Zhang Xianzuo, Liang Haiyi, Liu Weilu, Li Xu, Zhang Wenzhi, Shang Xifu
Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001 China.
CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, Hefei, Anhui 230026, China.
Medicine (Baltimore). 2019 Jul;98(30):e16485. doi: 10.1097/MD.0000000000016485.
Spondylometaphyseal dysplasia (SMD) is an extremely rare disorder of irregular development of spine and metaphyses of long tubular bones. Mutations in the collagen type X alpha 1 gene were found to underlie this condition. Previously reported mutations in the N-terminal non-collagenous NC2 domain and C-terminal non-collagenous NC1 domain failed to be identified in some specific patients.
A 23-year-old male was referred to us for fixed, angular thoracolumbar kyphosis with semi-paralysis, numbness, and tremor on his left lower limb. Marked hypoplasia of thoracolumbar vertebra and spinal canal stenosis were observed on radiology.
He was diagnosed with spondylometaphyseal dysplasia (Type A4). Gene sequencing was performed using normalized targeted regions sequencing (TRS). A novel heterozygous missense variant p.Gly139Cys in the triple-helical region. Multiple lines of evidence imply this mutation to be pathogenic.
Posterior instrumentation and vertebral column resection were given to correct his fixed, angular thoracolumbar kyphosis.
The correction was satisfying and the functional outcomes were good.
The findings corroborated that type X collagen plays a critical role in the formation of the human spine as well as the long bones, and further expanded the range of type X collagenopathy. Surgical procedure could be considered for patients with severe malformation and neurological impairments.
脊椎干骺端发育异常（SMD）是一种极为罕见的疾病，表现为脊柱和长管状骨干骺端的不规则发育。研究发现，X型胶原α1基因的突变是导致这种疾病的原因。先前报道的N端非胶原NC2结构域和C端非胶原NC1结构域的突变，在一些特定患者中未被发现。
一名23岁男性因固定性胸腰椎角状后凸畸形伴左下肢半瘫痪、麻木和震颤前来就诊。影像学检查发现胸腰椎明显发育不全和椎管狭窄。
他被诊断为脊椎干骺端发育异常（A4型）。采用标准化靶向区域测序（TRS）进行基因测序。在三螺旋区域发现了一个新的杂合错义变体p.Gly139Cys。多项证据表明该突变具有致病性。
进行后路内固定和脊柱切除术以纠正其固定性胸腰椎角状后凸畸形。
矫正效果满意，功能结果良好。
研究结果证实X型胶原在人类脊柱和长骨的形成中起关键作用，并进一步扩大了X型胶原病的范围。对于严重畸形和神经功能障碍的患者可考虑手术治疗。
