Identifying patients with EVEN‐plus syndrome using exome sequencing and clinical feature analysis: A case report

Abstract

Abstract Background The EVEN‐plus syndrome (epiphyseal–vertebral–ear–nose dysplasia plus associated findings) is an extremely rare autosomal recessive inherited disease characterised by specific facial features and skeletal dysplasia. It has a prenatal onset due to defects in the HSPA9 gene. The syndrome has not been reported previously in China. Methods This study reported the characteristics, examination results, diagnosis and treatment of a female case aged 3 years and 3 months. Results The patient had global developmental delay and specific facial features, including a prominent forehead, a bilateral auricle deformity, a collapsed nose, a high palatine arch, a short neck and other appearance abnormalities. Her hip joint magnetic resonance imaging (MRI) results showed bilateral femoral head epiphyseal dysplasia with a fork‐shaped malformation at the distal end, and her brain MRI showed white matter myelin dysplasia. HSPA9 compound heterozygous variants c.882_c.883delAG and c.613A>G were identified by exome sequencing. Conclusions This finding expands the spectra of EVEN‐plus syndrome phenotype and pathogenic variants and suggests that c.882_c.883delAG may have a higher distribution frequency in East Asian populations.

Keywords

• epiphyseal dysplasia
• EVEN‐plus syndrome
• HSPA9
• microtia