IllnessNeuropathy, hereditary sensory; differential diagnosis

NGS +

[Sanger]

Hereditary sensory neuropathy type (HSN) IA is a disorder with nerve abnormalities in the legs and feet. Many of the patients suffer from paraesthesias, numbness and a decreased ability to feel pain and sense heat and cold. Some affected individuals do not have sensory disturbances but do experience stabbing pain in the legs and feet. As the disease progresses, sensory disturbances may affect the shoulders, joints and abdomen. As sufferers age, they may also experience muscle atrophy and weakness. People with HSNIA typically develop ulcers on the feet/hands or infections/whitlows, some also show sensorineural hearing loss. HSNIA symptoms can begin at any time during adolescence. Although the features of this disease worsen over time, affected individuals have a normal life expectancy. HSNIA is caused by mutations in the SPTLC1 gene and is inherited in an autosomal dominant manner. Other dominant HSN1 disorders with similar symptoms are caused by pathogenic variants in the SPTLC2, ATL1 and DNMT1 genes. CMT2 disorders with related phenotypes include CMT2B, which is caused by pathogenic variants in RAB7. In CMT2I/J, a specific pathogenic MPZ variant is associated with a phenotype almost identical to HSAN1A. The molecular genetic yield in HSN is currently unknown. Therefore, a negative DNA test result does not refute the clinical neurological diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1390/

• Alias: Hereditary sensory + autonomic (SPTLC1)
• Alias: Neuropathy, hereditary sensory + autonomic
• Alias: Neuropathy, hereditary sensory, HSN1, HSN2
• Alias: Polyneuropathie
• Allelic: Cerebellar ataxia, deafness, narcolepsy, AD (DNMT1)
• Allelic: NESCAV syndrome (KIF1A)
• Allelic: Spastic paraplegia 30, AD + AR (KIF1A)
• Allelic: Spastic paraplegia 3A, AD (ATL1)
• Axonal, non-demyelinating CMT2B: severe sensory loss (RAB7)
• Axonal, non-demyelinating CMT2I/J: severe sensory loss (MPZ)
• Neuropathy, hereditary sensory + autonomic, type IC (RAB7A)
• Neuropathy, hereditary sensory [+ autonomic], type IA (SPTLC1)
• Neuropathy, hereditary sensory, type ID (ATL1)
• Neuropathy, hereditary sensory, type IE (DNMT1)
• Neuropathy, hereditary sensory, type IF (ATL3)
• Neuropathy, hereditary sensory, type IIC (KIF1A)