# Novel Co‐Occurrence of Trisomy 21 and Heterozygous CFTR Mutation

## TL;DR

A rare case of a child with Down syndrome and a heterozygous CFTR mutation is reported, showing severe respiratory issues.

## Contribution

The paper reports the first known case of trisomy 21 with a heterozygous CFTR mutation, highlighting potential clinical implications.

## Key findings

- A male infant with trisomy 21 had a heterozygous pathogenic CFTR mutation (p.Phe508del) and severe respiratory complications.
- The case suggests that trisomy 21 and CFTR-related airway abnormalities may interact to worsen respiratory outcomes.
- Clinicians should consider CFTR-related disorders in trisomy 21 patients with severe respiratory symptoms.

## Abstract

The coexistence of trisomy 21 and cystic fibrosis (CF) is extremely rare, with fewer than 10 reported cases, all involving homozygous CFTR mutations. However, the impact of a heterozygous CFTR mutation in a patient with trisomy 21 remains unexplored. We present a male infant with trisomy 21 who experienced recurrent respiratory distress and was later found to carry a heterozygous pathogenic CFTR mutation (p.Phe508del). His respiratory complications were severe, requiring tracheostomy and long‐term respiratory support. This case highlights the potential interplay between trisomy 21‐associated anatomical features and CFTR‐related airway abnormalities, possibly exacerbating respiratory morbidity. Given the high burden of respiratory complications in both conditions, clinicians should consider CFTR‐related disorders in patients with trisomy 21 presenting with severe respiratory issues. Further research is warranted to determine the clinical significance of CFTR heterozygosity in trisomy 21 and its implications for disease severity and management.

This article reports a novel co‐occurrence of trisomy 21 and a heterozygous CFTR mutation in an infant.