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Genetic epilepsy syndromes

Region: ISCA-37430-Loss

17p13.3 (Miller-Dieker syndrome) region (includes YWHAE and PAFAH1B1) Loss

Green List (high evidence)

Chromosome: 17
GRCh38 Position: 1344539-2685615
Haploinsufficiency Score: Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score:
Required percent of overlap: 80%
Variant types: CNV Loss

1 review

Rebecca Foulger (Genomics England curator)

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. Suggested rating: Green.
Created: 15 Aug 2019, 2:43 p.m. | Last Modified: 15 Aug 2019, 2:43 p.m.
Panel Version: 1.239

Details

ISCA ID
ISCA-37430-Loss
ISCA Region Name
17p13.3 (Miller-Dieker syndrome) region (includes YWHAE and PAFAH1B1) Loss
Chromosome
17
GRCh38 Coordinates
1344539-2685615
Haploinsufficiency Score
Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score
Required percent of overlap
80%
Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • NHS GMS
  • Expert Review Green
  • ClinGen
Phenotypes
  • microcephaly, dysgenesis of the corpus callosum, and cerebellar atrophy, as well as neurobehavioral disorders, including delayed development, mental retardation, and attention deficit-hyperactivity disorder. Patients with duplications of YWHAE tended to have macrosomia, facial dysmorphism, and mild developmental delay
  • growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment
  • Chromosome 17p13.3 duplication syndrome
  • prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip, thin vermilion border, and small jaw
  • Characteristic facies, pre- and post-natal growth retardation
  • 247200
  • classic lissencephaly (pachygyria, incomplete or absent gyration of the cerebrum), microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, cardiac malformations, hypoplastic male extrenal genitalia, growth retardation, and mental deficiency with seizures and EEG abnormalities
  • Miller-Dieker lissencephaly syndrome
Clinvar variants
Variants in
Penetrance
None
Variant types
CNV Loss
Publications

History Filter Activity

15 Aug 2019, Gel status: 3

Changed Triplosensitivity Score, Added New Source

Rebecca Foulger (Genomics England curator)

Triplosensitivity Score for ISCA-37430-Loss was changed from to None. Source NHS GMS was added to Region: ISCA-37430-Loss.

11 Dec 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

11th December 2018 After extensive review and curation the Genetic epilepsy sydrome panel is ready to be promoted to Version 1.

7 Sep 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Louise Daugherty (Genomics England Curator)

Region: ISCA-37430-Loss was added Region: ISCA-37430-Loss was added to Genetic Epilepsy Syndromes. Sources: ClinGen,Expert Review Green Mode of inheritance for Region: ISCA-37430-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for Region: ISCA-37430-Loss were set to 19584063; 1671808; 1879837; 3391613; 12621583; 7634541 Phenotypes for Region: ISCA-37430-Loss were set to microcephaly, dysgenesis of the corpus callosum, and cerebellar atrophy, as well as neurobehavioral disorders, including delayed development, mental retardation, and attention deficit-hyperactivity disorder. Patients with duplications of YWHAE tended to have macrosomia, facial dysmorphism, and mild developmental delay; growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment; Chromosome 17p13.3 duplication syndrome; prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip, thin vermilion border, and small jaw; Characteristic facies, pre- and post-natal growth retardation; 247200; classic lissencephaly (pachygyria, incomplete or absent gyration of the cerebrum), microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, cardiac malformations, hypoplastic male extrenal genitalia, growth retardation, and mental deficiency with seizures and EEG abnormalities; Miller-Dieker lissencephaly syndrome