A case of CHOPS syndrome accompanied with moyamoya disease and systemic vasculopathy

CHOPS syndrome, caused by a mutation in the AFF4 gene, is a recently established and extremely rare genetic disorder, which has moderate phenotypic overlap with Cornelia de Lange syndrome. The main phenotypes include characteristic facial features, short stature, obesity, skeletal and pulmonary involvement, and neurodevelopmental impairment.

We report on a Korean girl with CHOPS syndrome presenting with an atypical manifestation. The patient was referred to the out-patient clinic to evaluate the underlying etiology of short stature, obesity, developmental delay, and Moyamoya disease. The patient showed characteristic facial features including a round face, thick eyebrows, and synophrys. Her developmental milestones had been delayed since infancy and a moderate degree of intellectual disability persisted. She was also diagnosed with Moyamoya disease at 6 years of age and had undergone synangiosis surgery thrice. Her renal arteries and infrarenal aorta were diffusely narrowed. A novel de novo missense variant, c.758C > T (p.Pro253Leu) in AFF4 was identified by whole exome sequencing. No additional candidate variants for her vascular manifestation were found except a susceptibility variant, c.14429G > A (p.Arg4810Lys) in RNF213, inherited from asymptomatic mother.

This is the first case of CHOPS syndrome accompanied by systemic vasculopathy. More clinical observations and functional studies are required to clarify this association.