Minde Jan, Svensson Olle, Holmberg Monica, Solders Göran, Toolanen Göran
Department of Orthopedics, Gällivare Hospital, Gällivare,
Acta Orthop. 2006 Apr;77(2):198-202. doi: 10.1080/17453670610045911.
Congenital insensitivity to pain is a rare hereditary sensory neuropathy.
We present 6 patients from a family with a mutation in the nerve growth factor beta gene (NGFB).
3 patients were homozygous with a mutilating arthropathy starting early in life, and 3 patients were presumably heterozygous with a milder course starting in adulthood. All patients had normal mental abilities. In addition to absence of deep pain, the patients had impaired temperature sensation, but no autonomic deficiency. Sural nerve biopsies showed a moderate loss of A-delta fibres and a severe reduction in C fibers. Clinically, the disorder most often affected the lower extremities, with an insidious progressive joint swelling or a painless fracture, but the spine could also be involved with gross and unstable spondylolisthesis. Fracture healing was uneventful, but the arthropathy was progressive, eventually resulting in gross deformity and instability. When treating patients with congenital disorders such as this one, it is important to consider the slowly progressive nature of the disorder, and the orthopedic operations should therefore be planned from a long-term standpoint. Arthrodesis, limb lengthening and spinal decompression or fusion are the only elective procedures that seem reasonable. Fitting of orthosis for joint protection is also demanding. To delay the development of neuropathic arthropathy, patient education is essential but difficult in the very young.
The different expression between homo- and heterozygous subjects and the central role of nerve growth factor make this disease an interesting model system for studies of disease mechanisms and the molecular background to pain.
先天性无痛觉是一种罕见的遗传性感觉神经病。
我们报告了来自一个神经生长因子β基因（NGFB）发生突变的家族的6名患者。
3名患者为纯合子，自幼起就患有致残性关节病，3名患者可能为杂合子，成年后病情较轻。所有患者智力正常。除了深部痛觉缺失外，患者还存在温度觉受损，但无自主神经功能障碍。腓肠神经活检显示A-δ纤维中度缺失，C纤维严重减少。临床上，该疾病最常累及下肢，表现为隐匿性进行性关节肿胀或无痛性骨折，但脊柱也可能受累，出现严重且不稳定的椎体滑脱。骨折愈合过程顺利，但关节病呈进行性发展，最终导致严重畸形和不稳定。在治疗此类先天性疾病患者时，重要的是要考虑到疾病进展缓慢的特点，因此骨科手术应从长期角度进行规划。关节固定术、肢体延长术以及脊柱减压或融合术是唯一看似合理的选择性手术。为保护关节而佩戴矫形器也颇具挑战性。为延缓神经性关节病的发展，患者教育至关重要，但对于年幼患者来说却很困难。
纯合子和杂合子个体之间的不同表现以及神经生长因子的核心作用，使这种疾病成为研究疾病机制和疼痛分子背景的一个有趣的模型系统。
