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Hereditary sensory and autonomic neuropathy type 2

MedGen UID:
1800880
•Concept ID:
C5574675
•
Disease or Syndrome
Synonyms: Giaccai type acroosteolysis; Hereditary sensory and autonomic neuropathy type II; Hereditary sensory neuropathy type 2; Hereditary sensory radicular neuropathy, recessive form; HSN Type II; Morvan disease; Neurogenic acroosteolysis; Neuropathy, congenital sensory; Neuropathy, progressive sensory, of children
SNOMED CT: Hereditary sensory and autonomic neuropathy type II (398148000); Hereditary sensory and autonomic neuropathy, type II (398148000); Painless whitlow disease (398148000); Dominant hereditary sensory neuropathy, type II (398148000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Related genes: WNK1, RETREG1, SCN9A, KIF1A
 
Monarch Initiative: MONDO:0019941
Orphanet: ORPHA970

Disease characteristics

Excerpted from the GeneReview: Hereditary Sensory and Autonomic Neuropathy Type II
Hereditary sensory and autonomic neuropathy type II (HSAN2) is characterized by progressively reduced sensation to pain, temperature, and touch. Onset can be at birth and is often before puberty. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Unnoticed injuries and neuropathic skin promote ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Painless fractures can complicate the disease. Autonomic disturbances are variable and can include hyperhidrosis, tonic pupils, and urinary incontinence in those with more advanced disease. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Ingo Kurth   view full author information

Professional guidelines

PubMed

Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy.
Adams D, Ando Y, Beirão JM, Coelho T, Gertz MA, Gillmore JD, Hawkins PN, Lousada I, Suhr OB, Merlini G
J Neurol 2021 Jun;268(6):2109-2122. Epub 2020 Jan 6 doi: 10.1007/s00415-019-09688-0. PMID: 31907599Free PMC Article
Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations.
Kazachkov M, Palma JA, Norcliffe-Kaufmann L, Bar-Aluma BE, Spalink CL, Barnes EP, Amoroso NE, Balou SM, Bess S, Chopra A, Condos R, Efrati O, Fitzgerald K, Fridman D, Goldenberg RM, Goldhaber A, Kaufman DA, Kothare SV, Levine J, Levy J, Lubinsky AS, Maayan C, Moy LC, Rivera PJ, Rodriguez AJ, Sokol G, Sloane MF, Tan T, Kaufmann H
Respir Med 2018 Aug;141:37-46. Epub 2018 Jun 21 doi: 10.1016/j.rmed.2018.06.017. PMID: 30053970Free PMC Article
Molecular pathogenesis, experimental therapy and genetic counseling in hereditary sensory neuropathies.
Mroczek M, Kabzińska D, Kochański A
Acta Neurobiol Exp (Wars) 2015;75(2):126-43. doi: 10.55782/ane-2015-2023. PMID: 26232991

Recent clinical studies

Etiology

Expanding the Knowledge of KIF1A-Dependent Disorders to a Group of Polish Patients.
Paprocka J, Jezela-Stanek A, Śmigiel R, Walczak A, Mierzewska H, Kutkowska-Kaźmierczak A, Płoski R, Emich-Widera E, Steinborn B
Genes (Basel) 2023 Apr 25;14(5) doi: 10.3390/genes14050972. PMID: 37239332Free PMC Article
Heterozygous KIF1A variants underlie a wide spectrum of neurodevelopmental and neurodegenerative disorders.
Nicita F, Ginevrino M, Travaglini L, D'Arrigo S, Zorzi G, Borgatti R, Terrone G, Catteruccia M, Vasco G, Brankovic V, Siliquini S, Romano S, Veredice C, Pedemonte M, Armando M, Lettori D, Stregapede F, Bosco L, Sferra A, Tessarollo V, Romaniello R, Ristori G, Bertini E, Valente EM, Zanni G
J Med Genet 2021 Jul;58(7):475-483. Epub 2020 Jul 31 doi: 10.1136/jmedgenet-2020-107007. PMID: 32737135
Carriers of recessive WNK1/HSN2 mutations for hereditary sensory and autonomic neuropathy type 2 (HSAN2) are more sensitive to thermal stimuli.
Loggia ML, Bushnell MC, Tétreault M, Thiffault I, Bhérer C, Mohammed NK, Kuchinad AA, Laferrière A, Dicaire MJ, Loisel L, Mogil JS, Brais B
J Neurosci 2009 Feb 18;29(7):2162-6. doi: 10.1523/JNEUROSCI.4633-08.2009. PMID: 19228968Free PMC Article
Novel mutation in the HSN2 gene in a Korean patient with hereditary sensory and autonomic neuropathy type 2.
Cho HJ, Kim BJ, Suh YL, An JY, Ki CS
J Hum Genet 2006;51(10):905-908. Epub 2006 Sep 1 doi: 10.1007/s10038-006-0033-1. PMID: 16946995
Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians.
Roddier K, Thomas T, Marleau G, Gagnon AM, Dicaire MJ, St-Denis A, Gosselin I, Sarrazin AM, Larbrisseau A, Lambert M, Vanasse M, Gaudet D, Rouleau GA, Brais B
Neurology 2005 May 24;64(10):1762-7. doi: 10.1212/01.WNL.0000161849.29944.43. PMID: 15911806

Diagnosis

Expression pattern analysis and characterization of the hereditary sensory and autonomic neuropathy 2 A (HSAN2A) gene with no lysine kinase (WNK1) in human dorsal root ganglion.
Sapio MR, King DM, Staedtler ES, Maric D, Jahanipour J, Kurochkina NA, Manalo AP, Ghetti A, Mannes AJ, Iadarola MJ
Exp Neurol 2023 Dec;370:114552. Epub 2023 Oct 2 doi: 10.1016/j.expneurol.2023.114552. PMID: 37793538
A novel nonsense mutation in WNK1/HSN2 associated with sensory neuropathy and limb destruction in four siblings of a large Iranian pedigree.
Rahmani B, Fekrmandi F, Ahadi K, Ahadi T, Alavi A, Ahmadiani A, Asadi S
BMC Neurol 2018 Nov 29;18(1):195. doi: 10.1186/s12883-018-1201-6. PMID: 30497409Free PMC Article
Phosphoregulation of the Na-K-2Cl and K-Cl cotransporters by the WNK kinases.
Kahle KT, Rinehart J, Lifton RP
Biochim Biophys Acta 2010 Dec;1802(12):1150-8. Epub 2010 Jul 15 doi: 10.1016/j.bbadis.2010.07.009. PMID: 20637866Free PMC Article
Carriers of recessive WNK1/HSN2 mutations for hereditary sensory and autonomic neuropathy type 2 (HSAN2) are more sensitive to thermal stimuli.
Loggia ML, Bushnell MC, Tétreault M, Thiffault I, Bhérer C, Mohammed NK, Kuchinad AA, Laferrière A, Dicaire MJ, Loisel L, Mogil JS, Brais B
J Neurosci 2009 Feb 18;29(7):2162-6. doi: 10.1523/JNEUROSCI.4633-08.2009. PMID: 19228968Free PMC Article
Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians.
Roddier K, Thomas T, Marleau G, Gagnon AM, Dicaire MJ, St-Denis A, Gosselin I, Sarrazin AM, Larbrisseau A, Lambert M, Vanasse M, Gaudet D, Rouleau GA, Brais B
Neurology 2005 May 24;64(10):1762-7. doi: 10.1212/01.WNL.0000161849.29944.43. PMID: 15911806

Prognosis

Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians.
Roddier K, Thomas T, Marleau G, Gagnon AM, Dicaire MJ, St-Denis A, Gosselin I, Sarrazin AM, Larbrisseau A, Lambert M, Vanasse M, Gaudet D, Rouleau GA, Brais B
Neurology 2005 May 24;64(10):1762-7. doi: 10.1212/01.WNL.0000161849.29944.43. PMID: 15911806

Clinical prediction guides

Expression pattern analysis and characterization of the hereditary sensory and autonomic neuropathy 2 A (HSAN2A) gene with no lysine kinase (WNK1) in human dorsal root ganglion.
Sapio MR, King DM, Staedtler ES, Maric D, Jahanipour J, Kurochkina NA, Manalo AP, Ghetti A, Mannes AJ, Iadarola MJ
Exp Neurol 2023 Dec;370:114552. Epub 2023 Oct 2 doi: 10.1016/j.expneurol.2023.114552. PMID: 37793538
Expanding the Knowledge of KIF1A-Dependent Disorders to a Group of Polish Patients.
Paprocka J, Jezela-Stanek A, Śmigiel R, Walczak A, Mierzewska H, Kutkowska-Kaźmierczak A, Płoski R, Emich-Widera E, Steinborn B
Genes (Basel) 2023 Apr 25;14(5) doi: 10.3390/genes14050972. PMID: 37239332Free PMC Article
WNK1/HSN2 mutation in human peripheral neuropathy deregulates KCC2 expression and posterior lateral line development in zebrafish (Danio rerio).
Bercier V, Brustein E, Liao M, Dion PA, Lafrenière RG, Rouleau GA, Drapeau P
PLoS Genet 2013;9(1):e1003124. Epub 2013 Jan 3 doi: 10.1371/journal.pgen.1003124. PMID: 23300475Free PMC Article
Carriers of recessive WNK1/HSN2 mutations for hereditary sensory and autonomic neuropathy type 2 (HSAN2) are more sensitive to thermal stimuli.
Loggia ML, Bushnell MC, Tétreault M, Thiffault I, Bhérer C, Mohammed NK, Kuchinad AA, Laferrière A, Dicaire MJ, Loisel L, Mogil JS, Brais B
J Neurosci 2009 Feb 18;29(7):2162-6. doi: 10.1523/JNEUROSCI.4633-08.2009. PMID: 19228968Free PMC Article
Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians.
Roddier K, Thomas T, Marleau G, Gagnon AM, Dicaire MJ, St-Denis A, Gosselin I, Sarrazin AM, Larbrisseau A, Lambert M, Vanasse M, Gaudet D, Rouleau GA, Brais B
Neurology 2005 May 24;64(10):1762-7. doi: 10.1212/01.WNL.0000161849.29944.43. PMID: 15911806

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