Genetic epilepsy syndromes
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
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