Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disease resulting from mutations in the NTRK1 gene encoding the neurotrophic tyrosine kinase-1 receptor. In this multicenter observational retrospective study, we investigated CIPA patients identified from French laboratories sequencing the NTRK1 gene, and seven patients were identified. Patients originated from France (2), Suriname (2), Mali (1), Kazakhstan (1), and Algeria (1). Mean age of patients was 9.8 years (4–20), four patients were female (57%), infant developmental milestones were delayed in four cases (57%), and four patients had a family history of consanguinity (57%). Mean age at diagnosis was 4.8 months (3–6), and all patients presented with pain insensitivity, anhidrosis, intellectual disability, self-mutilation, febrile episodes, impaired temperature perception, and autonomous nervous system impairment. Patients also showed an assortment of associated findings, including hyperactivity (86%), emotional lability (86%), joint deformities (71%), bone fractures (57%), abnormal sense of touch, vibration and position (50%), skin, hair and nails abnormalities (28%), and hypothermia episodes (28%). Two patients died at age 9 and 12 years from infection. In three cases, nerve conduction studies showed absent lower limbs sensory nerve action potentials. In one case, sensory nerve biopsy showed complete absence of unmyelinated fibers. Nine NTRK1 pathogenic variants were found, including three newly described mutations. This nationwide study confirms that NTRK1 gene-related CIPA is an extremely rare disorder and expands the genotypic spectrum of NTRK1 mutations.

先天性疼痛不敏感伴无汗症 (CIPA) 是一种罕见的常染色体隐性遗传病，由编码神经营养性酪氨酸激酶-1 受体的NTRK1基因突变引起。在这项多中心观察性回顾性研究中，我们调查了从法国实验室确定的对NTRK1进行测序的 CIPA 患者基因，并确定了七名患者。患者来自法国 (2)、苏里南 (2)、马里 (1)、哈萨克斯坦 (1) 和阿尔及利亚 (1)。患者的平均年龄为 9.8 岁（4-20 岁），4 名患者为女性（57%），4 名患者的婴儿发育里程碑延迟（57%），4 名患者有血缘家族史（57%）。诊断时的平均年龄为 4.8 个月（3-6 个月），所有患者均出现疼痛不敏感、无汗、智力障碍、自残、发热、温度感知受损和自主神经系统障碍。患者还表现出各种相关的发现，包括多动（86%）、情绪不稳定（86%）、关节畸形（71%）、骨折（57%）、触觉、振动和位置异常（50%），皮肤、头发和指甲异常（28%），和体温过低事件（28%）。两名患者在 9 岁和 12 岁时死于感染。在三个病例中，神经传导研究显示下肢感觉神经动作电位缺失。在一个病例中，感觉神经活检显示完全没有无髓纤维。九发现了NTRK1致病变异，包括三个新描述的突变。这项全国性研究证实NTRK1基因相关的 CIPA 是一种极为罕见的疾病，并扩大了NTRK1突变的基因型谱。