The first report of a gross deletion in the SCNN1G gene in a case presenting with hyponatremic convulsion at fifth year of treatment.

OBJECTIVES

Systemic pseudohypoaldosteronism type 1(PHA1) is a rare, autosomal recessive disorder resulting from loss-of-function mutations in epithelial sodium channel subunit genes. These mutations lead to aldosterone resistance in multiple tissues and typically manifest as hyponatremia, hyperkalemia, and metabolic acidosis.

CASE PRESENTATION: We report the case of a male infant with a history of severe neonatal hyponatremia and hyperkalemia. The case presented to our center with persistent electrolyte imbalances and treatment-resistant eczematous skin lesions. Initial sequencing of PHA1-associated genes (SCNN1A, SCNN1B, and SCNN1G) did not reveal any pathogenic variants. At the age of five, the case experienced a febrile seizure, during which laboratory related biochemical tests showed isolated hyponatremia with normokalemia. Further genetic work-up with high-resolution chromosomal microarray analysis was performed, revealing a novel homozygous gross deletion involving exons 2-3 of the SCNN1G gene.

CONCLUSIONS

This is the first reported case of a homozygous gross deletion in the SCNN1G gene. This case expands the phenotypic and genotypic spectrum of systemic PHA1 and emphasizes the importance of considering copy number variants in genetically unresolved cases of PHA1, especially those presenting with atypical electrolyte profiles and extrarenal manifestations such as persistent eczema.