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Lissencephaly

MedGen UID:
78604
Concept ID:
C0266463
Congenital Abnormality; Finding
Synonyms: Lissencephalia; Lissencephalies
SNOMED CT: Lissencephaly (204036008); Lissencephaly pachygyria (204036008)
 
Related genes: ARX, TUBA1A, RELN, PAFAH1B1, LAMB1, DCX
 
HPO: HP:0001339
Monarch Initiative: MONDO:0018838
OMIM® Phenotypic series: PS607432
Orphanet: ORPHA48471

Definition

A spectrum of malformations of cortical development caused by insufficient neuronal migration that subsumes the terms agyria, pachygyria and subcortical band heterotopia. See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly. [from HPO]

Term Hierarchy

Conditions with this feature

Miller Dieker syndrome
MedGen UID:
78538
Concept ID:
C0265219
Disease or Syndrome
PAFAH1B1-related lissencephaly/subcortical band heterotopia (SBH) comprises a spectrum of severity. Affected newborns typically have mild-to-moderate hypotonia, feeding difficulties, and poor head control. During the first years, neurologic examination typically demonstrates poor visual tracking and response to sounds, axial hypotonia, and mild distal spasticity that can transition over time to more severe spasticity. Seizures occur in more than 90% of individuals with lissencephaly and often include infantile spasms. Seizures are often drug resistant, but even with good seizure control, the best developmental level achieved (excluding the few individuals with partial lissencephaly) is the equivalent of about age three to five months. In individuals with PAFAH1B1-related lissencephaly/SBH, developmental delay ranges from mild to severe. Other findings in PAFAH1B1-related lissencephaly/SBH include feeding issues and aspiration (which may result in need for gastrostomy tube placement), progressive microcephaly, and occasional developmental regression.
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
MedGen UID:
140820
Concept ID:
C0410174
Disease or Syndrome
Fukuyama congenital muscular dystrophy (FCMD) is characterized by hypotonia, symmetric generalized muscle weakness, and CNS migration disturbances that result in changes consistent with cobblestone lissencephaly with cerebral and cerebellar cortical dysplasia. Mild, typical, and severe phenotypes are recognized. Onset typically occurs in early infancy with poor suck, weak cry, and floppiness. Affected individuals have contractures of the hips, knees, and interphalangeal joints. Later features include myopathic facial appearance, pseudohypertrophy of the calves and forearms, motor and speech delays, intellectual disability, seizures, ophthalmologic abnormalities including visual impairment and retinal dysplasia, and progressive cardiac involvement after age ten years. Swallowing disturbance occurs in individuals with severe FCMD and in individuals older than age ten years, leading to recurrent aspiration pneumonia and death.
Norman-Roberts syndrome
MedGen UID:
163213
Concept ID:
C0796089
Disease or Syndrome
Lissencephaly with cerebellar hypoplasia (LCH) affects brain development, resulting in the brain having a smooth appearance (lissencephaly) instead of its normal folds and grooves. In addition, the part of the brain that coordinates movement is unusually small and underdeveloped (cerebellar hypoplasia). Other parts of the brain are also often underdeveloped in LCH, including the hippocampus, which plays a role in learning and memory, and the part of the brain that is connected to the spinal cord (the brainstem).\n\nIndividuals with LCH have moderate to severe intellectual disability and delayed development. They have few or no communication skills, extremely poor muscle tone (hypotonia), problems with coordination and balance (ataxia), and difficulty sitting or standing without support. Most affected children experience recurrent seizures (epilepsy) that begin within the first months of life. Some affected individuals have nearsightedness (myopia), involuntary eye movements (nystagmus), or puffiness or swelling caused by a buildup of fluids in the body's tissues (lymphedema).
X-linked lissencephaly with abnormal genitalia
MedGen UID:
375832
Concept ID:
C1846171
Disease or Syndrome
X-linked lissencephaly-2 (LISX2) is a developmental disorder characterized by structural brain anomalies, early-onset intractable seizures, severe psychomotor retardation, and ambiguous genitalia. Males are severely affected and often die within the first days or months of life, whereas females may be unaffected or have a milder phenotype (Bonneau et al., 2002). LISX2 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from hydranencephaly and lissencephaly to Proud syndrome (300004) to infantile spasms without brain malformations (DEE1; 308350) to syndromic (309510) and nonsyndromic (300419) mental retardation (Kato et al., 2004; Wallerstein et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
PEHO-like syndrome
MedGen UID:
337956
Concept ID:
C1850056
Disease or Syndrome
A rare genetic neurological disease characterized by progressive encephalopathy, early-onset seizures with a hypsarrhythmic pattern, facial and limb edema, severe hypotonia, early arrest of psychomotor development and craniofacial dysmorphism (evolving microcephaly, narrow forehead, short nose, prominent auricles, open mouth, micrognathia), in the absence of neuro-ophthalmic or neuroradiologic findings. Poor visual responsiveness, growth failure and tapering fingers are also associated. There is evidence the disease is caused by homozygous mutation in the CCDC88A gene on chromosome 2p16.
Baraitser-Winter syndrome 1
MedGen UID:
340943
Concept ID:
C1855722
Disease or Syndrome
Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a multiple congenital anomaly syndrome characterized by typical craniofacial features and intellectual disability. Many (but not all) affected individuals have pachygyria that is predominantly frontal, wasting of the shoulder girdle muscles, and sensory impairment due to iris or retinal coloboma and/or sensorineural deafness. Intellectual disability, which is common but variable, is related to the severity of the brain malformations. Seizures, congenital heart defects, renal malformations, and gastrointestinal dysfunction are also common.
Craniotelencephalic dysplasia
MedGen UID:
347462
Concept ID:
C1857471
Disease or Syndrome
Characterised by frontal encephalocoele, craniosynostosis, and developmental delay.
Microcephaly 2, primary, autosomal recessive, with or without cortical malformations
MedGen UID:
346929
Concept ID:
C1858535
Disease or Syndrome
In WDR62 primary microcephaly (WDR62-MCPH), microcephaly (occipitofrontal circumference [OFC] = -2 SD) is usually present at birth, but in some instances becomes evident later in the first year of life. Growth is otherwise normal. Except for brain malformations in most affected individuals, no other congenital malformations are observed. Central nervous system involvement can include delayed motor development, mild-to-severe intellectual disability (ID), behavior problems, epilepsy, spasticity, and ataxia.
Arthrogryposis, renal dysfunction, and cholestasis 1
MedGen UID:
347219
Concept ID:
C1859722
Disease or Syndrome
Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VPS33B gene.
Lissencephaly due to TUBA1A mutation
MedGen UID:
369910
Concept ID:
C1969029
Disease or Syndrome
Lissencephaly (LIS) due to TUBA1A mutation is a congenital cortical development anomaly due to abnormal neuronal migration involving neocortical and hippocampal lamination, corpus callosum, cerebellum and brainstem. A large clinical spectrum can be observed, from children with severe epilepsy and intellectual and motor deficit to cases with severe cerebral dysgenesis in the antenatal period leading to pregnancy termination due to the severity of the prognosis.
Lethal polymalformative syndrome, Boissel type
MedGen UID:
414158
Concept ID:
C2752001
Congenital Abnormality
Growth retardation, developmental delay, and facial dysmorphism (GDFD) is an autosomal recessive multiple congenital anomaly syndrome characterized by severe psychomotor retardation, poor overall growth, and dysmorphic facial features. Additional features may include cardiac malformations and deafness (summary by Daoud et al., 2016).
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5
MedGen UID:
461763
Concept ID:
C3150413
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of DAG1 (128239), collectively known as 'dystroglycanopathies' (Beltran-Valero de Bernabe et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Arthrogryposis, renal dysfunction, and cholestasis 2
MedGen UID:
462022
Concept ID:
C3150672
Disease or Syndrome
Arthrogryposis, renal dysfunction, and cholestasis-2 (ARCS2) is a multisystem disorder associated with abnormalities in polarized liver and kidney cells (Qiu et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of ARCS, see ARCS1 (208085).
Lissencephaly 4
MedGen UID:
462811
Concept ID:
C3151461
Disease or Syndrome
Lissencephaly-4 (LIS4) is an autosomal recessive neurodevelopmental disorder characterized by lissencephaly, severe brain atrophy, extreme microcephaly (head circumference of more than 10 standard deviations (SD) below the mean), and profound mental retardation. It has also been referred to as 'microlissencephaly' (summary by Bakircioglu et al., 2011 and Alkuraya et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Intellectual disability, autosomal recessive 34
MedGen UID:
482674
Concept ID:
C3281044
Disease or Syndrome
MRT34 is an autosomal recessive neurologic disorder characterized by mildly to moderately impaired intellectual development and megalencephaly or enlarged head circumference. Brain imaging shows a mild variant of lissencephaly with anterior-predominant pachygyria with shallow and unusually wide sulci and mildly thickened cortex. Some patients may have seizures (summary by Di Donato et al., 2016).
Baraitser-winter syndrome 2
MedGen UID:
482865
Concept ID:
C3281235
Disease or Syndrome
Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a multiple congenital anomaly syndrome characterized by typical craniofacial features and intellectual disability. Many (but not all) affected individuals have pachygyria that is predominantly frontal, wasting of the shoulder girdle muscles, and sensory impairment due to iris or retinal coloboma and/or sensorineural deafness. Intellectual disability, which is common but variable, is related to the severity of the brain malformations. Seizures, congenital heart defects, renal malformations, and gastrointestinal dysfunction are also common.
Complex cortical dysplasia with other brain malformations 7
MedGen UID:
765150
Concept ID:
C3552236
Disease or Syndrome
Complex cortical dysplasia with other brain malformations-7 is an autosomal dominant, clinically heterogeneous disorder showing a wide spectrum of abnormalities of cortical brain development. The most severely affected patients are fetuses with microlissencephaly, absence of the cortical plate, agenesis of the corpus callosum, and severely hypoplastic brainstem and cerebellum. Other patients have lissencephaly, polymicrogyria, cortical dysplasia, or neuronal heterotopia. Those with less severe malformations can survive, but usually have some degree of neurologic impairment, such as mental retardation, seizures, and movement abnormalities (summary by Chang et al., 2006; Fallet-Bianco et al., 2014). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039).
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 7
MedGen UID:
766244
Concept ID:
C3553330
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Roscioli et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Microcephalic primordial dwarfism due to RTTN deficiency
MedGen UID:
766745
Concept ID:
C3553831
Disease or Syndrome
A rare genetic neurodevelopmental disorder with primordial microcephaly, with characteristics of primary microcephaly, moderate to severe intellectual disability and global developmental delay. Variable brain malformations are common ranging from simplified gyration, to cortical malformations such as pachygyria, polymicrogyria, reduced sulcation and midline defects. Craniofacial dysmorphism (e.g. sloping forehead, high and broad nasal bridge) are related to the primary microcephaly. Short stature is frequently observed, and may be severe. Germline biallelic variants in RTTN (18q22.2) are responsible for the disease. The pattern of inheritance is autosomal recessive.
Peroxisome biogenesis disorder 11A (Zellweger)
MedGen UID:
766914
Concept ID:
C3554000
Disease or Syndrome
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 13 (CG13, equivalent to CGH) have mutations in the PEX13 gene. For information on the history of PBD complementation groups, see 214100.
Hydrocephalus, nonsyndromic, autosomal recessive 2
MedGen UID:
767605
Concept ID:
C3554691
Disease or Syndrome
Congenital hydrocephalus-2 is a congenital disorder with onset in utero. Affected individuals have hydrocephalus with variably dilated ventricles and variable neurologic sequelae. Some individuals have other brain abnormalities, including lissencephaly, thinning of the corpus callosum, and neuronal heterotopia. Most patients have delayed motor development and some have delayed intellectual development and/or seizures. Additional congenital features, including cardiac septal defects, iris coloboma, and nonspecific dysmorphic features, may be observed. Some patients die in utero, in infancy, or in early childhood, whereas others have long-term survival (summary by Shaheen et al., 2017). For a discussion of genetic heterogeneity of congenital hydrocephalus, see 233600.
Complex cortical dysplasia with other brain malformations 1
MedGen UID:
814727
Concept ID:
C3808397
Disease or Syndrome
Complex cortical dysplasia with other brain malformations (CDCBM) is a disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved (summary by Poirier et al., 2010). Mutation in the TUBB3 gene can also cause congenital fibrosis of extraocular muscles-3A (CFEOM3A; 600638), a milder and somewhat different neurologic phenotype. Genetic Heterogeneity of Complex Cortical Dysplasia With Other Brain Malformations See also CDCBM2 (615282), caused by mutation in the KIF5C gene (604593) on chromosome 2q23; CDCBM3 (615411), caused by mutation in the KIF2A gene (602591) on chromosome 5q12; CDCBM4 (615412), caused by mutation in the TUBG1 gene (191135) on chromosome 17q21; CDCBM5 (615763), caused by mutation in the TUBB2A gene (615101) on chromosome 6p25; CDCBM6 (615771), caused by mutation in the TUBB gene (191130) on chromosome 6p21; CDCBM7 (610031), caused by mutation in the TUBB2B gene (612850) on chromosome 6p25; CDCBM9 (618174), caused by mutation in the CTNNA2 gene (114025) on chromosome 2p12; and CDCBM10 (618677), caused by mutation in the APC2 gene (612034) on chromosome 19p13. The designation CDCBM8 was previously used to represent a phenotype caused by mutation in the TUBA8 gene (see 605742.0001) on chromosome 22q11; the patients with this phenotype were subsequently found to have a homozygous mutation in the SNAP29 gene (604202.0002), also on chromosome 22q11, that was likely responsible for a similar disorder, CEDNIK syndrome (609528). See also lissencephaly (e.g., LIS1, 607432), which shows overlapping features and may result from mutation in tubulin genes.
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12
MedGen UID:
815294
Concept ID:
C3808964
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with congenital muscular dystrophy resulting in muscle weakness early in life and brain and eye anomalies. It is usually associated with delayed psychomotor development and shortened life expectancy. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as dystroglycanopathies (summary by Stevens et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Complex cortical dysplasia with other brain malformations 3
MedGen UID:
815744
Concept ID:
C3809414
Disease or Syndrome
Any complex cortical dysplasia with other brain malformations in which the cause of the disease is a mutation in the KIF2A gene.
Neu-Laxova syndrome 2
MedGen UID:
863456
Concept ID:
C4015019
Disease or Syndrome
Neu-Laxova syndrome-2 is a rare autosomal recessive disorder characterized by a recognizable pattern of severe congenital malformations leading to prenatal or early postnatal lethality. Affected patients have abnormal craniofacial features, microcephaly, intrauterine growth retardation, ichthyosis, flexion deformities, limb malformations, and edema of the hands and feet. Some patients have malformations of the central nervous system, such as abnormal gyration (summary by Acuna-Hidalgo et al., 2014). For a discussion of genetic heterogeneity of Neu-Laxova syndrome, see NLS1 (256520).
Lissencephaly 6 with microcephaly
MedGen UID:
863962
Concept ID:
C4015525
Congenital Abnormality
Lissencephaly-6 (LIS6) is an autosomal recessive neurodevelopmental disorder characterized by severe microcephaly and developmental delay. Brain imaging shows variable malformations of cortical development, including lissencephaly, pachygyria, and hypoplasia of the corpus callosum (summary by Mishra-Gorur et al., 2014). For a general description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Lissencephaly 7 with cerebellar hypoplasia
MedGen UID:
895680
Concept ID:
C4225359
Disease or Syndrome
Lissencephaly-7 with cerebellar hypoplasia (LIS7) is a severe neurodevelopmental disorder characterized by lack of psychomotor development, facial dysmorphism, arthrogryposis, and early-onset intractable seizures resulting in death in infancy (Magen et al., 2015). For a general description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Galloway-Mowat syndrome 3
MedGen UID:
1627611
Concept ID:
C4540266
Disease or Syndrome
Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities of the brain, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Neu-Laxova syndrome 1
MedGen UID:
1633287
Concept ID:
C4551478
Disease or Syndrome
Any Neu-Laxova syndrome in which the cause of the disease is a mutation in the PHGDH gene.
Lissencephaly type 1 due to doublecortin gene mutation
MedGen UID:
1644310
Concept ID:
C4551968
Disease or Syndrome
DCX-related disorders include the neuronal migration disorders: Classic thick lissencephaly (more severe anteriorly), usually in males. Subcortical band heterotopia (SBH), primarily in females. Males with classic DCX-related lissencephaly typically have early and profound cognitive and language impairment, cerebral palsy, and epileptic seizures. The clinical phenotype in females with SBH varies widely with cognitive abilities that range from average or mild cognitive impairment to severe intellectual disability and language impairment. Seizures, which frequently are refractory to anti-seizure medication, may be either focal or generalized and behavioral problems may also be observed. In DCX-related lissencephaly and SBH the severity of the clinical manifestation correlates roughly with the degree of the underlying brain malformation as observed in cerebral imaging.
Pseudo-TORCH syndrome 1
MedGen UID:
1639355
Concept ID:
C4552078
Disease or Syndrome
Alkuraya-Kucinskas syndrome
MedGen UID:
1634304
Concept ID:
C4693347
Disease or Syndrome
ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures (summary by Gueneau et al., 2018).
Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome
MedGen UID:
1648412
Concept ID:
C4748348
Disease or Syndrome
MFRG is an autosomal recessive syndrome in which microcephaly, unilateral renal agenesis, ambiguous genitalia, and facial dysmorphisms, including severe micrognathia, are observed in most patients. Variable brain, cardiac, and skeletal anomalies are present, including corpus callosum agenesis or dysgenesis, lissencephaly, atrial and ventricular septal defects, patent ductus arteriosus, hypoplastic right ventricle, and joint contractures (Shaheen et al., 2016).
Lissencephaly due to LIS1 mutation
MedGen UID:
1657090
Concept ID:
C4749301
Congenital Abnormality
PAFAH1B1-related lissencephaly/subcortical band heterotopia (SBH) comprises a spectrum of severity. Affected newborns typically have mild-to-moderate hypotonia, feeding difficulties, and poor head control. During the first years, neurologic examination typically demonstrates poor visual tracking and response to sounds, axial hypotonia, and mild distal spasticity that can transition over time to more severe spasticity. Seizures occur in more than 90% of individuals with lissencephaly and often include infantile spasms. Seizures are often drug resistant, but even with good seizure control, the best developmental level achieved (excluding the few individuals with partial lissencephaly) is the equivalent of about age three to five months. In individuals with PAFAH1B1-related lissencephaly/SBH, developmental delay ranges from mild to severe. Other findings in PAFAH1B1-related lissencephaly/SBH include feeding issues and aspiration (which may result in need for gastrostomy tube placement), progressive microcephaly, and occasional developmental regression.
Lissencephaly 9 with complex brainstem malformation
MedGen UID:
1681109
Concept ID:
C5193029
Disease or Syndrome
Lissencephaly-9 with complex brainstem malformation (LIS9) is an autosomal dominant neurologic disorder characterized by global developmental delay apparent since infancy, impaired intellectual development with poor or absent speech, and sometimes abnormal or involuntary movements associated with abnormal brain imaging that typically shows pachygyria, lissencephaly, and malformation of the brainstem consistent with a neuronal migration defect (summary by Dobyns et al., 2018). For a general description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Cortical dysplasia, complex, with other brain malformations 10
MedGen UID:
1684859
Concept ID:
C5231458
Disease or Syndrome
Complex cortical dysplasia with other brain malformations-10 (CDCBM10) is an autosomal recessive neurodevelopmental disorder characterized by severely impaired global development associated with abnormalities on brain imaging, including lissencephaly, cortical dysplasia, subcortical heterotopia, and paucity of white matter. The disorder results from defective neuronal migration during brain development. Affected individuals often develop seizures, are unable to walk, and do not acquire language (summary by Lee et al., 2019). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039).
Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity
MedGen UID:
1684695
Concept ID:
C5231480
Disease or Syndrome
Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity (NEDMCMS) is an autosomal recessive disorder characterized by severe to profound global developmental delay, early-onset seizures, microcephaly, and polymicrogyria and/or cerebral atrophy on brain imaging. Most affected individuals are unable to walk or speak and have profoundly impaired intellectual development, as well as axial hypotonia and peripheral spasticity. Rare individuals may be less severely affected (summary by Vandervore et al., 2019).
Ciliary dyskinesia, primary, 47, and lissencephaly
MedGen UID:
1794161
Concept ID:
C5561951
Disease or Syndrome
Primary ciliary dyskinesia-47 and lissencephaly (CILD47) is an autosomal recessive disorder characterized by onset of recurrent respiratory infections and respiratory dysfunction caused by defective mucociliary clearance in early childhood. Affected individuals also have neurologic features, such as impaired intellectual development and central hypotonia, associated with structural brain abnormalities, most notably lissencephaly and thin or absent corpus callosum. The disorder results from impaired function of motile ciliopathy and can be classified as 'reduced generation of multiple motile cilia' (RGMC). Situs inversus is not observed (summary by Wallmeier et al., 2021). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly
MedGen UID:
1808159
Concept ID:
C5676961
Disease or Syndrome
Autosomal recessive intellectual developmental disorder-75 with neuropsychiatric features and variant lissencephaly (MRT75) is characterized by global developmental delay apparent from infancy or early childhood and moderate to profoundly impaired intellectual development. Most affected individuals have behavioral abnormalities, including aggression and ADHD; a few have psychiatric manifestations, including psychosis. More variable additional features include well-controlled seizures and dysmorphic facial features. Brain imaging often shows frontal predominant pachygyria or other gyri/sulci abnormalities, consistent with a variant of lissencephaly and a malformation of cortical development (MCD) (summary by Zaki et al., 2021).

Recent clinical studies

Etiology

Zhang YL, Jing XY, Zhen L, Pan M, Han J, Li DZ
Eur J Obstet Gynecol Reprod Biol 2022 Jul;274:28-32. Epub 2022 May 6 doi: 10.1016/j.ejogrb.2022.04.025. PMID: 35567955
Contrò G, Micalizzi A, Giangiobbe S, Caraffi SG, Zuntini R, Rosato S, Pollazzon M, Terracciano A, Napoli M, Rizzi S, Salerno GG, Radio FC, Niceta M, Parrini E, Fusco C, Gargano G, Guerrini R, Tartaglia M, Novelli A, Zuffardi O, Garavelli L
Genes (Basel) 2021 Aug 5;12(8) doi: 10.3390/genes12081208. PMID: 34440382Free PMC Article
Kolbjer S, Martin DA, Pettersson M, Dahlin M, Anderlid BM
Eur J Paediatr Neurol 2021 Jan;30:71-81. Epub 2021 Jan 8 doi: 10.1016/j.ejpn.2020.12.011. PMID: 33453472
Jauhari P, Farmania R, Chakrabarty B, Kumar A, Gulati S
Seizure 2020 Dec;83:175-180. Epub 2020 Oct 31 doi: 10.1016/j.seizure.2020.10.020. PMID: 33161247
Arrigoni F, Peruzzo D, Mandelstam S, Amorosino G, Redaelli D, Romaniello R, Leventer R, Borgatti R, Seal M, Yang JY
AJNR Am J Neuroradiol 2020 Aug;41(8):1495-1502. Epub 2020 Jul 30 doi: 10.3174/ajnr.A6646. PMID: 32732266Free PMC Article

Diagnosis

Zhang YL, Jing XY, Zhen L, Pan M, Han J, Li DZ
Eur J Obstet Gynecol Reprod Biol 2022 Jul;274:28-32. Epub 2022 May 6 doi: 10.1016/j.ejogrb.2022.04.025. PMID: 35567955
Koenig M, Dobyns WB, Di Donato N
Eur J Paediatr Neurol 2021 Nov;35:147-152. Epub 2021 Oct 7 doi: 10.1016/j.ejpn.2021.09.013. PMID: 34731701
Contrò G, Micalizzi A, Giangiobbe S, Caraffi SG, Zuntini R, Rosato S, Pollazzon M, Terracciano A, Napoli M, Rizzi S, Salerno GG, Radio FC, Niceta M, Parrini E, Fusco C, Gargano G, Guerrini R, Tartaglia M, Novelli A, Zuffardi O, Garavelli L
Genes (Basel) 2021 Aug 5;12(8) doi: 10.3390/genes12081208. PMID: 34440382Free PMC Article
Jauhari P, Farmania R, Chakrabarty B, Kumar A, Gulati S
Seizure 2020 Dec;83:175-180. Epub 2020 Oct 31 doi: 10.1016/j.seizure.2020.10.020. PMID: 33161247
Arrigoni F, Peruzzo D, Mandelstam S, Amorosino G, Redaelli D, Romaniello R, Leventer R, Borgatti R, Seal M, Yang JY
AJNR Am J Neuroradiol 2020 Aug;41(8):1495-1502. Epub 2020 Jul 30 doi: 10.3174/ajnr.A6646. PMID: 32732266Free PMC Article

Therapy

Kolbjer S, Martin DA, Pettersson M, Dahlin M, Anderlid BM
Eur J Paediatr Neurol 2021 Jan;30:71-81. Epub 2021 Jan 8 doi: 10.1016/j.ejpn.2020.12.011. PMID: 33453472
Herbst SM, Proepper CR, Geis T, Borggraefe I, Hahn A, Debus O, Haeussler M, von Gersdorff G, Kurlemann G, Ensslen M, Beaud N, Budde J, Gilbert M, Heiming R, Morgner R, Philippi H, Ross S, Strobl-Wildemann G, Muelleder K, Vosschulte P, Morris-Rosendahl DJ, Schuierer G, Hehr U
Brain Dev 2016 Apr;38(4):399-406. Epub 2015 Oct 19 doi: 10.1016/j.braindev.2015.10.001. PMID: 26494205
Kumar S, Suthar R, Panigrahi I, Marwaha RK
J Pediatr Endocrinol Metab 2013;26(11-12):1175-7. doi: 10.1515/jpem-2013-0102. PMID: 23751382
Toba S, Tamura Y, Kumamoto K, Yamada M, Takao K, Hattori S, Miyakawa T, Kataoka Y, Azuma M, Hayasaka K, Amamoto M, Tominaga K, Wynshaw-Boris A, Wanibuchi H, Oka Y, Sato M, Kato M, Hirotsune S
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Ozdemir H, Aycan Z, Degerliyurt A, Metin A
Turk Neurosurg 2010 Jan;20(1):100-2. PMID: 20066633

Prognosis

Lo HY, Ng WF, Fong NC, Lui CD, Lam CW
Am J Med Genet A 2022 Jul;188(7):2168-2172. Epub 2022 Mar 22 doi: 10.1002/ajmg.a.62732. PMID: 35316582
Kolbjer S, Martin DA, Pettersson M, Dahlin M, Anderlid BM
Eur J Paediatr Neurol 2021 Jan;30:71-81. Epub 2021 Jan 8 doi: 10.1016/j.ejpn.2020.12.011. PMID: 33453472
Jauhari P, Farmania R, Chakrabarty B, Kumar A, Gulati S
Seizure 2020 Dec;83:175-180. Epub 2020 Oct 31 doi: 10.1016/j.seizure.2020.10.020. PMID: 33161247
Harel T, Hacohen N, Shaag A, Gomori M, Singer A, Elpeleg O, Meiner V
Am J Med Genet A 2017 Sep;173(9):2539-2544. Epub 2017 Jul 7 doi: 10.1002/ajmg.a.38347. PMID: 28686357
Di Donato N, Chiari S, Mirzaa GM, Aldinger K, Parrini E, Olds C, Barkovich AJ, Guerrini R, Dobyns WB
Am J Med Genet A 2017 Jun;173(6):1473-1488. Epub 2017 Apr 25 doi: 10.1002/ajmg.a.38245. PMID: 28440899Free PMC Article

Clinical prediction guides

Simoes C, Graña M, Rodriguez S, Baltar Yanes F, Tapié A, Dell'Oca N, Naya H, Raggio V, Spangenberg L
BMC Pediatr 2022 Sep 14;22(1):545. doi: 10.1186/s12887-022-03595-6. PMID: 36100855Free PMC Article
Kolbjer S, Martin DA, Pettersson M, Dahlin M, Anderlid BM
Eur J Paediatr Neurol 2021 Jan;30:71-81. Epub 2021 Jan 8 doi: 10.1016/j.ejpn.2020.12.011. PMID: 33453472
Jauhari P, Farmania R, Chakrabarty B, Kumar A, Gulati S
Seizure 2020 Dec;83:175-180. Epub 2020 Oct 31 doi: 10.1016/j.seizure.2020.10.020. PMID: 33161247
Markus SM, Marzo MG, McKenney RJ
Elife 2020 Jul 21;9 doi: 10.7554/eLife.59737. PMID: 32692650Free PMC Article
Williams F, Griffiths PD
Br J Radiol 2017 Apr;90(1072):20160902. Epub 2017 Mar 3 doi: 10.1259/bjr.20160902. PMID: 28134568Free PMC Article

Recent systematic reviews

Brock S, Cools F, Jansen AC
Neuropathol Appl Neurobiol 2021 Aug;47(5):585-602. Epub 2021 Feb 14 doi: 10.1111/nan.12696. PMID: 33480109Free PMC Article

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