A twin with a novel pathogenic variant in CYBB induced X-linked chronic granulomatous disease: a rare case report of misdiagnosis as congenital cystic lung disease

TL;DR

A twin with a new CYBB gene mutation was misdiagnosed with lung disease but actually had a rare immune disorder called X-linked chronic granulomatous disease.

Contribution

A novel CYBB pathogenic variant (c.1303A > T, p.Lys435Ter) is identified in a case of X-linked chronic granulomatous disease.

Findings

The proband had a novel CYBB mutation and recurrent infections misdiagnosed as congenital cystic lung disease.

The twin brother shared the same mutation but remained asymptomatic, showing phenotypic discordance.

Neutrophil function testing confirmed impaired respiratory burst activity consistent with CGD.

Abstract

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by defects in phagocyte NADPH oxidase. X-linked CGD, resulting from CYBB gene mutations, accounts for approximately two-thirds of cases. Clinical manifestations typically include recurrent bacterial and fungal infections, granuloma formation, and inflammatory complications.

We report monochorionic diamniotic twins with a novel CYBB variant (c.1303A > T, p.Lys435Ter). The 7-month-old proband presented with recurrent respiratory infections and was initially misdiagnosed with congenital cystic lung disease. His twin brother carried the identical mutation but remained asymptomatic. Neutrophil function testing demonstrated impaired respiratory burst activity. Whole-exome sequencing confirmed a de novo nonsense mutation in the CYBB gene.

This case highlights the diagnostic challenges of CGD and illustrates remarkable phenotypic discordance in monochorionic twins with identical genetic mutations. Environmental factors and epigenetic modifications may contribute to variable expressivity. Early genetic testing is crucial for accurate diagnosis and appropriate management of suspected primary immunodeficiency disorders.

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