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Autosomal dominant Charcot–Marie–Tooth disease type 2 with giant axons

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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.

Autosomal dominant Charcot–Marie–Tooth disease type 2 with giant axons
Other namesAutosomal dominant hereditary motor and sensory neuropathy type 2 with giant axons, CMT2 with giant axons, MSN2 with giant axons.[1]
SpecialtyMedical genetics, Neurology
Symptomsmainly characterized by neurologic/sensory anomalies
Usual onsetEarly
DurationLifelong
CausesGenetic mutation
PreventionNone
PrognosisMedium
Frequencyrare, about 10-20 or more cases from 2 families have been described
Deaths2 (known)

Signs and symptoms edit

This condition is characterized by the wasting and consequent weakness of the muscles in the distal extremities of the limbs with accompanying loss of sensory sensation of said limb extremities, early-onset high foot arch, and swelling of the nerve axons with neurofilament accumulation. Additional findings include gait anomalies, muscle cramps, toe anomalies, mild cardiomyopathy, and hypo/arreflexia.[2]

Complications edit

Although this condition doesn't usually progress, the cardiomyopathy that comes along with some cases can be deadly.[3]

Causes edit

This condition is caused by autosomal dominant missense mutations in the DCAF8 gene, located in the long arm of chromosome 1.[4]

This mutation was found in a family previously reported in medical literature (by Vogel et al.) who was later examined by Klein et al. Through in-vitro funcional expression assays done in HEK293 cells, it was found that the mutant R317C protein significantly decreases the binding of DCAF8 to DDB1, which ended up negatively impacting the recruitment of the E3 ubiquitin ligase complex.

Diagnosis edit

This condition can be diagnosed by using methods (mainly) such as genetic testing, physical examination and nerve biopsy.

Epidemiology edit

According to OMIM,[5] more than 10 cases (probably closer to 20) have been described in medical literature: 9 members from a 5-generation German family[6] and an Italian family whose number of affected members isn't specified.[7]

It's estimated prevalence is less than 1 case per million people.[8]

References edit

  1. ^ "Autosomal dominant Charcot-Marie-Tooth disease type 2 with giant axons".
  2. ^ "Autosomal dominant Charcot-Marie-Tooth disease type 2 with giant axons - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2022-06-19.
  3. ^ Klein, Christopher J.; Wu, Yanhong; Vogel, Peter; Goebel, Hans H.; Bönnemann, Carsten; Zukosky, Kristen; Botuyan, Maria-Victoria; Duan, Xiaohui; Middha, Sumit; Atkinson, Elizabeth J.; Mer, Georges (2014-03-11). "Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with giant axons". Neurology. 82 (10): 873–878. doi:10.1212/WNL.0000000000000206. ISSN 1526-632X. PMC 3959756. PMID 24500646.
  4. ^ Klein, Christopher J.; Wu, Yanhong; Vogel, Peter; Goebel, Hans H.; Bönnemann, Carsten; Zukosky, Kristen; Botuyan, Maria-Victoria; Duan, Xiaohui; Middha, Sumit; Atkinson, Elizabeth J.; Mer, Georges (2014-03-11). "Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with giant axons". Neurology. 82 (10): 873–878. doi:10.1212/WNL.0000000000000206. ISSN 0028-3878. PMC 3959756. PMID 24500646.
  5. ^ "OMIM Entry - # 610100 - GIANT AXONAL NEUROPATHY 2, AUTOSOMAL DOMINANT; GAN2". omim.org. Retrieved 2022-06-19.
  6. ^ Vogel, P.; Gabriel, M.; Goebel, H. H.; Dyck, P. J. (1985-05-01). "Hereditary motor sensory neuropathy type II with neurofilament accumulation: new finding or new disorder?". Annals of Neurology. 17 (5): 455–461. doi:10.1002/ana.410170507. ISSN 0364-5134. PMID 3859241. S2CID 43815939.
  7. ^ Lus, G.; Nelis, E.; Jordanova, A.; Löfgren, A.; Cavallaro, T.; Ammendola, A.; Melone, M. a. B.; Rizzuto, N.; Timmerman, V.; Cotrufo, R.; De Jonghe, P. (2003-10-14). "Charcot-Marie-Tooth disease with giant axons: a clinicopathological and genetic entity". Neurology. 61 (7): 988–990. doi:10.1212/wnl.61.7.988. ISSN 1526-632X. PMID 14557576. S2CID 27067624.
  8. ^ "Orphanet: Autosomal dominant Charcot Marie Tooth disease type 2 with giant axons". www.orpha.net. Retrieved 2022-06-19.
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