The Leeds Teaching Hospitals NHS Trust

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 visit our CM panels Webpage.

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.