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

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.

This study reported the characteristics, examination results, diagnosis and treatment of a female case aged 3 years and 3 months.

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.

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.