutations in ATP6V1B2 and CACNA1S, respectively. We describe an eight-year-old female with congenital deafness, nail dysplasia, enamel hypoplasia, and recurrent episodes of hypokalemia-induced muscle weakness. Whole-exome sequencing (WES) revealed a de novo ATP6V1B2 nonsense variant (c.1516C>T, p.Arg506Ter) and a maternally inherited CACNA1S missense variant (c.1583G>A, p.Arg528His). The proband 's mother and maternal grandfather carried the same CACNA1S variant with milder periodic weakness, indicating intrafamilial variability and reduced penetrance. This dual diagnosis broadens the phenotypic spectrum of both DDOD and HypoPP and illustrates how comprehensive genomic testing can elucidate complex, blended phenotypes. Although no direct mechanistic link between ATP6V1B2 and CACNA1S has been demonstrated, their coexistence highlights the importance of considering multilocus genetic etiologies in rare diseases and supports precision medicine approaches integrating genomic diagnostics and individualized management.