Genetics and mechanisms leading to human cortical malformations

Romero, Delfina M.; Bahi‐Buisson, Nadia; Francis, Fiona

doi:10.1016/j.semcdb.2017.09.031

Cited by 100 publications

(118 citation statements)

References 400 publications

(486 reference statements)

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“…New neurons of the developing cortex proliferate in the ventricular zone, then divide asymmetrically, and migrate in an inward‐out pattern to populate the cortex where they differentiate, form axons and dendrites, and establish patterned connections with other neurons . Malformations of cortical development can thus be classified as defects in proliferation, migration, or connectivity, on the basis of which of those processes is (most) affected . Defects in proliferation and migration result in brain abnormalities that can be visible prenatally, whereas connectivity defects primarily cause functional deficits resulting in such conditions as intellectual disability, autism, and epilepsies.…”

Section: Malformations Of Cortical Developmentmentioning

confidence: 99%

“…Many of the known genes mutated in these conditions encode cytoskeletal proteins, tubulin subunits, and kinesins. These mutations produce diverse conditions that can present with a combination of heterotopias, gyration abnormalities, other CNS abnormalities, and extracranial structural defects . Early prenatal detection is challenging because neuronal migration and cortical folding occurs in the late second and third trimester of fetal development and because of the limitations of ultrasound.…”

Section: Disorders Of Neuronal Migrationmentioning

confidence: 99%

“…SBH is caused by heterozygous mutations in females in the X‐linked DCX gene, encoding doublecortin. Affected girls and women have focal or generalized seizures and normal intelligence, mild learning disability, or intellectual disability of variable severity, depending on the severity of the mutation, X‐inactivation, and mosaicism . When women transmit the DCX mutation to males, it causes classic lissencephaly (see below) .…”

Section: Disorders Of Neuronal Migrationmentioning

confidence: 99%

“…Classical lissencephaly affects 1.2:100 000 births and is characterized by a smooth thick disorganized four‐layer cortex and absence of deep sulci and gyri, the result of neuronal undermigration, with absence of other major brain anomalies. It can be divided into six grades from mild (grade 6) to complete agyria (grade 1) . There are three main genes for classic lissencephaly: The first is LIS1 ( PAFAH1B1 ) in 17p13.3.…”

Section: Disorders Of Neuronal Migrationmentioning

confidence: 99%

“…This is often due to a microdeletion, which is de novo in 80% and inherited from a parent with a balanced translocation in 20%, but other LIS1 mutations have been found in isolated lissencephaly. A second common cause of classic lissencephaly is mutations in DCX in Xq22.3 in males, of whom 25% inherit the mutation from their mother and the remainder are caused by de novo mutations . Mutations in these two genes cause 76% of all lissencephaly and mutations in TUBA1A cause an additional 4% .…”

Section: Disorders Of Neuronal Migrationmentioning

confidence: 99%

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Prenatally diagnosed developmental abnormalities of the central nervous system and genetic syndromes: A practical review

Veyver

2019

Prenatal Diagnosis

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Developmental brain abnormalities are complex and can be difficult to diagnose by prenatal imaging because of the ongoing growth and development of the brain throughout pregnancy and the limitations of ultrasound, often requiring fetal magnetic resonance imaging as an additional tool. As for all major structural congenital anomalies, amniocentesis with chromosomal microarray and a karyotype is the first‐line recommended test for the genetic work‐up of prenatally diagnosed central nervous system (CNS) abnormalities. Many CNS defects, especially neuronal migration defects affecting the cerebral and cerebellar cortex, are caused by single‐gene mutations in a large number of different genes. Early data suggest that prenatal diagnostic exome sequencing for fetal CNS defects will have a high diagnostic yield, but interpretation of sequencing results can be complex. Yet a genetic diagnosis is important for prognosis prediction and recurrence risk counseling. The evaluation and management of such patients is best done in a multidisciplinary team approach. Here, we review general principles of the genetic work‐up for fetuses with CNS defects and review categories of genetic causes of prenatally diagnosed CNS phenotypes.

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Section: Malformations Of Cortical Developmentmentioning

confidence: 99%

Section: Disorders Of Neuronal Migrationmentioning

confidence: 99%

Section: Disorders Of Neuronal Migrationmentioning

confidence: 99%

Section: Disorders Of Neuronal Migrationmentioning

confidence: 99%

Section: Disorders Of Neuronal Migrationmentioning

confidence: 99%

See 3 more Smart Citations

Prenatally diagnosed developmental abnormalities of the central nervous system and genetic syndromes: A practical review

Veyver

2019

Prenatal Diagnosis

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Basics and Terminology

2022

Medical Genetics and Genomics

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Central nervous system involvement in arthrogryposis multiplex congenita: Overview of causes, diagnosis, and care

Dieterich

Kimber

Hall

2019

American J of Med Genetics Pt C

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Arthrogryposis or AMC, arthrogryposis multiplex congenita, is defined as multiple congenital joint contractures in more than two joints and in different body areas. The common cause of all AMC is lack of movement in utero, which in turn can have different causes, one of which is CNS involvement. Intellectual disability/CNS involvement is found in approximately 25% of all AMC. AMC with CNS involvement includes a large number of genetic syndromes. So far, more than 400 genes have been identified as linked to AMC, with and without CNS involvement. A number of neonatally lethal syndromes and syndromes resulting in severe disability due to CNS malfunction belong to this group of syndromes. There are several X-linked disorders with AMC, which are primarily related to intellectual disability. A number of neuromuscular disorders may include AMC and CNS/brain involvement. Careful clinical evaluation by a geneticist and a pediatrician/pediatric neurologist is the first step in making a specific diagnosis.Further investigations may include MRI of the brain and spinal cord, electroencephalogram, blood chemistry for muscle enzymes, other organ investigations (ophtalmology, cardiology, gastrointestinal, and genitourinary systems). Nerve conduction studies, electromyogram, and muscle pathology may be of help when there is associated peripheral nervous system involvement. But most importantly, genetic investigations with targeted or rather whole exome or genome sequencing should be performed. A correct diagnosis is important in planning adequate treatment, in genetic counselling and also for future understanding of pathogenic mechanisms and possible new treatments.A multidiciplinary team is needed both in investigation and treatment. K E Y W O R D Sarthrogryposis multiplex congenita, neonatally lethal AMC syndromes, central nervous system involvement, multi-organ involvement, intellectual disability

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Genetics and mechanisms leading to human cortical malformations

Cited by 100 publications

References 400 publications

Prenatally diagnosed developmental abnormalities of the central nervous system and genetic syndromes: A practical review

Prenatally diagnosed developmental abnormalities of the central nervous system and genetic syndromes: A practical review

Basics and Terminology

Central nervous system involvement in arthrogryposis multiplex congenita: Overview of causes, diagnosis, and care

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