IllnessNeuropathy, hereditary sensory + autonomous - HSN/HSAN; differential diagnosis

NGS +

The hereditary sensory and autonomic neuropathies (HSAN) represent a genetically and clinically heterogeneous group of neurodegenerative disorders of the peripheral nervous system. Clinical descriptions of HSAN are somewhat inconsistent, possibly as result of reports lacking molecular genetic confirmation of the diagnosis. The group of HSAN1A to HSAN1F is an autosomal dominantly inherited, genetically heterogeneous disorder defined by the five mutated genes. The HSAN2A to HSAN2D group is characterized by a progressive reduction in pain, temperature and touch sensation and is caused by mutations in four different genes. HSAN3 (familial dysautonomia, Riley-Day syndrome) is caused by pathogenic variants in ELP1 and is inherited in an autosomal recessive manner. HSAN4 as congenital insensitivity to pain with anhidrosis results from pathogenic variants in NTRK1. It is characterized by profound sensory loss, primarily affecting the perception of pain and temperature. HSAN5 shows clear clinical overlap with HSAN4 and is caused by pathogenic variants either in the NGF or NTRK1 genes. HSAN6 is characterized by dysautonomic symptoms and a mutated DST1 gene. Clinically closely related appears congenital pain insensitivity caused by two additional mutated genes (SCN9A, SCN11A) as well as CMT2B (RAB7A mutations). The molecular genetic diagnostic yield differs greatly between HSAN groups or is mostly unknown. Therefore, a negative DNA result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK49247/

• Alias: HSAN
• Alias: HSN
• Alias: Polyneuropathie
• Allelic: Episodic pain syndrome, familial, 3 (SCN11A)
• Allelic: Erythermalgia, primary (SCN9A)
• Allelic: Febrile seizures, familial, 3B (SCN9A)
• Allelic: Generalized epilepsy with febrile seizures plus, type 7 (SCN9A)
• Allelic: Mucopolysaccharidosis type IIIB [Sanfilippo B] (NAGLU)
• Allelic: NESCAV syndrome (KIF1A)
• Allelic: Paroxysmal extreme pain disorder (SCN9A)
• Allelic: Pseudohypoaldosteronism, type IIC (WNK1)
• Allelic: Spastic paraplegia 30, AD + AR (KIF1A)
• Achalasia-addisonianism-alacrimia syndrome (AAAS)
• Alacrima, achalasia + mental retardation syndrome (GMPPA)
• Amyloidosis, hereditary, transthyretin-related (TTR)
• Ataxia, posterior column, with retinitis pigmentosa (FLVCR1)
• Carpal tunnel syndrome, familial (TTR)
• Charcot-Marie-Tooth disease, axonal, type 2V (NAGLU)
• Dysautonomia, familial (ELP1 syn. IKBKAP)
• Dystransthyretinemic hyperthyroxinemia (TTR)
• Episodic pain syndrome, familial, 1 (TRPA1)
• Episodic pain syndrome, familial, 2 (SCN10A)
• Fabry disease (GLA)
• Insensitivity to pain, congenital (SCN9A)
• Insensitivity to pain, congenital, with anhidrosis (NTRK1)
• Neuropathy, hereditary sensory + autonomic, type IA (SPTLC1)
• Neuropathy, hereditary sensory + autonomic, type IC (SPTLC2)
• Neuropathy, hereditary sensory + autonomic, type II (WNK1)
• Neuropathy, hereditary sensory + autonomic, type IIB (RETREG1 syn. FAM134B)
• Neuropathy, hereditary sensory + autonomic, type IID (SCN9A)
• Neuropathy, hereditary sensory + autonomic, type V (NGF)
• Neuropathy, hereditary sensory + autonomic, type VI (DST)
• Neuropathy, hereditary sensory + autonomic, type VII (SCN11A)
• Neuropathy, hereditary sensory, type IIC (KIF1A)
• Small fiber neuropathy (SCN9A)
• Spastic paraplegia 61, AR (ARL6IP1)