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

## TL;DR

A child with two rare genetic disorders, deafness-onychodystrophy syndrome and hypokalemic periodic paralysis, is reported, showing how genomic testing can reveal complex conditions.

## Contribution

This case report presents a rare overlap of two autosomal dominant disorders with a novel dual genetic diagnosis.

## Key findings

- The patient had a de novo ATP6V1B2 variant and a maternally inherited CACNA1S variant.
- The CACNA1S variant showed intrafamilial variability and reduced penetrance in the family.
- The case highlights the importance of genomic testing in diagnosing complex, blended phenotypes.

## Abstract

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.