脊柱侧凸Ehlers-Danlos综合征(kEDS)是一种罕见的常染色体隐性遗传性结缔组织疾病,其特征是进行性脊柱侧凸,先天性肌张力减退,明显的关节过度活动,和严重的皮肤过度扩张和脆弱性。由于PLOD1(原胶原-赖氨酸,2-酮戊二酸5-双加氧酶1)基因已被确定为kEDS(kEDS-PLOD1)的致病原因。到目前为止,kEDS-PLOD1在中国人群中没有报道。
一名17岁的中国男性患者出现张力减退,关节活动过度和脊柱侧凸被转诊到我们医院。出生后,他被发现患有严重的低张力症,导致运动发育延迟。随后,关节过度活动,发现脊柱侧后凸和弱视。腹股沟疝在5岁时发现,并通过手术闭合。同时,轻微创伤后,他表现出可过度扩张和瘀伤的天鹅绒般的皮肤,萎缩性疤痕扩大。在6岁时注意到肘关节脱位。在10岁时进行了矫正脊柱侧后凸的骨科手术。他的家族史平淡无奇。体格检查显示血压升高。轻微的面部畸形,包括高腭,后背褶皱,并发现了下倾斜的睑裂。他也有蓝色巩膜,听力正常。X线显示严重的脊柱侧凸和骨量减少。超声心动图检查结果正常。实验室检查显示骨转换略有升高。根据我们病人的临床表现,KEDS被怀疑。遗传分析揭示了PLOD1的一种新的纯合错义突变(c.1697G>A,p.C566Y),确认kEDS-PLOD1的诊断。患者接受阿法骨化醇和硝苯地平治疗。12个月随访后,发现体力改善,血压正常。
这是中国血统的kEDS-PLOD1的首例。我们确定了PLOD1的一个新突变,扩展了PLOD1的突变谱。先天性肌张力减退患者应考虑kEDS-PLOD1的诊断,进行性脊柱侧后凸,关节过度活动,和皮肤过度伸展性,并通过PLOD1的突变分析证实。
Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by progressive kyphoscoliosis, congenital muscular hypotonia, marked joint hypermobility, and severe skin hyperextensibility and fragility. Deficiency of lysyl hydroxylase 1 (LH1) due to mutations of PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) gene has been identified as the pathogenic cause of kEDS (kEDS-PLOD1). Up to now, kEDS-PLOD1 has not been reported among Chinese population.
A 17-year-old Chinese male patient presenting with hypotonia, joint hypermobility and scoliosis was referred to our hospital. After birth, he was found to have severe hypotonia leading to delayed motor development. Subsequently, joint hypermobility, kyphoscoliosis and amblyopia were found. Inguinal hernia was found at age 5 years and closed by surgery. At the same time, he presented with hyperextensible and bruisable velvety skin with widened atrophic scarring after minor trauma. Dislocation of elbow joint was noted at age of 6 years. Orthopedic surgery for correction of kyphoscoliosis was performed at age 10 years. His family history was unremarkable. Physical examination revealed elevated blood pressure. Slight facial dysmorphologies including high palate, epicanthal folds, and down-slanting palpebral fissures were found. He also had blue sclerae with normal hearing. X-rays revealed severe degree of scoliosis and osteopenia. The Echocardiography findings were normal. Laboratory examination revealed a slightly elevated bone turnover. Based on the clinical manifestations presented by our patient, kEDS was suspected. Genetic analysis revealed a novel homozygous missense mutation of PLOD1 (c.1697 G > A, p.C566Y), confirming the diagnosis of kEDS-PLOD1. The patient was treated with alfacalcidol and nifedipine. Improved physical strength and normal blood pressure were reported after 12-month follow-up.
This is the first
case of kEDS-PLOD1 of Chinese origin. We identified one novel mutation of PLOD1, extending the mutation spectrum of PLOD1. Diagnosis of kEDS-PLOD1 should be considered in patients with congenital hypotonia, progressive kyphoscoliosis, joint hypermobility, and skin hyperextensibility and confirmed by mutation analysis of PLOD1.