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Gray matter heterotopia

MedGen UID:
452349
Concept ID:
C0266491
Disease or Syndrome; Finding; Finding
Synonym: Gray matter heterotopias
SNOMED CT: Cortical heterotopia (448041008); Neuronal heterotopia (448041008); Neuronal heterotopia (253150002); Gray matter heterotopia (448041008)
 
HPO: HP:0002282

Definition

Heterotopia or neuronal heterotopia are macroscopic clusters of misplaced neurons (gray matter), most often situated along the ventricular walls or within the subcortical white matter. [from HPO]

Conditions with this feature

Ito hypomelanosis
MedGen UID:
5920
Concept ID:
C0022283
Congenital Abnormality
A large brown, blue, or gray hamartoma of dermal melanocytes, usually on the shoulder and upper arm that is most commonly found in Asian populations and in females. It is sometimes associated with sensory changes in the involved skin area, but very rarely becomes cancerous.
Aicardi syndrome
MedGen UID:
61236
Concept ID:
C0175713
Disease or Syndrome
Aicardi syndrome is a neurodevelopmental disorder that affects primarily females. Initially it was characterized by a typical triad of agenesis of the corpus callosum, central chorioretinal lacunae, and infantile spasms. As more affected individuals have been ascertained, it has become clear that not all affected girls have all three features of the classic triad and that other neurologic and systemic defects are common, including other brain malformations, optic nerve abnormalities, other seizure types, intellectual disability of varying severity, and scoliosis.
FG syndrome
MedGen UID:
113106
Concept ID:
C0220769
Disease or Syndrome
Opitz-Kaveggia syndrome (OKS) is an X-linked recessive mental retardation syndrome characterized by dysmorphic features, including relative macrocephaly, hypertelorism, downslanted palpebral fissures, prominent forehead with frontal hair upsweep, and broad thumbs and halluces. Most have hypotonia, constipation, and partial agenesis of the corpus callosum. Some patients have sensorineural hearing loss and joint laxity evolving into joint contractures. Affected individuals tend to be hyperactive and talkative (summary by Graham et al., 1999). In their original family, Opitz and Kaveggia (1974) named the disorder 'FG syndrome' according to the Opitz system of using initials of patients' surnames. Genetic Heterogeneity of FG Syndrome Other forms of 'FG syndrome' were characterized due to the similar clinical features observed by Opitz and Kaveggia (1974). FGS2 (300321) is caused by mutation in the FLNA gene (300017) on chromosome Xq28 and FGS4 (300422) is caused by mutation in the CASK gene (300172) on chromosome Xp11. FGS3 (300406) has been mapped to Xp22.3, and FGS5 (300581) to Xq22.3. Risheg et al. (2007) suggested that the designation Opitz-Kaveggia syndrome be reserved for those cases with mutation in the MED12 gene. In part this is justified by the fact that a MED12 mutation was found in the family originally reported by Opitz and Kaveggia (1974).
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.
Chiari malformation type II
MedGen UID:
108222
Concept ID:
C0555206
Congenital Abnormality
Chiari malformation type II (CM2), also known as the Arnold-Chiari malformation, consists of elongation and descent of the inferior cerebellar vermis, cerebellar hemispheres, pons, medulla, and fourth ventricle through the foramen magnum into the spinal canal. CM2 is uniquely associated with myelomeningocele (open spina bifida; see 182940) and is found only in this population (Stevenson, 2004). It is believed to be a disorder of neuroectodermal origin (Schijman, 2004). For a general phenotypic description of the different forms of Chiari malformations, see Chiari malformation type I (CM1; 118420).
Oculocerebrocutaneous syndrome
MedGen UID:
163214
Concept ID:
C0796092
Disease or Syndrome
A rare neurologic disease typically characterized by the triad of eye, central nervous system and skin malformations, and often associated with an intellectual disability.
Bohring-Opitz syndrome
MedGen UID:
208678
Concept ID:
C0796232
Disease or Syndrome
Bohring-Opitz syndrome (BOS) is characterized by distinctive facial features and posture, growth failure, variable but usually severe intellectual disability, and variable anomalies. The facial features may include microcephaly or trigonocephaly / prominent (but not fused) metopic ridge, hypotonic facies with full cheeks, synophrys, glabellar and eyelid nevus flammeus (simplex), prominent globes, widely set eyes, palate anomalies, and micrognathia. The BOS posture, which is most striking in early childhood and often becomes less apparent with age, is characterized by flexion at the elbows with ulnar deviation and flexion of the wrists and metacarpophalangeal joints. Feeding difficulties in early childhood, including cyclic vomiting, have a significant impact on overall health; feeding tends to improve with age. Seizures are common and typically responsive to standard epileptic medications. Minor cardiac anomalies and transient bradycardia and apnea may be present. Affected individuals may experience recurrent infections, which also tend to improve with age. Isolated case reports suggest that individuals with BOS are at greater risk for Wilms tumor than the general population, but large-scale epidemiologic studies have not been conducted.
Orofaciodigital syndrome I
MedGen UID:
307142
Concept ID:
C1510460
Disease or Syndrome
Oral-facial-digital syndrome type I (OFD1) is usually male lethal during gestation and predominantly affects females. OFD1 is characterized by the following features: Oral (lobulated tongue, tongue nodules, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities). Facial (widely spaced eyes or telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft upper lip, micrognathia). Digital (brachydactyly, syndactyly, clinodactyly of the fifth finger; duplicated hallux [great toe]). Kidney (polycystic kidney disease). Brain (e.g., intracerebral cysts, agenesis of the corpus callosum, cerebellar agenesis with or without Dandy-Walker malformation). Intellectual disability (in ~50% of individuals).
Midface hypoplasia, obesity, developmental delay, and neonatal hypotonia
MedGen UID:
325238
Concept ID:
C1837730
Disease or Syndrome
Heterotopia, periventricular, X-linked dominant
MedGen UID:
376309
Concept ID:
C1848213
Disease or Syndrome
FLNA deficiency is associated with a phenotypic spectrum that includes FLNA-related periventricular nodular heterotopia (Huttenlocher syndrome), congenital heart disease (patent ductus arteriosus, atrial and ventricular septal defects), valvular dystrophy, dilation and rupture of the thoracic aortic, pulmonary disease (pulmonary hypertension, alveolar hypoplasia, emphysema, asthma, chronic bronchitis), gastrointestinal dysmotility and obstruction, joint hypermobility, and macrothrombocytopenia.
Joubert syndrome with oculorenal defect
MedGen UID:
340930
Concept ID:
C1855675
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Vici syndrome
MedGen UID:
340962
Concept ID:
C1855772
Disease or Syndrome
With the current widespread use of multigene panels and comprehensive genomic testing, it has become apparent that the phenotypic spectrum of EPG5-related disorder represents a continuum. At the most severe end of the spectrum is classic Vici syndrome (defined as a neurodevelopmental disorder with multisystem involvement characterized by the combination of agenesis of the corpus callosum, cataracts, hypopigmentation, cardiomyopathy, combined immunodeficiency, microcephaly, and failure to thrive); at the milder end of the spectrum are attenuated neurodevelopmental phenotypes with variable multisystem involvement. Median survival in classic Vici syndrome appears to be 24 months, with only 10% of children surviving longer than age five years; the most common causes of death are respiratory infections as a result of primary immunodeficiency and/or cardiac insufficiency resulting from progressive cardiac failure. No data are available on life span in individuals at the milder end of the spectrum.
Hydrolethalus syndrome 1
MedGen UID:
343455
Concept ID:
C1856016
Disease or Syndrome
Any hydrolethalus syndrome in which the cause of the disease is a mutation in the HYLS1 gene.
Ventriculomegaly-cystic kidney disease
MedGen UID:
346584
Concept ID:
C1857423
Disease or Syndrome
Ventriculomegaly with cystic kidney disease is a severe autosomal recessive developmental disorder characterized by onset in utero of dilated cerebral ventricles and microscopic renal tubular cysts. The pregnancies of affected individuals are associated with increased alpha-fetoprotein (AFP). Most affected pregnancies have been terminated (summary by Slavotinek et al., 2015). See also 602200 for a disorder characterized by ventriculomegaly and defects of the radius and kidney.
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.
Chudley-McCullough syndrome
MedGen UID:
347699
Concept ID:
C1858695
Disease or Syndrome
Chudley-McCullough syndrome is an autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal (summary by Alrashdi et al., 2011).
Osteodysplastic primordial dwarfism, type 1
MedGen UID:
347149
Concept ID:
C1859452
Congenital Abnormality
Microcephalic osteodysplastic primordial dwarfism type I is a severe autosomal recessive skeletal dysplasia characterized by dwarfism, microcephaly, and neurologic abnormalities, including mental retardation, brain malformations, and ocular/auditory sensory deficits. Patients often die in early childhood (summary by Pierce and Morse, 2012).
Acromelic frontonasal dysostosis
MedGen UID:
350933
Concept ID:
C1863616
Disease or Syndrome
Verloes et al. (1992) described a rare variant of frontonasal dysplasia (see FND1, 136760), designated acromelic frontonasal dysplasia (AFND), in which similar craniofacial anomalies are associated with variable central nervous system malformations and limb defects including tibial hypoplasia/aplasia, talipes equinovarus, and preaxial polydactyly of the feet.
Koolen-de Vries syndrome
MedGen UID:
355853
Concept ID:
C1864871
Disease or Syndrome
Koolen-de Vries syndrome (KdVS) is characterized by developmental delay / intellectual disability, neonatal/childhood hypotonia, dysmorphisms, congenital malformations, and behavioral features. Psychomotor developmental delay is noted in all individuals from an early age. The majority of individuals with KdVS function in the mild-to-moderate range of intellectual disability. Other findings include speech and language delay (100%), epilepsy (~33%), congenital heart defects (25%-50%), renal and urologic anomalies (25%-50%), and cryptorchidism (71% of males). Behavior in most is described as friendly, amiable, and cooperative.
Thanatophoric dysplasia type 1
MedGen UID:
358383
Concept ID:
C1868678
Disease or Syndrome
Thanatophoric dysplasia (TD) is a short-limb skeletal dysplasia that is usually lethal in the perinatal period. TD is divided into subtypes: TD type I is characterized by micromelia with bowed femurs and, uncommonly, the presence of craniosynostosis of varying severity. TD type II is characterized by micromelia with straight femurs and uniform presence of moderate-to-severe craniosynostosis with cloverleaf skull deformity. Other features common to type I and type II include: short ribs, narrow thorax, relative macrocephaly, distinctive facial features, brachydactyly, hypotonia, and redundant skin folds along the limbs. Most affected infants die of respiratory insufficiency shortly after birth. Rare long-term survivors have been reported.
Lissencephaly type 3
MedGen UID:
369910
Concept ID:
C1969029
Disease or Syndrome
An autosomal dominant sub-type of lissencephaly caused by mutation(s) in the TUBA1A gene, encoding adhesion tubulin alpha-1A chain.
Fontaine progeroid syndrome
MedGen UID:
394125
Concept ID:
C2676780
Disease or Syndrome
SLC25A24 Fontaine progeroid syndrome is a multisystem connective tissue disorder characterized by poor growth, abnormal skeletal features, and distinctive craniofacial features with sagging, thin skin, and decreased subcutaneous fat suggesting an aged appearance that is most pronounced in infancy and improves with time. Characteristic radiographic features include turribrachycephaly with widely open anterior fontanelle, craniosynostosis, and anomalies of the terminal phalanges. Cardiovascular, genitourinary, ocular, and gastrointestinal abnormalities may also occur. To date, 13 individuals with a molecularly confirmed diagnosis of SLC25A24 Fontaine progeroid syndrome have been described.
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).
Cobblestone lissencephaly without muscular or ocular involvement
MedGen UID:
767571
Concept ID:
C3554657
Disease or Syndrome
Lissencephaly-5 (LIS5) is an autosomal recessive brain malformation characterized by cobblestone changes in the cortex, more severe in the posterior region, and subcortical band heterotopia. Affected individuals have hydrocephalus, seizures, and severely delayed psychomotor development (Radmanesh et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Hydrocephalus, nonsyndromic, autosomal recessive 2
MedGen UID:
767605
Concept ID:
C3554691
Disease or Syndrome
Congenital hydrocephalus-2 (HYC2) 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.
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13
MedGen UID:
815372
Concept ID:
C3809042
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is a autosomal recessive disorder associated with severe neurologic defects and resulting in early infantile death. 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 Buysse 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.
Periventricular nodular heterotopia 6
MedGen UID:
816202
Concept ID:
C3809872
Disease or Syndrome
Any periventricular nodular heterotopia in which the cause of the disease is a mutation in the ERMARD gene.
Van Maldergem syndrome 2
MedGen UID:
816205
Concept ID:
C3809875
Disease or Syndrome
Van Maldergem syndrome is an autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia (summary by Cappello et al., 2013). For a discussion of genetic heterogeneity of Van Maldergem syndrome, see 601390.
Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome
MedGen UID:
863258
Concept ID:
C4014821
Disease or Syndrome
Poretti-Boltshauser syndrome is an autosomal recessive disorder characterized by cerebellar dysplasia, cerebellar vermis hypoplasia, cerebellar cysts in most patients, high myopia, variable retinal dystrophy, and eye movement abnormalities. Affected individuals have delayed motor development and often have speech delay. Cognitive function can range from normal to intellectually disabled (summary by Aldinger et al., 2014).
Band heterotopia of brain
MedGen UID:
924885
Concept ID:
C4284594
Disease or Syndrome
Periventricular nodular heterotopia 7
MedGen UID:
934636
Concept ID:
C4310669
Disease or Syndrome
Periventricular nodular heterotopia-7 (PVNH7) is a neurologic disorder characterized by abnormal neuronal migration during brain development resulting in delayed psychomotor development and intellectual disability; some patients develop seizures. Other features include cleft palate and 2-3 toe syndactyly (summary by Broix et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of periventricular heterotopia, see 300049.
Cerebral palsy, spastic quadriplegic, 3
MedGen UID:
934734
Concept ID:
C4310767
Disease or Syndrome
Any spastic quadriplegia in which the cause of the disease is a mutation in the ADD3 gene.
Pseudo-TORCH syndrome 2
MedGen UID:
1373355
Concept ID:
C4479376
Disease or Syndrome
Pseudo-TORCH syndrome-2 (PTORCH2) is an autosomal recessive multisystem disorder characterized by antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent. The disorder results from inappropriate activation of the interferon (IFN) immunologic pathway (summary by Meuwissen et al., 2016). For a discussion of genetic heterogeneity of PTORCH, see PTORCH1 (251290).
Orofaciodigital syndrome 16
MedGen UID:
1620071
Concept ID:
C4539729
Disease or Syndrome
Joubert syndrome 30
MedGen UID:
1613861
Concept ID:
C4539937
Disease or Syndrome
Van Maldergem syndrome 1
MedGen UID:
1644627
Concept ID:
C4551950
Disease or Syndrome
Van Maldergem syndrome is an autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia (summary by Cappello et al., 2013). Genetic Heterogeneity of Van Maldergem Syndrome See also VMLDS2 (615546), caused by mutation in the FAT4 gene (612411) on chromosome 4q28.
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.
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).
Peroxisome biogenesis disorder 1A (Zellweger)
MedGen UID:
1648474
Concept ID:
C4721541
Disease or Syndrome
Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal adrenoleukodystrophy [NALD], and infantile Refsum disease [IRD]) were described in the past before the biochemical and molecular bases of this spectrum were fully determined, the term "ZSD" is now used to refer to all individuals with a defect in one of the ZSD-PEX genes regardless of phenotype. Individuals with ZSD usually come to clinical attention in the newborn period or later in childhood. Affected newborns are hypotonic and feed poorly. They have distinctive facies, congenital malformations (neuronal migration defects associated with neonatal-onset seizures, renal cysts, and bony stippling [chondrodysplasia punctata] of the patella[e] and the long bones), and liver disease that can be severe. Infants with severe ZSD are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Individuals with intermediate/milder ZSD do not have congenital malformations, but rather progressive peroxisome dysfunction variably manifest as sensory loss (secondary to retinal dystrophy and sensorineural hearing loss), neurologic involvement (ataxia, polyneuropathy, and leukodystrophy), liver dysfunction, adrenal insufficiency, and renal oxalate stones. While hypotonia and developmental delays are typical, intellect can be normal. Some have osteopenia; almost all have ameleogenesis imperfecta in the secondary teeth.
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.
Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation
MedGen UID:
1716098
Concept ID:
C5394091
Disease or Syndrome
Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation (NEDHRIT) is a severe autosomal recessive disorder characterized by neonatal respiratory distress, poor feeding, and impaired global development. Affected individuals are unable to walk or speak and have poor or absent eye contact. Some patients may develop seizures (summary by Wagner et al., 2020).
Genitourinary and/or brain malformation syndrome
MedGen UID:
1720440
Concept ID:
C5394158
Disease or Syndrome
Individuals with PPP1R12A-related urogenital and/or brain malformation syndrome (UBMS) usually present with multiple congenital anomalies, commonly including brain and/or urogenital malformations. The brain abnormalities are variable, with the most severe belonging to the holoprosencephaly spectrum and associated with moderate-to-profound intellectual disability, seizures, and feeding difficulties. In individuals without brain involvement, variable degrees of developmental delay and/or intellectual disability may be present, although normal intelligence has been seen in a minority of affected individuals. Eye abnormalities and skeletal issues (kyphoscoliosis, joint contractures) can also be present in individuals of either sex. Regardless of the presence of a brain malformation, affected individuals with a 46,XY chromosome complement may have a disorder of sex development (DSD) with gonadal abnormalities (dysgenetic gonads or streak gonads). Individuals with a 46,XX chromosome complement may have varying degrees of virilization (clitoral hypertrophy, posterior labial fusion, urogenital sinus).
Periventricular nodular heterotopia 9
MedGen UID:
1718470
Concept ID:
C5394503
Disease or Syndrome
Periventricular nodular heterotopia-9 (PVNH9) is an autosomal dominant neurologic disorder characterized as a malformation of cortical development. Anterior predominant PVNH, thin corpus callosum, and decreased white matter volume are found on brain imaging, but the clinical effects are variable. Most patients have impaired intellectual development and cognitive defects associated with low IQ (range 50 to 80), learning disabilities, and behavior abnormalities. Some patients develop seizures that tend to have a focal origin. However, some mutation carriers may be less severely affected with borderline or even normal IQ, suggesting incomplete penetrance of the phenotype (summary by Heinzen et al., 2018, Walters et al., 2018). For a discussion of genetic heterogeneity of periventricular nodular heterotopia, see 300049.
Turcot syndrome
MedGen UID:
1748029
Concept ID:
C5399763
Disease or Syndrome
Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, ovary, stomach, small bowel, urinary tract, biliary tract, brain (usually glioblastoma), skin (sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas), pancreas, and prostate. Cancer risks and age of onset vary depending on the associated gene. Several other cancer types have been reported to occur in individuals with Lynch syndrome (e.g., breast, sarcomas, adrenocortical carcinoma). However, the data are not sufficient to demonstrate that the risk of developing these cancers is increased in individuals with Lynch syndrome.
Mismatch repair cancer syndrome 4
MedGen UID:
1745382
Concept ID:
C5436817
Disease or Syndrome
Mismatch repair cancer syndrome-4 (MMRCS4) is an autosomal recessive childhood cancer predisposition syndrome characterized by early-onset leukemia/lymphoma, brain tumors, colorectal/gastrointestinal cancers, and other rare malignancies, including rhabdomyosarcoma (summary by Li et al., 2015). Cafe-au-lait spots are usually present (De Vos et al., 2006). For a discussion of genetic heterogeneity of mismatch repair cancer syndrome, see MMRCS1 (276300).
Radio-Tartaglia syndrome
MedGen UID:
1778557
Concept ID:
C5543339
Disease or Syndrome
Radio-Tartaglia syndrome (RATARS) is a neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development, speech delay, and variable behavioral abnormalities. Affected individuals show hypotonia, mild motor difficulties, and craniofacial dysmorphism. Brain imaging may show nonspecific defects; rare patients have seizures or pyramidal signs. A subset of individuals may have congenital heart defects, precocious puberty, and obesity in females. Some of the features are similar to those observed in patients with chromosome 1p36 deletion syndrome (607872) (summary by Radio et al., 2021).
Developmental delay with variable neurologic and brain abnormalities
MedGen UID:
1794270
Concept ID:
C5562060
Disease or Syndrome
Developmental delay with variable neurologic and brain abnormalities (DENBA) is characterized most often by motor and speech delay apparent from early childhood. Most patients have delayed walking and variably impaired intellectual development. Additional neurologic features may include seizures, spasticity, and ocular abnormalities. Brain imaging often shows thin corpus callosum and may show white matter atrophy, myelination abnormalities, or enlarged ventricles. The severity of the disorder and clinical manifestations are highly variable (summary by Malhotra et al., 2021).
Congenital disorder of deglycosylation 2
MedGen UID:
1809253
Concept ID:
C5676931
Disease or Syndrome
Congenital disorder of deglycosylation-2 (CDDG2) is an autosomal recessive disorder with variable associated features such as dysmorphic facies, impaired intellectual development, and brain anomalies, including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis (Maia et al., 2022). For a discussion of genetic heterogeneity of congenital disorder of deglycosylation, see CDGG1 (615273).
Holoprosencephaly 14
MedGen UID:
1811868
Concept ID:
C5676994
Disease or Syndrome
Holoprosencephaly-14 (HPE14) is an autosomal recessive condition characterized by severe developmental delay secondary to brain malformations within the holoprosencephaly spectrum (Drissi et al., 2022). For general phenotypic information and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100).

Recent clinical studies

Etiology

Di Nora A, Costanza G, Pizzo F, Oliva CF, Di Mari A, Greco F, Pavone P
Acta Neurol Belg 2022 Feb;122(1):153-162. Epub 2021 Sep 1 doi: 10.1007/s13760-021-01774-3. PMID: 34471972Free PMC Article
Neuhaus E, Hattingen E, Breuer S, Steidl E, Polomac N, Rosenow F, Rüber T, Herrmann E, Ecker C, Kushan L, Lin A, Vajdi A, Bearden CE, Jurcoane A
AJNR Am J Neuroradiol 2021 Nov;42(11):2070-2076. Epub 2021 Oct 7 doi: 10.3174/ajnr.A7283. PMID: 34620586Free PMC Article
Oegema R, McGillivray G, Leventer R, Le Moing AG, Bahi-Buisson N, Barnicoat A, Mandelstam S, Francis D, Francis F, Mancini GMS, Savelberg S, van Haaften G, Mankad K, Lequin MH
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):627-637. Epub 2019 Nov 11 doi: 10.1002/ajmg.c.31751. PMID: 31710781Free PMC Article
Raza HK, Chen H, Chansysouphanthong T, Zhang Z, Hua F, Ye X, Zhang W, Dong L, Zhang S, Wang X, Cui G
Neurol Sci 2019 Mar;40(3):489-494. Epub 2018 Dec 10 doi: 10.1007/s10072-018-3667-9. PMID: 30535564
Barkovich AJ, Kuzniecky RI
Neurology 2000 Dec 12;55(11):1603-8. doi: 10.1212/wnl.55.11.1603. PMID: 11187088

Diagnosis

Di Nora A, Costanza G, Pizzo F, Oliva CF, Di Mari A, Greco F, Pavone P
Acta Neurol Belg 2022 Feb;122(1):153-162. Epub 2021 Sep 1 doi: 10.1007/s13760-021-01774-3. PMID: 34471972Free PMC Article
Raza HK, Chen H, Chansysouphanthong T, Zhang Z, Hua F, Ye X, Zhang W, Dong L, Zhang S, Wang X, Cui G
Neurol Sci 2019 Mar;40(3):489-494. Epub 2018 Dec 10 doi: 10.1007/s10072-018-3667-9. PMID: 30535564
Yang E, Chu WCW, Lee EY
Radiol Clin North Am 2017 Jul;55(4):609-627. doi: 10.1016/j.rcl.2017.02.005. PMID: 28601171
Gao Z, Massimi L, Rogerio S, Raybaud C, Di Rocco C
Childs Nerv Syst 2014 Jan;30(1):65-72. Epub 2013 Aug 29 doi: 10.1007/s00381-013-2249-7. PMID: 23989428
Christodoulou JA, Walker LM, Del Tufo SN, Katzir T, Gabrieli JD, Whitfield-Gabrieli S, Chang BS
Epilepsia 2012 Jun;53(6):1024-32. Epub 2012 Apr 23 doi: 10.1111/j.1528-1167.2012.03466.x. PMID: 22524972Free PMC Article

Therapy

Akazawa Y, Ito M, Naito S, Kishikawa M, Sekine I, Nakashima M
Radiat Res 2019 Dec;192(6):666-667. Epub 2019 Sep 27 doi: 10.1667/RR15390.1. PMID: 31560638
Raza HK, Chen H, Chansysouphanthong T, Zhang Z, Hua F, Ye X, Zhang W, Dong L, Zhang S, Wang X, Cui G
Neurol Sci 2019 Mar;40(3):489-494. Epub 2018 Dec 10 doi: 10.1007/s10072-018-3667-9. PMID: 30535564
Kuwahara M, Shima M, Nakai H, Nishino M, Fukuzumi A, Yoshioka A
Acta Paediatr Jpn 1996 Jun;38(3):274-7. doi: 10.1111/j.1442-200x.1996.tb03486.x. PMID: 8741322
Franzoni E, Bernardi B, Marchiani V, Crisanti AF, Marchi R, Fonda C
Neuropediatrics 1995 Feb;26(1):37-40. doi: 10.1055/s-2007-979717. PMID: 7791949

Prognosis

Didier RA, Martin-Saavedra JS, Oliver ER, DeBari SE, Bilaniuk LT, Howell LJ, Moldenhauer JS, Adzick NS, Heuer GG, Coleman BG
AJNR Am J Neuroradiol 2020 Oct;41(10):1923-1929. Epub 2020 Sep 17 doi: 10.3174/ajnr.A6745. PMID: 32943419Free PMC Article
Liu S, Wang Z, Wei S, Liang J, Chen N, OuYang H, Zeng W, Chen L, Xie X, Jiang J
Cytogenet Genome Res 2018;154(4):201-208. Epub 2018 Apr 14 doi: 10.1159/000488692. PMID: 29656294
Gao Z, Massimi L, Rogerio S, Raybaud C, Di Rocco C
Childs Nerv Syst 2014 Jan;30(1):65-72. Epub 2013 Aug 29 doi: 10.1007/s00381-013-2249-7. PMID: 23989428
Bertholdo D, de Carvalho Neto A, Castillo M
Top Magn Reson Imaging 2011 Dec;22(6):295-302. doi: 10.1097/RMR.0b013e3182a2cca0. PMID: 24132068
Barkovich AJ, Kuzniecky RI
Neurology 2000 Dec 12;55(11):1603-8. doi: 10.1212/wnl.55.11.1603. PMID: 11187088

Clinical prediction guides

Zampeli A, Hansson B, Bloch KM, Englund E, Källén K, Strandberg MC, Björkman-Burtscher IM
Seizure 2022 Oct;101:177-183. Epub 2022 Aug 20 doi: 10.1016/j.seizure.2022.08.008. PMID: 36058100
Di Nora A, Costanza G, Pizzo F, Oliva CF, Di Mari A, Greco F, Pavone P
Acta Neurol Belg 2022 Feb;122(1):153-162. Epub 2021 Sep 1 doi: 10.1007/s13760-021-01774-3. PMID: 34471972Free PMC Article
Khoo HM, von Ellenrieder N, Zazubovits N, Hall JA, Dubeau F, Gotman J
Ann Clin Transl Neurol 2019 Jun;6(6):1010-1023. Epub 2019 May 3 doi: 10.1002/acn3.769. PMID: 31211165Free PMC Article
Peris-Celda M, Giannini C, Diehn FE, Eckel LJ, Neff BA, Van Gompel JJ
World Neurosurg 2018 Jun;114:289-292. Epub 2018 Apr 3 doi: 10.1016/j.wneu.2018.03.185. PMID: 29625310
Filippi CG, Maxwell AW, Watts R
Pediatr Radiol 2013 Sep;43(9):1196-203. Epub 2013 Mar 26 doi: 10.1007/s00247-013-2677-2. PMID: 23529629

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