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Hereditary hyperekplexia

MedGen UID:
332019
Concept ID:
C1835614
Disease or Syndrome
Synonym: Hyperexplexia, hereditary
SNOMED CT: Hereditary hyperekplexia (724351008); Congenital stiff man syndrome (724351008); Familial startle disease (724351008); Hereditary hyperexplexia (724351008); Kok disease (724351008); Stiff baby syndrome (724351008)
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 dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related genes: ATAD1, GPHN, SLC6A5, GLRB, GLRA1
 
Monarch Initiative: MONDO:0021022
OMIM®: 149400
OMIM® Phenotypic series: PS149400
Orphanet: ORPHA3197

Definition

A hereditary neurological disorder with characteristics of excessive startle responses. The disease manifests shortly after birth with violent jerking to noise and touch, and massive and sustained stiffening of the trunk and limbs, clenching fists, and attacks of a high frequency trembling. Motor milestones are often mildly delayed, but intellectual development is usually normal. Mutations in the GLRA1 gene (5q32) are found in about 30% of patients. These mutations are transmitted as an autosomal dominant or recessive trait. The GLRA1 gene encodes the alpha1 subunit of the juvenile neuronal receptor for the inhibitory neurotransmitter, glycine. Mutations of this subunit cause a variety of dysfunctions of the neuronal chloride (Cl-) channel. Mutations in the GLRB, GPHN and SLC6A5 genes (4q31.3, 14q24 and 11p15.2-p15.1) have also been observed. [from SNOMEDCT_US]

Professional guidelines

PubMed

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Muscle Nerve 2023 Oct;68(4):356-374. Epub 2023 Jul 11 doi: 10.1002/mus.27922. PMID: 37432872
Chia NH, McKeon A, Dalakas MC, Flanagan EP, Bower JH, Klassen BT, Dubey D, Zalewski NL, Duffy D, Pittock SJ, Zekeridou A
Ann Clin Transl Neurol 2023 Jul;10(7):1083-1094. Epub 2023 May 22 doi: 10.1002/acn3.51791. PMID: 37212351Free PMC Article

Recent clinical studies

Etiology

Aldhilan A, Alhakeem A, Al Hajjaj S, Abukhalid M, Aldhalaan H, Salah E, Saeed M, Tabassum S, El Khashab HY, Aljabri M, Ali ES, Alwadei A, Hundallah K, Alghamdi A, Hakami W, AlShafi S, Alkuraya FS, Alanazy N, Seidahmed MZ, Alfadhel M, Tabarki B
Pediatr Neurol 2022 Sep;134:78-82. Epub 2022 Jun 24 doi: 10.1016/j.pediatrneurol.2022.06.015. PMID: 35841715
Zhan FX, Wang SG, Cao L
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Brain 2018 Jan 1;141(1):13-36. doi: 10.1093/brain/awx189. PMID: 29053777Free PMC Article
Bhidayasiri R, Truong DD
Handb Clin Neurol 2011;100:421-30. doi: 10.1016/B978-0-444-52014-2.00032-X. PMID: 21496599
Tijssen MA, Voorkamp LM, Padberg GW, van Dijk JG
Arch Neurol 1997 Apr;54(4):388-93. doi: 10.1001/archneur.1997.00550160034012. PMID: 9109739

Diagnosis

Han L, Shan Q
ACS Chem Neurosci 2021 Sep 15;12(18):3397-3409. Epub 2021 Aug 30 doi: 10.1021/acschemneuro.1c00386. PMID: 34460217
Neupert DG, Rathke KM, Mikati MA
Neurology 2021 Nov 30;97(22):e2248-e2249. Epub 2021 Jul 15 doi: 10.1212/WNL.0000000000012538. PMID: 34266921
Saini AG, Pandey S
J Neurol Sci 2020 Sep 15;416:117051. Epub 2020 Jul 20 doi: 10.1016/j.jns.2020.117051. PMID: 32721683
Bhidayasiri R, Truong DD
Handb Clin Neurol 2011;100:421-30. doi: 10.1016/B978-0-444-52014-2.00032-X. PMID: 21496599
Meinck HM
Neurophysiol Clin 2006 Sep-Dec;36(5-6):357-64. Epub 2007 Jan 26 doi: 10.1016/j.neucli.2006.12.007. PMID: 17336782

Therapy

Rudrabhatla PK, Divya KP, Fasaludeen A, Menon RN, Cherian A, Urulangodi M, Sundaram S
Clin Pediatr (Phila) 2024 Jul;63(7):885-888. Epub 2023 Oct 29 doi: 10.1177/00099228231203300. PMID: 37899614
Seale J, Murphy J, Mantle A, Chan B
Adv Neonatal Care 2020 Feb;20(1):33-37. doi: 10.1097/ANC.0000000000000674. PMID: 31567315
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Carta E, Chung SK, James VM, Robinson A, Gill JL, Remy N, Vanbellinghen JF, Drew CJ, Cagdas S, Cameron D, Cowan FM, Del Toro M, Graham GE, Manzur AY, Masri A, Rivera S, Scalais E, Shiang R, Sinclair K, Stuart CA, Tijssen MA, Wise G, Zuberi SM, Harvey K, Pearce BR, Topf M, Thomas RH, Supplisson S, Rees MI, Harvey RJ
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Kulkarni ML, Kannan B, Mathadh P
Indian J Pediatr 2006 Dec;73(12):1109-11. doi: 10.1007/BF02763057. PMID: 17202641

Prognosis

Heinonen T, Flegel T, Müller H, Kehl A, Hundi S, Matiasek K, Fischer A, Donner J, Forman OP, Lohi H, Hytönen MK
Hum Genet 2023 Aug;142(8):1221-1230. Epub 2023 May 24 doi: 10.1007/s00439-023-02571-z. PMID: 37222814Free PMC Article
Ferraroli E, Perulli M, Veredice C, Contaldo I, Quintiliani M, Ricci M, Venezia I, Citrigno L, Qualtieri A, Spadafora P, Cavalcanti F, Battaglia DI
Pediatr Neurol 2022 Jul;132:45-49. Epub 2022 May 17 doi: 10.1016/j.pediatrneurol.2022.05.002. PMID: 35636282
Kulkarni ML, Kannan B, Mathadh P
Indian J Pediatr 2006 Dec;73(12):1109-11. doi: 10.1007/BF02763057. PMID: 17202641

Clinical prediction guides

Heinonen T, Flegel T, Müller H, Kehl A, Hundi S, Matiasek K, Fischer A, Donner J, Forman OP, Lohi H, Hytönen MK
Hum Genet 2023 Aug;142(8):1221-1230. Epub 2023 May 24 doi: 10.1007/s00439-023-02571-z. PMID: 37222814Free PMC Article
Ferraroli E, Perulli M, Veredice C, Contaldo I, Quintiliani M, Ricci M, Venezia I, Citrigno L, Qualtieri A, Spadafora P, Cavalcanti F, Battaglia DI
Pediatr Neurol 2022 Jul;132:45-49. Epub 2022 May 17 doi: 10.1016/j.pediatrneurol.2022.05.002. PMID: 35636282
Bogdanik LP, Chapman HD, Miers KE, Serreze DV, Burgess RW
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Recent systematic reviews

Ferraroli E, Perulli M, Veredice C, Contaldo I, Quintiliani M, Ricci M, Venezia I, Citrigno L, Qualtieri A, Spadafora P, Cavalcanti F, Battaglia DI
Pediatr Neurol 2022 Jul;132:45-49. Epub 2022 May 17 doi: 10.1016/j.pediatrneurol.2022.05.002. PMID: 35636282

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