Asphyxiating thoracic dystrophy associated with IFT74 pathogenic variant: a case report

Abstract

Asphyxiating Thoracic Dystrophy (ATD) is a rare skeletal ciliopathy characterized by a constricted thoracic cage, short ribs, and pulmonary hypoplasia. While typically linked to pathogenic variants in IFT80 or DYNC2H1 , recent genomic advancements have identified biallelic variants in IFT74 as a cause of short-rib thoracic dysplasia type 20 ( SRTD20 ). Due to its rarity, the clinical progression and phenotypic spectrum of IFT74-related ATD remain poorly understood. We report the case of a term male infant presenting at birth with severe respiratory distress, macrocephaly, and a narrow chest with pectus excavatum. Initial radiographic skeletal surveys were inconclusive for classic dysplasia. Despite intensive neonatal care, the patient experienced persistent respiratory failure, recurrent atelectasis, and profound axial hypotonia. Magnetic resonance imaging (MRI) revealed no structural abnormalities. Whole exome sequencing (WES) identified a homozygous pathogenic copy number loss in the IFT74 gene. The clinical course was complicated by severe oropharyngeal dysphagia and recurrent aspiration pneumonia. Despite gastrostomy placement and maximal supportive care, the infant suffered a fatal cardiopulmonary arrest at four months of age. This case highlights a lethal neonatal phenotype of IFT74-related SRTD2 0, reinforcing the critical role of IFT74 in ciliary assembly and axonal guidance. Early WES is essential for diagnosing genetically heterogeneous skeletal dysplasias, providing accurate prognostic counseling, and guiding end-of-life discussions in cases of severe thoracic insufficiency.