CHOPS Syndrome: A Rare Malformation Syndrome with de novo AFF4 Gene Variant

CHOPS syndrome is a rare, multisystem disorder caused by heterozygous pathogenic variants in the AFF4 gene. The acronym CHOPS is characterized by Cognitive impairment and coarse facial features (C), Heart defects (H), Obesity (O), Pulmonary involvement (P), and Short stature/skeletal dysplasia (S). The syndrome is caused by variants in AFF4, which encodes a protein critical for RNA polymerase II elongation and transcriptional regulation.

A 6-year-old male patient with CHOPS syndrome was diagnosed with a heterozygous de novo c.764C>T (p.Ala255Val) variant in AFF4. The patient exhibited significant growth failure despite an adequate growth hormone response. Also, the patient presented with impairment, dysmorphic features, and neuroimaging findings indicative of cortical atrophy and corpus callosum hypoplasia. Additional features included congenital cataracts, laryngomalacia, and mild mitral insufficiency.

This case report of CHOPS syndrome, caused by a de novo AFF4 variant, highlights the multifactorial nature of growth and neurodevelopmental disturbances. Early genetic diagnosis and a multidisciplinary approach are essential for optimal patient care.