Cerebral Malformations
Testing Summary
| Test Level | Test | Target Reporting Time* | Cost |
|---|---|---|---|
| 1 | Sequence and dosage analysis of entire gene panel | 80 days | Contact laboratory |
| 2 | Testing for known mutation(s) in a family member | 10 days | Contact laboratory |
*Target reporting times are in calendar days. For further information, see About our Reports.
Note: One or more genes can be omitted from analysis if required and bespoke testing for selected genes is also available, please contact the laboratory to discuss testing requirements and costs.
Genes and Disorders (ref. CM panel v.3.0)
| Gene | OMIM number | Disease (Inheritance Pattern) | OMIM disease number | Reference sequence |
| ACTB | *102630 | Baraitser-Winter syndrome 1 (AD) | #243310 | NM_001101.3/LRG_781t2 |
| ACTG1 | *102560 | Baraitser-Winter syndrome 2 (AD) | #614583 | NM_001614.3 |
| ADGRG1 (aka GPR56) | *604110 | Polymicrogyria, bilateral frontoparietal (AR) | #606854 | NM_005682.6 |
| AKT3 | *611223 | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (AD) | #615937 | NM_005465.4 |
| ARFGEF2 | *605371 | Periventricular heterotopia with microcephaly (AR) | #608097 | NM_006420.2 |
| ARX | *300382 | Lissencephaly, X-linked 2 (XL) | #300215 | NM_139058.2 |
| CASK | *300172 | Mental retardation and microcephaly with pontine and cerebellar hypoplasia (XL) | #300749 | NM_003688.3 |
| CCND2 | *123833 | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (AD) | #615938 | NM_001759.3 |
| DCX | *300121 | Lissencephaly, X-linked (XL) | #300067 | NM_178152.2 |
| DYNC1H1 | *600112 | Mental retardation, autosomal dominant 13 (AD) | #614563 | NM_001376.4 |
| ERMARD | *615532 | Periventricular nodular heterotopia 6 (AD) | #615544 | NM_018341.2 |
| FKRP | *606596 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 (AR) | #613153 | NM_024301.4/LRG_761t1 |
| FKTN | *607440 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (AR) | #253800 | NM_006731.2/LRG_434t2 |
| FLNA | *300017 | Heterotopia, periventricular (XL) | #300049 | NM_001110556.1 |
| GPSM2 | *609245 | Chudley-McCullough syndrome (AR) | #604213 | NM_013296.4 |
| ISPD | *614631 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (AR) | #614643 | NM_001101426.3 |
| KIF1BP (aka KIAA1279) | *609367 | Goldberg-Shprintzen megacolon syndrome (AR) | #609460 | NM_015634.3 |
| KIF2A | *602591 | Cortical dysplasia, complex, with other brain malformations 3 (AD) | #615411 | NM_004520.4 |
| KIF5C | *604593 | Cortical dysplasia, complex, with other brain malformations 2 (AD) | #615282 | NM_004522.2 |
| LAMA2 | *156225 | Muscular dystrophy, congenital merosin-deficient (AR) | #607855 | NM_000426.3/LRG_409t1 |
| LAMB1 | *150240 | Lissencephaly 5 (AR) | #615191 | NM_002291.2 |
| LAMC3 | *604349 | Cortical malformations, occipital (AR) | #614115 | NM_006059.3 |
| LARGE | *603590 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6 (AR) | #613154 | NM_004737.4/LRG_856t1 |
| NDE1 | *609449 | Lissencephaly 4 (with microcephaly) (AR) | #614019 | NM_001143979.1 |
| OCLN | *602876 | Band-like calcification with simplified gyration and polymicrogyria (AR) | #251290 | NM_002538.3 |
| OPHN1 | *300127 | Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance (XL) | #300486 | NM_002547.2 |
| PAFAH1B1 | *601545 | Lissencephaly 1 (AD) | #607432 | NM_000430.3 |
| PIK3CA | *171834 | Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic (AD) | #602501 | NM_006218.2/LRG_310t1 |
| PIK3R2 | *603157 | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (AD) | #603387 | NM_005027.3 |
| POMGNT1 | *606822 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 (AR) | #253280 | NM_017739.3 |
| POMT1 | *607423 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (AR) | #236670 | NM_007171.3 |
| POMT2 | *607439 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 (AR) | #613150 | NM_013382.5 |
| RELN | *600514 | Lissencephaly 2 (Norman-Roberts type) (AR) | #257320 | NM_005045.3 |
| RTTN | *610436 | Polymicrogyria with seizures (AR) | #614833 | NM_173630.3 |
| SRPX2 | *300642 | ?Rolandic epilepsy, mental retardation, and speech dyspraxia (XL) | #300643 | NM_014467.2 |
| TMEM5 | *605862 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10 (AR) | #615041 | NM_014254.2 |
| TUBA1A | *602529 | Lissencephaly 3 (AD) | #611603 | NM_006009.3 |
| TUBA8 | *605742 | Polymicrogyria with optic nerve hypoplasia (AR) | #613180 | NM_018943.2 |
| TUBB | *191130 | Cortical dysplasia, complex, with other brain malformations 6 (AD) | #615771 | NM_178014.3 |
| TUBB2A | *615101 | Cortical dysplasia, complex, with other brain malformations 5 (AD) | #615763 | NM_001069.2 |
| TUBB2B | *612850 | Polymicrogyria, symmetric or asymmetric (AD) | #610031 | NM_178012.4 |
| TUBB3 | *602661 | Cortical dysplasia, complex, with other brain malformations 1 (AD) | #614039 | NM_006086.3 |
| TUBG1 | *191135 | Cortical dysplasia, complex, with other brain malformations 4 (AD) | #615412 | NM_001070.4 |
| VLDLR | *192977 | Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 (AR) | #224050 | NM_003383.3 |
| WDR62 | *613583 | Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (AR) | #604317 | NM_001083961.1 |
For previous versions of the cerebral malformations panel please see here.
Acceptable referrers
Clinical geneticists
Neurologists (adult & paediatric)
Clinical Description and Genes Involved
Cerebral malformation disorders are genetic diseases with a neurological (and sometimes structural) phenotype characterised by abnormal structure of the cerebral cortex of the brain, usually visualised on MRI.
Mutations in the genes involved in this panel can cause a variety of cortical malformations including lissencephaly, subcortical band heterotopia, pachygyria, agyria and polymicrogyria. There is a degree of clinical and neuroradiological overlap between some of these disorders. Possible diagnoses are generally determined by brain imaging, and the input of neurologists is essential.
Inheritance patterns of the disorders associated with these genes are variable; some are X-linked, some are autosomal dominant, and some are autosomal recessive. We recommend that the families of patients referred for this test are also referred to a Clinical Genetics department where it is appropriate to do so. In some cases, testing of parents is strongly recommended to inform clinical significance of potential de novo sequence variants.
This assay does not detect polyalanine expansions in the ARX gene, associated with early infantile epileptic encephalopathy, Partington syndrome and X-linked mental retardation without brain malformations. Samples for patients with these ARX-related disorders may be sent to the All-Wales Molecular Genetics Service, Cardiff.
We request that all cases are provided with full clinical details, and a summary of any neuroradiological findings. This is essential for determining the clinical relevance of any genetic variants. Failure to provide these details may result in delays in reporting results, and/or results with limited clinical interpretation.
