# The First Korean Case with Cardiac, Facial, and Digital Anomalies with Developmental Delay Caused by De Novo TRAF7 p.Arg655Gln Variant

## TL;DR

A 36-year-old man with a rare TRAF7 gene variant showed heart, facial, and developmental issues, with his breathing problems linked to sleep apnea.

## Contribution

Reports the first Korean case of TRAF7 p.Arg655Gln variant causing CAFDADD syndrome with detailed clinical and genetic findings.

## Key findings

- A de novo TRAF7 p.Arg655Gln variant was identified in a patient with CAFDADD syndrome.
- The patient's dyspnea was attributed to obstructive sleep apnea exacerbated by vertebral anomalies.
- Aortic root replacement did not resolve symptoms, but CPAP therapy improved breathing.

## Abstract

TRAF7-related disorders represent some of the rarest inherited disorders, exhibiting clinical features that overlap with cardiac, facial, and digital anomalies with developmental delay (CAFDADD) syndrome, as well as blepharophimosis-mental retardation syndrome (BMRS). A 36-year-old male, presenting with total blindness, blepharophimosis, and intellectual disability, was admitted for the assessment of resting dyspnea several months previously. He had a history of being diagnosed with obstructive sleep apnea (OSA). Transesophageal and transthoracic echocardiography unveiled right ventricular dilatation without significant pulmonary hypertension, bicuspid aortic valve with aortic root aneurysm, and aortic regurgitation in the proband. Sanger sequencing identified a de novo TRAF7 variant (c.1964G>A; p.Arg655Gln). Subsequently, aortic root replacement using the Bentall procedure was performed. However, despite the surgery, he continued to experience dyspnea. Upon re-evaluating OSA with polysomnography, it was discovered that continuous positive airway pressure support alleviated his symptoms. The underlying cause of his symptoms was attributed to OSA, likely exacerbated by the vertebral anomaly and short neck associated with CAFDADD syndrome. Clinicians should be attentive to the symptoms associated with OSA as it is a potentially serious medical condition in patients with TRAF7 variants.