Work

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

Year: 2026

Type: article

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.

Source: Frontiers in Pediatrics

DOI: 10.3389/fped.2025.1674481

Authors: Dong-Lan Luo, Rui-Ping Liu, Xin-Yi Hou, Zhi Liu, Bin Lu

Institutions: Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Jining Medical University, Affiliated Hospital of Jining Medical University, Affiliated Hospital of Guizhou Medical University

Language: English

Topic: Genomics and Rare Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801