Autosomal recessive axonal neuropathy with neuromyotonia

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Autosomal recessive axonal neuropathy with neuromyotonia
Other namesGamstorp-Wohlfart syndrome, Myokymia, myotonia, and muscle wasting, ARAN-NM, ARCMT2-NM, Autosomal recessive Charcot-Marie-Tooth disease type 2 with neuromyotonia, NMAN [1]
Autorecessive.svg
Specialty Medical genetics

Autosomal recessive axonal neuropathy with neuromyotonia, also known as Gamstorp-Wohlfart syndrome, is a rare hereditary disorder which is characterized by progressive poly-neuropathy, neuromyotonia, myokymia, pseudo-myotonia, hand-foot contractures, and abnormal neuro-myotonic/myokimic activity visible on needle EMG. [2] According to OMIM, around 52 cases have been reported in medical literature [3] However; new cases (mostly from Europe and North America) have been reported since 2014. [4] [5] [6] [7]

Contents

Presentation

People with this disorder usually show the following symptoms: axonal neuropathy, atrophy (wasting/degeneration) of the muscles in the hands, feet and legs, chronic muscular weakness which is very apparent when exercise is being done, abnormal gait, high chance of accidental falls, and joint contractures, neuromyotonia, and myokymia. In some people, the axonal neuropathy ends up reducing their sensitivity to cold and hot temperatures and touch in the distal parts of the arms and legs. [8] [9] Some of the symptoms worsen temporarily when a person with this disorder is exposed to cold temperatures. [10]

Causes

This disorder is caused by a homozygous mutation in the HINT1 gene, in chromosome 5 (c.334 C > A, p.H112 N). [11]

Diagnosis

Etimology

This condition was discovered in 1991 by Hahn et al., when they described two Chinese-Canadian siblings of the opposite sex. The male had difficulties releasing his grip, childhood-onset neuromyotonia and muscle stiffness, progressive motor neuropathy, finger cramping while and after writing, involuntary twitches of the finger, thigh and forearm muscles, foot drop-associated gait problems, hand weakness, hyporeflexia, and tongue percussion, his younger sister wasn't as affected as his brother, she only shared some of his symptoms, these include; upper and lower distal muscle weakness. Both siblings were revealed to have a chronic motor neuropathy, peripheral nerve fiber hyperexcitability, and multiple denervations. Muscle biopsies performed in the brother detected chronic partial denervation. [12]

Through the siblings reported by Hahn et al. and 50 new patients from 33 families across the world, it was found that this disorder is caused by HINT1 mutations. [13]

Related Research Articles

<span class="mw-page-title-main">Charcot–Marie–Tooth disease</span> Neuromuscular disease

Charcot–Marie–Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. This disease is the most commonly inherited neurological disorder, affecting about one in 2,500 people. It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925).

<span class="mw-page-title-main">Spinal muscular atrophies</span> Muscular degenerative disorders caused by dysfunction of spinal neurons

Spinal muscular atrophies (SMAs) are a genetically and clinically heterogeneous group of rare debilitating disorders characterised by the degeneration of lower motor neurons and subsequent atrophy (wasting) of various muscle groups in the body. While some SMAs lead to early infant death, other diseases of this group permit normal adult life with only mild weakness.

<span class="mw-page-title-main">Giant axonal neuropathy</span> Medical condition

Giant axonal neuropathy is a rare, autosomal recessive neurological disorder that causes disorganization of neurofilaments. Neurofilaments form a structural framework that helps to define the shape and size of neurons and are essential for normal nerve function. A distinguishing feature is its association with kinky, or curly, hair; in such cases it has been called Giant axonal neuropathy with curly hair.

Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.

<span class="mw-page-title-main">Behr syndrome</span> Medical condition

Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay.

<span class="mw-page-title-main">Congenital muscular dystrophy</span> Medical condition

Congenital muscular dystrophies are autosomal recessively-inherited muscle diseases. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges from myopathic to overtly dystrophic due to the age at which the biopsy takes place.

<span class="mw-page-title-main">Dejerine–Sottas disease</span> Medical condition

Dejerine–Sottas disease, also known as, Dejerine–Sottas syndrome, hereditary motor and sensory polyneuropathy type III, and Charcot–Marie–Tooth disease type 3, is a hereditary neurological disorder characterized by damage to the peripheral nerves, demyelination, and resulting progressive muscle wasting and somatosensory loss. The condition is caused by mutations in various genes and currently has no known cure.

<span class="mw-page-title-main">Familial amyloid polyneuropathy</span> Medical condition

Familial amyloid polyneuropathy, also called transthyretin-related hereditary amyloidosis, transthyretin amyloidosis abbreviated also as ATTR, or Corino de Andrade's disease, is an autosomal dominant neurodegenerative disease. It is a form of amyloidosis, and was first identified and described by Portuguese neurologist Mário Corino da Costa Andrade, in 1952. FAP is distinct from senile systemic amyloidosis (SSA), which is not inherited, and which was determined to be the primary cause of death for 70% of supercentenarians who have been autopsied. FAP can be ameliorated by liver transplantation.

<span class="mw-page-title-main">Bethlem myopathy</span> Medical condition

Bethlem myopathy is predominantly an autosomal dominant myopathy, classified as a congenital form of limb-girdle muscular dystrophy. There are two types of Bethlem myopathy, based on which type of collagen is affected.

<span class="mw-page-title-main">Hereditary motor and sensory neuropathy</span> Medical condition

Hereditary motor and sensory neuropathies (HMSN) is a name sometimes given to a group of different neuropathies which are all characterized by their impact upon both afferent and efferent neural communication. HMSN are characterised by atypical neural development and degradation of neural tissue. The two common forms of HMSN are either hypertrophic demyelinated nerves or complete atrophy of neural tissue. Hypertrophic condition causes neural stiffness and a demyelination of nerves in the peripheral nervous system, and atrophy causes the breakdown of axons and neural cell bodies. In these disorders, a patient experiences progressive muscle atrophy and sensory neuropathy of the extremities.

Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation.

<span class="mw-page-title-main">X-linked spinal muscular atrophy type 2</span> Medical condition

X-linked spinal muscular atrophy type 2, also known as arthrogryposis multiplex congenita X-linked type 1 (AMCX1), is a rare neurological disorder involving death of motor neurons in the anterior horn of spinal cord resulting in generalised muscle wasting (atrophy). The disease is caused by a mutation in UBA1 gene and is passed in an X-linked recessive manner by carrier mothers to affected sons.

<span class="mw-page-title-main">Hereditary neuropathy with liability to pressure palsy</span> Medical condition

Hereditary neuropathy with liability to pressure palsy (HNPP) is a peripheral neuropathy, a condition that affects the nerves. Pressure on the nerves can cause tingling sensations, numbness, pain, weakness, muscle atrophy and even paralysis of the affected area. In normal individuals, these symptoms disappear quickly, but in sufferers of HNPP even a short period of pressure can cause the symptoms to occur. Palsies can last from minutes or days to weeks or even months.

<span class="mw-page-title-main">Congenital fiber type disproportion</span> Medical condition

Congenital fiber type disproportion (CFTD) is an inherited form of myopathy with small type 1 muscle fibers that may occur in a number of neurological disorders. It has a relatively good outcome and follows a stable course. While the exact genetics is unclear, there is an association with mutations in the genes TPM3, ACTA1 and SELENON. It is a rare condition.

Congenital distal spinal muscular atrophy (cDSMA), also known as distal hereditary motor neuropathytype VIII (dHMN8), is a hereditary medical condition characterized by muscle wasting (atrophy), particularly of distal muscles in legs and hands, and by early-onset contractures of the hip, knee, and ankle. Affected individuals often have shorter lower limbs relative to the trunk and upper limbs. The condition is a result of a loss of anterior horn cells localized to lumbar and cervical regions of the spinal cord early in infancy, which in turn is caused by a mutation of the TRPV4 gene. The disorder is inherited in an autosomal dominant manner. Arm muscle and function, as well as cardiac and respiratory functions are typically well preserved.

Distal hereditary motor neuropathy type V is a particular type of neuropathic disorder. In general, distal hereditary motor neuropathies affect the axons of distal motor neurons and are characterized by progressive weakness and atrophy of muscles of the extremities. It is common for them to be called "spinal forms of Charcot-Marie-Tooth disease (CMT)", because the diseases are closely related in symptoms and genetic cause. The diagnostic difference in these diseases is the presence of sensory loss in the extremities. There are seven classifications of dHMNs, each defined by patterns of inheritance, age of onset, severity, and muscle groups involved. Type V is a disorder characterized by autosomal dominance, weakness of the upper limbs that is progressive and symmetrical, and atrophy of the small muscles of the hands.

<span class="mw-page-title-main">Andermann syndrome</span> Medical condition

Andermann syndrome, also known as agenesis of corpus callosum with neuronopathy (ACCPN), Charlevoix disease and KCC3 axonopathy among other names, is a very rare neurodegenerative genetic disorder that damages the nerves used to control muscles and related to sensation and is often associated with agenesis of the corpus callosum.

Kahrizi syndrome (KHRZ) is an autosomal-recessive disease that is identified by mental retardation, cataracts, coloboma, kyphosis, and coarse facial features caused by a homozygous mutation in the SRD5A3 gene.

Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, also known as SANDO syndrome, is a very rare genetic disorder which is characterized by ocular and nerve anomalies.

Autosomal dominant Charcot–Marie–Tooth disease type 2 with giant axons is a rare subtype of hereditary motor and sensory neuropathy of the axons which is characterized by symptoms similar to those from Charcot–Marie–Tooth disease and autosomal dominant inheritance.

References

  1. "Autosomal recessive axonal neuropathy with neuromyotonia".
  2. RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Autosomal recessive axonal neuropathy with neuromyotonia". www.orpha.net. Retrieved 2022-05-25.{{cite web}}: CS1 maint: numeric names: authors list (link)
  3. "OMIM Entry - # 137200 - NEUROMYOTONIA AND AXONAL NEUROPATHY, AUTOSOMAL RECESSIVE; NMAN". omim.org. Retrieved 2022-05-25.
  4. Caetano, Joana Serra; Costa, Carmen; Baets, Jonathan; Zimon Phd, Madgalena; Venâncio Phd, Margarida; Saraiva Phd, Jorge; Negrão, Luís; Fineza, Isabel (January 2014). "Autosomal recessive axonal neuropathy with neuromyotonia: a rare entity". Pediatric Neurology. 50 (1): 104–107. doi:10.1016/j.pediatrneurol.2013.08.028. ISSN   1873-5150. PMID   24131582.
  5. Jerath, Nivedita U.; Shy, Michael E.; Grider, Tiffany; Gutmann, Ludwig (December 2015). "A case of neuromyotonia and axonal motor neuropathy: A report of a HINT1 mutation in the United States". Muscle & Nerve. 52 (6): 1110–1113. doi:10.1002/mus.24774. ISSN   1097-4598. PMID   26182879. S2CID   19535873.
  6. Meng, Lingchao; Fu, Jun; Lv, He; Zhang, Wei; Wang, Zhaoxia; Yuan, Yun (August 2018). "Novel mutations in HINT1 gene cause autosomal recessive axonal neuropathy with neuromyotonia in two cases of sensorimotor neuropathy and one case of motor neuropathy". Neuromuscular Disorders. 28 (8): 646–651. doi:10.1016/j.nmd.2018.05.003. ISSN   1873-2364. PMID   30001929. S2CID   51619784.
  7. Rauchenzauner, Markus; Frühwirth, Martin; Hecht, Martin; Kofler, Markus; Witsch-Baumgartner, Martina; Fauth, Christine (April 2016). "A Novel Variant in the HINT1 Gene in a Girl with Autosomal Recessive Axonal Neuropathy with Neuromyotonia: Thorough Neurological Examination Gives the Clue". Neuropediatrics. 47 (2): 119–122. doi:10.1055/s-0035-1570493. ISSN   1439-1899. PMID   26760849. S2CID   40598133.
  8. "Autosomal recessive axonal neuropathy with neuromyotonia: MedlinePlus Genetics". medlineplus.gov. Retrieved 2022-05-25.
  9. Peeters, Kristien; Chamova, Teodora; Tournev, Ivailo; Jordanova, Albena (2017-04-01). "Axonal neuropathy with neuromyotonia: there is a HINT". Brain. 140 (4): 868–877. doi:10.1093/brain/aww301. ISSN   0006-8950. PMC   5382946 . PMID   28007994.
  10. "Autosomal recessive axonal neuropathy with neuromyotonia - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2022-05-25.
  11. Caetano, Joana Serra; Costa, Carmen; Baets, Jonathan; Zimon PhD, Madgalena; Venâncio PhD, Margarida; Saraiva PhD, Jorge; Negrão, Luís; Fineza, Isabel (2014-01-01). "Autosomal Recessive Axonal Neuropathy With Neuromyotonia: A Rare Entity". Pediatric Neurology. 50 (1): 104–107. doi:10.1016/j.pediatrneurol.2013.08.028. ISSN   0887-8994. PMID   24131582.
  12. Hahn, A. F.; Parkes, A. W.; Bolton, C. F.; Stewart, S. A. (March 1991). "Neuromyotonia in hereditary motor neuropathy". Journal of Neurology, Neurosurgery, and Psychiatry. 54 (3): 230–235. doi:10.1136/jnnp.54.3.230. ISSN   0022-3050. PMC   1014391 . PMID   1851512.
  13. Zimoń, Magdalena; Baets, Jonathan; Almeida-Souza, Leonardo; De Vriendt, Els; Nikodinovic, Jelena; Parman, Yesim; Battaloğlu, Esra; Matur, Zeliha; Guergueltcheva, Velina; Tournev, Ivailo; Auer-Grumbach, Michaela (October 2012). "Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia". Nature Genetics. 44 (10): 1080–1083. doi:10.1038/ng.2406. ISSN   1546-1718. PMID   22961002. S2CID   205345993.