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Neuropathy, hereditary sensory, type 2C(HSN2C)

MedGen UID:
481798
Concept ID:
C3280168
Disease or Syndrome
Synonym: Hereditary sensory and autonomic neuropathy type IIC
 
Gene (location): KIF1A (2q37.3)
 
Monarch Initiative: MONDO:0013634
OMIM®: 614213

Disease characteristics

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]
Authors:
Ingo Kurth   view full author information

Additional description

From OMIM
HSN2C is an autosomal recessive disorder characterized by onset in the first decade of progressive distal sensory loss leading to ulceration and amputation of the fingers and toes. Affected individuals also develop distal muscle weakness, primarily affecting the lower limbs (summary by Riviere et al., 2011). For a discussion of genetic heterogeneity of HSN, see HSAN1 (162400).  http://www.omim.org/entry/614213

Clinical features

From HPO
Distal lower limb muscle weakness
MedGen UID:
324514
Concept ID:
C1836450
Finding
Reduced strength of the distal musculature of the legs.
Autoamputation of digits
MedGen UID:
343770
Concept ID:
C1852289
Finding
The spontaneous detachment of a digit (finger or toe) from the body due to long standing pathology.
Areflexia of lower limbs
MedGen UID:
347285
Concept ID:
C1856694
Finding
Inability to elicit tendon reflexes in the lower limbs.
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Hypoesthesia
MedGen UID:
6974
Concept ID:
C0020580
Finding
Decreased ability to perceive touch.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Impaired distal vibration sensation
MedGen UID:
381262
Concept ID:
C1853767
Finding
A decrease in the ability to perceive vibration in the distal portions of the limbs.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Impaired distal proprioception
MedGen UID:
867227
Concept ID:
C4021585
Finding
A loss or impairment of the sensation of the relative position of parts of the body and joint position occurring at distal joints.
Intrinsic hand muscle atrophy
MedGen UID:
351202
Concept ID:
C1864716
Finding
Atrophy of the intrinsic muscle groups of the hand, comprising the thenar and hypothenar muscles; the interossei muscles; and the lumbrical muscles.
Acral ulceration
MedGen UID:
1648438
Concept ID:
C4732740
Finding
A type of digital ulcer that manifests as an open sore on the surface of the skin at the tip of a finger or toe.

Recent clinical studies

Etiology

Barešić A, Peričić Salihović M
Genet Test Mol Biomarkers 2014 Feb;18(2):83-7. Epub 2013 Nov 4 doi: 10.1089/gtmb.2013.0323. PMID: 24180318Free PMC Article
Unger S, Lausch E, Stanzial F, Gillessen-Kaesbach G, Stefanova I, Di Stefano CM, Bertini E, Dionisi-Vici C, Nilius B, Zabel B, Superti-Furga A
Am J Med Genet A 2011 Nov;155A(11):2860-4. Epub 2011 Sep 30 doi: 10.1002/ajmg.a.34268. PMID: 21964829
Deng HX, Klein CJ, Yan J, Shi Y, Wu Y, Fecto F, Yau HJ, Yang Y, Zhai H, Siddique N, Hedley-Whyte ET, Delong R, Martina M, Dyck PJ, Siddique T
Nat Genet 2010 Feb;42(2):165-9. Epub 2009 Dec 27 doi: 10.1038/ng.509. PMID: 20037587Free PMC Article
Klein CJ, Cunningham JM, Atkinson EJ, Schaid DJ, Hebbring SJ, Anderson SA, Klein DM, Dyck PJ, Litchy WJ, Thibodeau SN, Dyck PJ
Neurology 2003 Apr 8;60(7):1151-6. doi: 10.1212/01.wnl.0000055900.30217.ea. PMID: 12682323
Nagamatsu M, Jenkins RB, Schaid DJ, Klein DM, Dyck PJ
Arch Neurol 2000 May;57(5):669-72. doi: 10.1001/archneur.57.5.669. PMID: 10815132

Diagnosis

Chen H, Sun C, Zheng Y, Yin J, Gao M, Zhao C, Lin J
BMC Neurol 2023 Jun 30;23(1):250. doi: 10.1186/s12883-023-03260-0. PMID: 37391745Free PMC Article
Taşdelen E, Calame DG, Akay G, Mitani T, Fatih JM, Herman I, Du H, Coban-Akdemir Z, Marafi D, Jhangiani SN, Posey JE, Gibbs RA, Altıparmak T, Kutlay NY, Lupski JR, Pehlivan D
Am J Med Genet A 2022 Jul;188(7):2153-2161. Epub 2022 Mar 24 doi: 10.1002/ajmg.a.62727. PMID: 35332675Free PMC Article
Nam DE, Nam SH, Lee AJ, Hong YB, Choi BO, Chung KW
J Peripher Nerv Syst 2018 Mar;23(1):60-66. Epub 2018 Feb 6 doi: 10.1111/jns.12249. PMID: 29341343
Klein CJ, Cunningham JM, Atkinson EJ, Schaid DJ, Hebbring SJ, Anderson SA, Klein DM, Dyck PJ, Litchy WJ, Thibodeau SN, Dyck PJ
Neurology 2003 Apr 8;60(7):1151-6. doi: 10.1212/01.wnl.0000055900.30217.ea. PMID: 12682323
Nagamatsu M, Jenkins RB, Schaid DJ, Klein DM, Dyck PJ
Arch Neurol 2000 May;57(5):669-72. doi: 10.1001/archneur.57.5.669. PMID: 10815132

Prognosis

Nam DE, Nam SH, Lee AJ, Hong YB, Choi BO, Chung KW
J Peripher Nerv Syst 2018 Mar;23(1):60-66. Epub 2018 Feb 6 doi: 10.1111/jns.12249. PMID: 29341343
Unger S, Lausch E, Stanzial F, Gillessen-Kaesbach G, Stefanova I, Di Stefano CM, Bertini E, Dionisi-Vici C, Nilius B, Zabel B, Superti-Furga A
Am J Med Genet A 2011 Nov;155A(11):2860-4. Epub 2011 Sep 30 doi: 10.1002/ajmg.a.34268. PMID: 21964829
Klein CJ, Cunningham JM, Atkinson EJ, Schaid DJ, Hebbring SJ, Anderson SA, Klein DM, Dyck PJ, Litchy WJ, Thibodeau SN, Dyck PJ
Neurology 2003 Apr 8;60(7):1151-6. doi: 10.1212/01.wnl.0000055900.30217.ea. PMID: 12682323

Clinical prediction guides

Kikuchi JK, Nagashima Y, Mano T, Ishiura H, Hayashi T, Shimizu J, Matsukawa T, Ichikawa Y, Takahashi Y, Karino S, Kanbayashi T, Kira J, Goto J, Tsuji S
J Mol Neurosci 2021 Sep;71(9):1796-1801. Epub 2021 Jan 12 doi: 10.1007/s12031-020-01784-5. PMID: 33433851
Nam DE, Nam SH, Lee AJ, Hong YB, Choi BO, Chung KW
J Peripher Nerv Syst 2018 Mar;23(1):60-66. Epub 2018 Feb 6 doi: 10.1111/jns.12249. PMID: 29341343
Unger S, Lausch E, Stanzial F, Gillessen-Kaesbach G, Stefanova I, Di Stefano CM, Bertini E, Dionisi-Vici C, Nilius B, Zabel B, Superti-Furga A
Am J Med Genet A 2011 Nov;155A(11):2860-4. Epub 2011 Sep 30 doi: 10.1002/ajmg.a.34268. PMID: 21964829
Klein CJ, Cunningham JM, Atkinson EJ, Schaid DJ, Hebbring SJ, Anderson SA, Klein DM, Dyck PJ, Litchy WJ, Thibodeau SN, Dyck PJ
Neurology 2003 Apr 8;60(7):1151-6. doi: 10.1212/01.wnl.0000055900.30217.ea. PMID: 12682323

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