Department of Pediatrics, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Mol Genet Genomic Med. 2022 Nov;10(11):e2039. doi: 10.1002/mgg3.2039. Epub 2022 Sep 2.
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.
EVEN-plus 综合征（骨骺-椎体-耳-鼻发育不良伴相关表现）是一种极其罕见的常染色体隐性遗传性疾病，其特征为特定的面部特征和骨骼发育不良。由于 HSPA9 基因的缺陷，该疾病具有产前发病的特点。该综合征此前在中国尚未有报道。
本研究报道了一名 3 岁零 3 个月女性患者的特征、检查结果、诊断和治疗情况。
患者存在全面发育迟缓以及特定的面部特征，包括额骨突出、双侧耳廓畸形、塌鼻、高腭弓、短颈和其他外观异常。其髋关节磁共振成像（MRI）结果显示双侧股骨头骨骺发育不良，末端呈叉状畸形，脑部 MRI 显示白质髓鞘发育不良。外显子组测序鉴定出 HSPA9 复合杂合变异 c.882_c.883delAG 和 c.613A>G。
该发现扩展了 EVEN-plus 综合征表型和致病变异的谱，提示 c.882_c.883delAG 在东亚人群中的分布频率可能较高。
