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Neuropathy, hereditary sensory and autonomic, type 2B(HSAN2B)

MedGen UID:
413474
Concept ID:
C2751092
Disease or Syndrome
Synonyms: Hereditary sensory and autonomic neuropathy type IIB; HSAN2B
SNOMED CT: Hereditary sensory autonomic neuropathy type IIB (860810005)
 
Gene (location): RETREG1 (5p15.1)
 
Monarch Initiative: MONDO:0013142
OMIM®: 613115

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 descriptions

From OMIM
Hereditary sensory and autonomic neuropathy type IIB (HSAN2B) is an autosomal recessive neurologic disorder characterized by early childhood onset of distal sensory impairment usually resulting in ulceration and associated with variable autonomic features, such as hyperhidrosis and urinary incontinence. Some patients may show impaired gait (summary by Ilgaz Aydinlar et al., 2014). HSAN2A (201300) is caused by mutation in the HSN2 isoform of the WNK1 gene (WNK1/HSN2; see 605232). For a discussion of genetic heterogeneity of HSAN, see HSAN1 (162400).  http://www.omim.org/entry/613115
From MedlinePlus Genetics
Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch to the brain. These sensations are impaired in people with HSAN2. In some affected people, the condition may also cause mild abnormalities of the autonomic neurons, which control involuntary body functions such as heart rate, digestion, and breathing. The sensory and autonomic neurons are part of the body's peripheral nervous system, which comprises the nerves outside the brain and spinal cord. HSAN2 is considered a form of peripheral neuropathy.

The signs and symptoms of HSAN2 typically begin in infancy or early childhood. The first sign of the condition is usually numbness in the hands and feet. Soon after, affected individuals lose the ability to feel pain or sense hot and cold. In people with HSAN2, unnoticed injuries often lead to open sores (ulcers) on the hands and feet. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may require amputation of the affected area. People with HSAN2 often injure themselves unintentionally, typically by biting the tongue, lips, or fingers. These injuries may lead to loss of the affected areas, such as the tip of the tongue. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because of the inability to feel pain. Repeated injury can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are damaged.

Some people with HSAN2 lose a type of taste bud on the tip of the tongue called lingual fungiform papillae and have a diminished sense of taste.

The effects of HSAN2 on the autonomic nervous system are more variable. Some infants with HSAN2 have digestive problems such as the backflow of stomach acids into the esophagus (gastroesophageal reflux) or slow eye-blink or gag reflexes. Affected individuals may also have weak deep-tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.  https://medlineplus.gov/genetics/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Acroosteolysis
MedGen UID:
183017
Concept ID:
C0917990
Disease or Syndrome
Dissolution or degeneration of bone tissue of the phalanges of the hand.
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.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.
Episodic hyperhidrosis
MedGen UID:
387757
Concept ID:
C1857171
Finding
Intermittent episodes of abnormally increased perspiration.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Rotthier A, Baets J, De Vriendt E, Jacobs A, Auer-Grumbach M, Lévy N, Bonello-Palot N, Kilic SS, Weis J, Nascimento A, Swinkels M, Kruyt MC, Jordanova A, De Jonghe P, Timmerman V
Brain 2009 Oct;132(Pt 10):2699-711. Epub 2009 Aug 3 doi: 10.1093/brain/awp198. PMID: 19651702Free PMC Article

Recent clinical studies

Etiology

Rotthier A, Baets J, De Vriendt E, Jacobs A, Auer-Grumbach M, Lévy N, Bonello-Palot N, Kilic SS, Weis J, Nascimento A, Swinkels M, Kruyt MC, Jordanova A, De Jonghe P, Timmerman V
Brain 2009 Oct;132(Pt 10):2699-711. Epub 2009 Aug 3 doi: 10.1093/brain/awp198. PMID: 19651702Free PMC Article
Houlden H, Blake J, Reilly MM
Curr Opin Neurol 2004 Oct;17(5):569-77. doi: 10.1097/00019052-200410000-00007. PMID: 15367861
Auer-Grumbach M
Drugs Today (Barc) 2004 May;40(5):385-94. doi: 10.1358/dot.2004.40.5.850487. PMID: 15319794

Diagnosis

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
Rotthier A, Baets J, De Vriendt E, Jacobs A, Auer-Grumbach M, Lévy N, Bonello-Palot N, Kilic SS, Weis J, Nascimento A, Swinkels M, Kruyt MC, Jordanova A, De Jonghe P, Timmerman V
Brain 2009 Oct;132(Pt 10):2699-711. Epub 2009 Aug 3 doi: 10.1093/brain/awp198. PMID: 19651702Free PMC Article
Houlden H, Blake J, Reilly MM
Curr Opin Neurol 2004 Oct;17(5):569-77. doi: 10.1097/00019052-200410000-00007. PMID: 15367861
Auer-Grumbach M
Drugs Today (Barc) 2004 May;40(5):385-94. doi: 10.1358/dot.2004.40.5.850487. PMID: 15319794
Auer-Grumbach M, Wagner K, Timmerman V, De Jonghe P, Hartung HP
Neurology 2000 Jan 11;54(1):45-52. doi: 10.1212/wnl.54.1.45. PMID: 10636124

Clinical prediction guides

Bellone E, Rodolico C, Toscano A, Di Maria E, Cassandrini D, Pizzuti A, Pigullo S, Mazzeo A, Macaione V, Girlanda P, Vita G, Ajmar F, Mandich P
Neuromuscul Disord 2002 Mar;12(3):286-91. doi: 10.1016/s0960-8966(01)00282-6. PMID: 11801401
Auer-Grumbach M, Wagner K, Timmerman V, De Jonghe P, Hartung HP
Neurology 2000 Jan 11;54(1):45-52. doi: 10.1212/wnl.54.1.45. PMID: 10636124

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