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Hypomyelination neuropathy-arthrogryposis syndrome

MedGen UID:
1647504
•Concept ID:
C4707882
•
Disease or Syndrome
Synonym: Hypomyelination neuropathy arthrogryposis syndrome
SNOMED CT: Hypomyelination neuropathy arthrogryposis syndrome (766931003)
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)
 
Orphanet: ORPHA2680

Definition

A rare genetic limb malformation syndrome with characteristics of multiple congenital distal joint contractures (including talipes equinovarus and both proximal and distal interphalangeal joint contractures of the hands) and very severe motor paralysis at birth (such as lack of swallowing, autonomous respiratory function and deep tendon reflexes), leading to death within first 3 months of life. Fetal hypo or akinesia, late-onset polyhydramnios and dramatically reduced, or absent, motor nerve conduction velocities are frequently associated. Nerve ultrastructural morphology shows severe abnormalities of the nodes of Ranvier and myelinated axons. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHypomyelination neuropathy-arthrogryposis syndrome

Professional guidelines

PubMed

SPTAN1 encephalopathy: distinct phenotypes and genotypes.
Tohyama J, Nakashima M, Nabatame S, Gaik-Siew C, Miyata R, Rener-Primec Z, Kato M, Matsumoto N, Saitsu H
J Hum Genet 2015 Apr;60(4):167-73. Epub 2015 Jan 29 doi: 10.1038/jhg.2015.5. PMID: 25631096
Further genotype-phenotype correlation emerging from two families with PLP1 exon 4 skipping.
Biancheri R, Grossi S, Regis S, Rossi A, Corsolini F, Rossi DP, Cavalli P, Severino M, Filocamo M
Clin Genet 2014 Mar;85(3):267-72. Epub 2013 May 27 doi: 10.1111/cge.12154. PMID: 23711321
Cerebral folate deficiency and folinic acid treatment in hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) syndrome.
Mercimek-Mahmutoglu S, Stockler-Ipsiroglu S
Tohoku J Exp Med 2007 Jan;211(1):95-6; author reply 97. doi: 10.1620/tjem.211.95. PMID: 17202777

Recent clinical studies

Etiology

An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Leukodystrophies and genetic leukoencephalopathies in children.
Sarret C
Rev Neurol (Paris) 2020 Jan-Feb;176(1-2):10-19. Epub 2019 Jun 4 doi: 10.1016/j.neurol.2019.04.003. PMID: 31174885
Hypomyelinating leukodystrophies - a molecular insight into the white matter pathology.
Charzewska A, Wierzba J, Iżycka-Świeszewska E, Bekiesińska-Figatowska M, Jurek M, Gintowt A, Kłosowska A, Bal J, Hoffman-Zacharska D
Clin Genet 2016 Oct;90(4):293-304. Epub 2016 Jun 17 doi: 10.1111/cge.12811. PMID: 27234264
ERCC6 dysfunction presenting as progressive neurological decline with brain hypomyelination.
Shehata L, Simeonov DR, Raams A, Wolfe L, Vanderver A, Li X, Huang Y, Garner S, Boerkoel CF, Thurm A, Herman GE, Tifft CJ, He M, Jaspers NG, Gahl WA
Am J Med Genet A 2014 Nov;164A(11):2892-900. Epub 2014 Sep 22 doi: 10.1002/ajmg.a.36709. PMID: 25251875Free PMC Article
Congenital cataracts-facial dysmorphism-neuropathy.
Kalaydjieva L
Orphanet J Rare Dis 2006 Aug 29;1:32. doi: 10.1186/1750-1172-1-32. PMID: 16939648Free PMC Article

Diagnosis

Neurodevelopmental Disorder Caused by Deletion of CHASERR, a lncRNA Gene.
Ganesh VS, Riquin K, Chatron N, Yoon E, Lamar KM, Aziz MC, Monin P, O'Leary MC, Goodrich JK, Garimella KV, England E, Weisburd B, Aguet F, Bacino CA, Murdock DR, Dai H, Rosenfeld JA, Emrick LT, Ketkar S, Sarusi Y, Sanlaville D, Kayani S, Broadbent B, Pengam A, Isidor B, Bezieau S, Cogné B, MacArthur DG, Ulitsky I, Carvill GL, O'Donnell-Luria A
N Engl J Med 2024 Oct 24;391(16):1511-1518. doi: 10.1056/NEJMoa2400718. PMID: 39442041
Brain imaging findings in Liberfarb syndrome: hypomyelination and optic nerve and cerebellar atrophy.
Pinto E, Pinto C, Ramos C, Alves JE
Pediatr Radiol 2023 Mar;53(3):561-563. Epub 2022 Sep 22 doi: 10.1007/s00247-022-05503-7. PMID: 36136119
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Leukodystrophies and genetic leukoencephalopathies in children.
Sarret C
Rev Neurol (Paris) 2020 Jan-Feb;176(1-2):10-19. Epub 2019 Jun 4 doi: 10.1016/j.neurol.2019.04.003. PMID: 31174885
Leukoencephalopathies associated with macrocephaly.
Renaud DL
Semin Neurol 2012 Feb;32(1):34-41. Epub 2012 Mar 15 doi: 10.1055/s-0032-1306384. PMID: 22422204

Therapy

Effects of endocrine disrupting chemicals on myelin development and diseases.
Naffaa V, Laprévote O, Schang AL
Neurotoxicology 2021 Mar;83:51-68. Epub 2020 Dec 29 doi: 10.1016/j.neuro.2020.12.009. PMID: 33352275
Mutations in ACTL6B, coding for a subunit of the neuron-specific chromatin remodeling complex nBAF, cause early onset severe developmental and epileptic encephalopathy with brain hypomyelination and cerebellar atrophy.
Fichera M, Failla P, Saccuzzo L, Miceli M, Salvo E, Castiglia L, Galesi O, Grillo L, Calì F, Greco D, Amato C, Romano C, Elia M
Hum Genet 2019 Feb;138(2):187-198. Epub 2019 Jan 17 doi: 10.1007/s00439-019-01972-3. PMID: 30656450
Overcoming Monocarboxylate Transporter 8 (MCT8)-Deficiency to Promote Human Oligodendrocyte Differentiation and Myelination.
Lee JY, Kim MJ, Deliyanti D, Azari MF, Rossello F, Costin A, Ramm G, Stanley EG, Elefanty AG, Wilkinson-Berka JL, Petratos S
EBioMedicine 2017 Nov;25:122-135. Epub 2017 Oct 19 doi: 10.1016/j.ebiom.2017.10.016. PMID: 29111262Free PMC Article
Control of seizures by ketogenic diet-induced modulation of metabolic pathways.
Clanton RM, Wu G, Akabani G, Aramayo R
Amino Acids 2017 Jan;49(1):1-20. Epub 2016 Sep 28 doi: 10.1007/s00726-016-2336-7. PMID: 27683025
Hypomyelination with atrophy of the basal ganglia and cerebellum in an infant with Down syndrome.
Narumi Y, Shiihara T, Yoshihashi H, Sakazume S, van der Knaap MS, Nishimura-Tadaki A, Matsumoto N, Fukushima Y
Clin Dysmorphol 2011 Jul;20(3):166-167. doi: 10.1097/MCD.0b013e32834659a8. PMID: 21471810

Prognosis

The atypical sphingolipid SPB 18:1(14Z);O2 is a biomarker for DEGS1 related hypomyelinating leukodystrophy.
Hülsmeier AJ, Toelle SP, Bellstedt P, Wentzel C, Bahr A, Kolokotronis K, Hornemann T
J Lipid Res 2023 Dec;64(12):100464. Epub 2023 Oct 27 doi: 10.1016/j.jlr.2023.100464. PMID: 37890668Free PMC Article
Effects of endocrine disrupting chemicals on myelin development and diseases.
Naffaa V, Laprévote O, Schang AL
Neurotoxicology 2021 Mar;83:51-68. Epub 2020 Dec 29 doi: 10.1016/j.neuro.2020.12.009. PMID: 33352275
Monocarboxylate Transporter 8 Deficiency: Delayed or Permanent Hypomyelination?
Vancamp P, Demeneix BA, Remaud S
Front Endocrinol (Lausanne) 2020;11:283. Epub 2020 May 13 doi: 10.3389/fendo.2020.00283. PMID: 32477268Free PMC Article
Congenital cataracts-facial dysmorphism-neuropathy.
Kalaydjieva L
Orphanet J Rare Dis 2006 Aug 29;1:32. doi: 10.1186/1750-1172-1-32. PMID: 16939648Free PMC Article
Clinical and genetic description of a family with Charcot-Marie-Tooth disease type 1B from a transmembrane MPZ mutation.
Eggers SD, Keswani SC, Melli G, Cornblath DR
Muscle Nerve 2004 Jun;29(6):867-9. doi: 10.1002/mus.20034. PMID: 15170620

Clinical prediction guides

Brain imaging findings in Liberfarb syndrome: hypomyelination and optic nerve and cerebellar atrophy.
Pinto E, Pinto C, Ramos C, Alves JE
Pediatr Radiol 2023 Mar;53(3):561-563. Epub 2022 Sep 22 doi: 10.1007/s00247-022-05503-7. PMID: 36136119
Aberrant Oligodendrogenesis in Down Syndrome: Shift in Gliogenesis?
Reiche L, Küry P, Göttle P
Cells 2019 Dec 7;8(12) doi: 10.3390/cells8121591. PMID: 31817891Free PMC Article
Amino acid synthesis deficiencies.
de Koning TJ
J Inherit Metab Dis 2017 Jul;40(4):609-620. Epub 2017 Jun 26 doi: 10.1007/s10545-017-0063-1. PMID: 28653176Free PMC Article
Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia.
Minnerop M, Kurzwelly D, Wagner H, Soehn AS, Reichbauer J, Tao F, Rattay TW, Peitz M, Rehbach K, Giorgetti A, Pyle A, Thiele H, Altmüller J, Timmann D, Karaca I, Lennarz M, Baets J, Hengel H, Synofzik M, Atasu B, Feely S, Kennerson M, Stendel C, Lindig T, Gonzalez MA, Stirnberg R, Sturm M, Roeske S, Jung J, Bauer P, Lohmann E, Herms S, Heilmann-Heimbach S, Nicholson G, Mahanjah M, Sharkia R, Carloni P, Brüstle O, Klopstock T, Mathews KD, Shy ME, de Jonghe P, Chinnery PF, Horvath R, Kohlhase J, Schmitt I, Wolf M, Greschus S, Amunts K, Maier W, Schöls L, Nürnberg P, Zuchner S, Klockgether T, Ramirez A, Schüle R
Brain 2017 Jun 1;140(6):1561-1578. doi: 10.1093/brain/awx095. PMID: 28459997Free PMC Article
Congenital cataracts-facial dysmorphism-neuropathy.
Kalaydjieva L
Orphanet J Rare Dis 2006 Aug 29;1:32. doi: 10.1186/1750-1172-1-32. PMID: 16939648Free PMC Article

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