Hereditary sensory and autonomic neuropathies (HSAN) encompass a group of peripheral nervous system disorders characterized by remarkable heterogeneity from a clinical and genetic point of view. Mutations in SPTLC1 gene are responsible for HSAN type IA, which usually starts from the second to fourth decade with axonal neuropathy, sensory loss, painless distal ulcerations, and mild autonomic features, while motor involvement usually occur later as disease progresses. Beyond the classic presentation of HSAN type IA, an exceedingly rare distinct phenotype related to SPTLC1 mutations at residue serine 331 (S331) has recently been reported, characterized by earlier onset, prominent muscular atrophy, growth retardation, oculo‐skeletal abnormalities, and possible respiratory complications. In this report, we describe clinical, instrumental, and genetic aspects of a 13‐year‐old Sri Lankan male carrying the rare de novo p.S331Y heterozygous mutation in SPTLC1 gene found by whole exome sequencing. Patient's phenotype partly overlaps with the first case previously reported, however with some additional features not described before. This work represent the second report about this rare mutation and our findings strongly reinforce the hypothesis of a clearly distinct “S331 syndrome”, thus expanding the spectrum of SPTLC1‐related disorders.

中文翻译：

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将 SPTLC1 相关疾病的范围扩大到遗传性感觉和自主神经病变之外：一个独特的“S331 综合征”的新病例。

遗传性感觉和自主神经病 (HSAN) 包括一组周围神经系统疾病，其特征是从临床和遗传的角度来看具有显着的异质性。SPTLC1基因突变是导致 HSAN IA 型的原因，通常从 20 岁到 40 岁开始出现轴突神经病变、感觉丧失、无痛性远端溃疡和轻度自主神经特征，而随着疾病的进展，运动受累通常发生得更晚。除了 HSAN IA 型的经典表现之外，还有一种与SPTLC1相关的极其罕见的独特表型最近报道了残基丝氨酸 331 (S331) 的突变，其特征是发病早、肌肉萎缩明显、生长迟缓、眼骨骼异常和可能的呼吸系统并发症。在本报告中，我们描述了一名 13 岁斯里兰卡男性的临床、仪器和遗传方面，该男性携带通过全外显子组测序发现的SPTLC1基因中罕见的 de novo p.S331Y 杂合突变。患者的表型与先前报告的第一个病例部分重叠，但有一些之前未描述的其他特征。这项工作代表了关于这种罕见突变的第二份报告，我们的发现有力地强化了明显不同的“S331 综合征”的假设，从而扩大了SPTLC1相关疾病的范围。