Early onset or syndromic epilepsy
Gene: ARX
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Polyalanine tract expansion (exon 2) in addition to missense, nonesense, frameshift variants etc. phenotypic spectrum of disorders caused by a variant in the ARX gene, comprising a nearly continuous series of developmental disorders ranging from MR (Partington syndrome), hrdanencephaly and lissencephaly (LISX2), Proud syndrome and XLR EIEE1 - these final 2 are both associated with seizures. Males with ARX mutations are often more severely affected, female mutation carriers may also be affected. Lots of reported cases - OMIM and HGMD Pro. Functional studies - Shoubridge et al, 2012.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Epileptic encephalopathy, early infantile, 1, 308350; Hydranencephaly with abnormal genitalia,300215 ; Lissencephaly, X-linked 2, 300215; Mental retardation, X-linked 29, 300419; Partington syndrome,309510; Proud syndrome, 300004
Publications
Comment on mode of inheritance: The revised mode of inheritance fits with gene2phenotype of hemizygous inheritance for this disorder.Created: 17 Dec 2015, 12:32 p.m.
Comment on mode of inheritance: Discussion with reviewer determined that females require two mutations to develop this disorder (X-linked recessive).Created: 17 Dec 2015, 11:43 a.m.
Where females manifest it would be due to x-skewing. Is this the right option?Created: 12 Nov 2015, 1:50 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Epileptic encephalopathy, early infantile, 1; Lissencephaly, X-linked 2; Mental retardation, X-linked, with or without seizures, ARX-related; Partington syndrome; Proud syndrome
Publications
Variants in this GENE are reported as part of current diagnostic practice
Where females manifest it would be due to x-skewing. Is this the right option?Created: 12 Nov 2015, 1:14 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Epileptic encephalopathy, early infantile, 1; Lissencephaly, X-linked 2; Mental retardation, X-linked, with or without seizures, ARX-related; Partington syndrome; Proud syndrome
Publications
Variants in this GENE are reported as part of current diagnostic practice
Where females manifest it would be due to x-skewing. Is this the right option?Created: 12 Nov 2015, 1:04 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Epileptic encephalopathy, early infantile, 1; Lissencephaly, X-linked 2; Mental retardation, X-linked, with or without seizures, ARX-related; Partington syndrome; Proud syndrome
Publications
Variants in this GENE are reported as part of current diagnostic practice
Where females manifest it would be due to x-skewing. Is this the right option?Created: 12 Nov 2015, 12:26 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Epileptic encephalopathy, early infantile, 1; Lissencephaly, X-linked 2; Mental retardation, X-linked, with or without seizures, ARX-related; Partington syndrome; Proud syndrome
Publications
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: ARX were set to Tsurusaki et al (2002) Nature 30: 441-445; Kato et al (2004) Hum Mut 23: 147-159; Bienvenu et al (2002) Hum Mol Genet 11(8): 981-991; Partington et al (1998) Am J Med Genet 30: 251-262; 35094084
Publications for gene: ARX were set to Tsurusaki et al (2002) Nature 30: 441-445; Kato et al (2004) Hum Mut 23: 147-159; Bienvenu et al (2002) Hum Mol Genet 11(8): 981-991; Partington et al (1998) Am J Med Genet 30: 251-262
Source Wessex and West Midlands GLH was added to ARX.
Source NHS GMS was added to ARX.
Richard Scott: Where females manifest it woul
Phenotypes for gene: ARX were changed from to Epileptic encephalopathy, early infantile, 1 308350; Hydranencephaly with abnormal genitalia 300215; Lissencephaly, X-linked 2 300215; Mental retardation, X-linked 29 and others 300419; Partington syndrome 309510; Proud syndrome 300004
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to ARX. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to ARX. Panel: Genetic Epilepsy Syndromes
ARX was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert,Radboud University Medical Center, Nijmegen,UKGTN
ARX was created by Sarah Leigh