Lissencephaly is a rare, genetically heterogeneous brain malformation caused by impaired neuronal migration during embryogenesis. The condition is characterized by absence or incomplete development of the gyri of the brain cortex, causing a smooth brain surface. Other typical findings include an abnormally thick, poorly organized cortex, postnatal microcephaly, profound mental retardation, severe developmental delay, and seizures. Milder forms are associated with infrequent seizures and intellectual disability.
The lissencephaly and related disorders NGS panel consists of forty-two genes: ACTB, ACTG1, ADGRG1, ARX, ATP6V0A2, B3GALNT2, B4GAT1, CDK5, DAG1, DCX, DYNC1H1, FKRP, FKTN, GMPPB, ISPD, KATNB1, KIF2A, KIF5C, LAMA2, LAMB1, LARGE1, NDE1, PAFAH1B1, POMGNT1, POMGNT2, POMK, POMT1, POMT2, RELN, RXYLT1, SNAP29, SRD5A3, TMTC3, TUBA1A, TUBA8, TUBB, TUBB2A, TUBB2B, TUBB3, TUBG1, VLDLR and WDR62.
Copy number variation (CNV) analysis of the lissencephaly and related disorder genes is also offered as a panel. Additionally, CTGT offers a comprehensive test (both NGS and CNV panels) for these genes. Panel genes are also offered as individual sequencing and deletion/duplication tests, unless otherwise indicated.
Gene |
Disorder |
MIM |
Inheritance |
ACTB |
Baraitser-Winter syndrome 1 (BRWS1) |
243310 |
AD |
ACTG1 |
Baraitser-Winter syndrome 2 (BRWS2) |
614583 |
AD |
ADGRG1 |
Polymicrogyria, bilateral frontoparietal (BFPP) Polymicrogyria, bilateral perisylvian, autosomal recessive (BPPR) |
606854 615752 |
AR AR |
ARX |
Lissencephaly, X-linked 2, (LISX2) |
300215 |
XL |
ATP6V0A2 |
Cutis laxa, autosomal recessive, type IIA (ARCL2A) |
219200 |
AR |
B3GALNT2 |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11 (MDDGA11) |
615181 |
AR |
B4GAT1 |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 (MDDGA13) |
615287 |
AR |
CDK5 |
Lissencephaly 7 with cerebellar hypoplasia (LIS7) |
616342 |
AR |
DAG1 |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9 (MDDGA9) |
616538 |
AR |
DCX |
Lissencephaly, X-linked, 1 (LISX1) |
300067 |
XL |
DYNC1H1 |
Mental retardation, autosomal dominant 13 (MRD13) |
614563 |
AD |
FKRP |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 (MDDGA5) Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5 (MDDGB5) |
613153 606612 |
AR AR |
FKTN |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (MDDGA4) |
253800 |
AR |
GMPPB |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MDDGA14) Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 (MDDGB14) |
615350 615351 |
AR AR |
ISPD |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (MDDGA7) |
614643 |
AR |
KATNB1 |
Lissencephaly 6 with microcephaly (LIS6) |
616212 |
AR |
KIF2A |
Cortical dysplasia, complex, with other brain malformations 3 (CDCBM3) |
615411 |
AD |
KIF5C |
Cortical dysplasia, complex, with other brain malformations 2 (CDCBM2) |
615282 |
AD |
LAMA2 |
Muscular dystrophy, congenital merosin-deficient, 1A (MDC1A) |
607855 |
AR |
LAMB1 |
Lissencephaly 5 (LIS5) |
615191 |
AR |
LARGE1 |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6 (MDDGA6) Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6 (MDDGB6) |
613154 608840 |
AR AR |
NDE1 |
Lissencephaly 4 (LIS4) Microhydranencephaly (MHAC) |
614019 605013 |
AR AR |
PAFAH1B1 |
Lissencephaly 1 (LIS1) |
607432 |
AD |
POMGNT1 |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 (MDDGA3) |
253280 |
AR |
POMGNT2 |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 (MDDGA2) |
613150 |
AR |
POMK |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 (MDDGA12) |
615249 |
AR |
POMT1 |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (MDDGA1) |
236670 |
AR |
POMT2 |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 (MDDGA2) |
613150 |
AR |
RELN |
Lissencephaly 2 (LIS2) |
257320 |
AR |
RXYLT1 |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10 (MDDGA10) |
615041 |
AR |
SNAP29 |
Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome |
609528 |
AR |
SRD5A3 |
Congenital disorder of glycosylation, type Iq (CDG1Q) |
612379 |
AR |
TMTC3 |
Lissencephaly 8 (LIS8) |
617255 |
AR |
TUBA1A |
Lissencephaly 3 (LIS3) |
611603 |
AD |
TUBA8 |
Cortical dysplasia, complex, with other brain malformations 8 (CDCBM8) |
613180 |
AR |
TUBB |
Cortical dysplasia, complex, with other brain malformations 6 (CDCBM6) |
615771 |
AD |
TUBB2A |
Cortical dysplasia, complex, with other brain malformations 5 (CDCBM5) |
615763 |
AD |
TUBB2B |
Cortical dysplasia, complex, with other brain malformations 7 (CDCBM7) |
610031 |
AD |
TUBB3 |
Cortical dysplasia, complex, with other brain malformations 1 (CDCBM1) |
614039 |
AD |
TUBG1 |
Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) |
615412 |
AD |
VLDLR |
Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 (CAMRQ1) |
224050 |
AR |
WDR62 |
Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (MCPH2) |
604317 |
AR |
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