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Periventricular heterotopia

MedGen UID:
1766888
Concept ID:
C5399973
Disease or Syndrome
Synonyms: Periventricular gray matter heterotopias; Subependymal gray matter heterotopia
 
HPO: HP:0007165

Definition

A form of gray matter heterotopia were the mislocalized gray matter is typically located periventricularly, also sometimes called subependymal heterotopia. Periventricular means beside the ventricles. This is by far the most common location for heterotopia. Subependymal heterotopia present in a wide array of variations. There can be a small single node or a large number of nodes, can exist on either or both sides of the brain at any point along the higher ventricle margins, can be small or large, single or multiple, and can form a small node or a large wavy or curved mass. [from HPO]

Conditions with this feature

Fragile X syndrome
MedGen UID:
8912
Concept ID:
C0016667
Disease or Syndrome
FMR1 disorders include fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency (FXPOI). Fragile X syndrome occurs in individuals with an FMR1 full mutation or other loss-of-function variant and is nearly always characterized in affected males by developmental delay and intellectual disability along with a variety of behavioral issues. Autism spectrum disorder is present in 50%-70% of individuals with FXS. Affected males may have characteristic craniofacial features (which become more obvious with age) and medical problems including hypotonia, gastroesophageal reflux, strabismus, seizures, sleep disorders, joint laxity, pes planus, scoliosis, and recurrent otitis media. Adults may have mitral valve prolapse or aortic root dilatation. The physical and behavioral features seen in males with FXS have been reported in females heterozygous for the FMR1 full mutation, but with lower frequency and milder involvement. FXTAS occurs in individuals who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor followed by cognitive impairment. Psychiatric disorders are common. Age of onset is typically between 60 and 65 years and is more common among males who are hemizygous for the premutation (40%) than among females who are heterozygous for the premutation (16%-20%). FXPOI, defined as hypergonadotropic hypogonadism before age 40 years, has been observed in 20% of women who carry a premutation allele compared to 1% in the general population.
Smith-Lemli-Opitz syndrome
MedGen UID:
61231
Concept ID:
C0175694
Disease or Syndrome
Smith-Lemli-Opitz syndrome (SLOS) is a congenital multiple-anomaly / cognitive impairment syndrome caused by an abnormality in cholesterol metabolism resulting from deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase. It is characterized by prenatal and postnatal growth restriction, microcephaly, moderate-to-severe intellectual disability, and multiple major and minor malformations. The malformations include distinctive facial features, cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes. The clinical spectrum is wide; individuals with normal development and only minor malformations have been described.
Periventricular heterotopia with microcephaly, autosomal recessive
MedGen UID:
334110
Concept ID:
C1842563
Disease or Syndrome
Genitopatellar syndrome
MedGen UID:
381208
Concept ID:
C1853566
Disease or Syndrome
KAT6B disorders include genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) which are part of a broad phenotypic spectrum with variable expressivity; individuals presenting with a phenotype intermediate between GPS and SBBYSS have been reported. Both phenotypes are characterized by some degree of global developmental delay / intellectual disability; hypotonia; genital abnormalities; and skeletal abnormalities including patellar hypoplasia/agenesis, flexion contractures of the knees and/or hips, and anomalies of the digits, spine, and/or ribs. Congenital heart defects, small bowel malrotation, feeding difficulties, slow growth, cleft palate, hearing loss, and dental anomalies have been observed in individuals with either phenotype.
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.
Methylmalonate semialdehyde dehydrogenase deficiency
MedGen UID:
481470
Concept ID:
C3279840
Disease or Syndrome
Methylmalonate semialdehyde dehydrogenase deficiency is a rare autosomal recessive inborn error of metabolism with a highly variable phenotype. Some patients may be asymptomatic, whereas others show global developmental delay, nonspecific dysmorphic features, and delayed myelination on brain imaging. Laboratory studies typically show increased urinary 3-hydroxyisobutyric acid, although additional metabolic abnormalities may also be observed (summary by Marcadier et al., 2013).
Microcephaly and chorioretinopathy 2
MedGen UID:
863825
Concept ID:
C4015388
Disease or Syndrome
Microcephaly and chorioretinopathy-2 is an autosomal recessive developmental disorder characterized by delayed psychomotor development, visual impairment, and short stature (summary by Martin et al., 2014). For a discussion of genetic heterogeneity of microcephaly and chorioretinopathy, see MCCRP1 (251270).
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).
Orofaciodigital syndrome type 14
MedGen UID:
1635470
Concept ID:
C4706604
Disease or Syndrome
A rare subtype of orofaciodigital syndrome, with autosomal recessive inheritance and C2CD3 mutations. The disease has characteristics of severe microcephaly, trigonocephaly, severe intellectual disability and micropenis, in addition to oral, facial and digital malformations (gingival frenulum, lingual hamartomas, cleft/lobulated tongue, cleft palate, telecanthus, up-slanting palpebral fissures, microretrognathia, postaxial polydactyly of hands and duplication of hallux). Corpus callosum agenesis and vermis hypoplasia with molar tooth sign on brain imaging are also associated.
Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations
MedGen UID:
1648439
Concept ID:
C4748927
Disease or Syndrome
Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM) is an autosomal dominant neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, and characteristic brain abnormalities on brain imaging. Affected individuals have enlargement of the corpus callosum, enlarged ventricles, and cerebellar and brainstem hypoplasia. Other features may include lack of speech development, gait instability, and seizures. Some patients with MAST1 mutations may have impaired intellectual development and/or autism spectrum disorder without significant findings on brain imaging (summary by Tripathy et al., 2018).
Brain abnormalities, neurodegeneration, and dysosteosclerosis
MedGen UID:
1678789
Concept ID:
C5193117
Disease or Syndrome
Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) is an autosomal recessive disorder characterized by brain abnormalities, progressive neurologic deterioration, and sclerotic bone dysplasia similar to dysosteosclerosis (DOS). The age at onset is highly variable: some patients may present in infancy with hydrocephalus, global developmental delay, and hypotonia, whereas others may have onset of symptoms in the late teens or early twenties after normal development. Neurologic features include loss of previous motor and language skills, cognitive impairment, spasticity, and focal seizures. Brain imaging shows periventricular white matter abnormalities and calcifications, large cisterna magna or Dandy-Walker malformation, and sometimes agenesis of the corpus callosum (summary by Guo et al., 2019).
Neuromuscular disease and ocular or auditory anomalies with or without seizures
MedGen UID:
1684689
Concept ID:
C5231483
Disease or Syndrome
Skeletal dysplasia, mild, with joint laxity and advanced bone age
MedGen UID:
1711043
Concept ID:
C5394341
Disease or Syndrome
CSGALNACT1 deficiency is characterized by mild skeletal dysplasia, joint hypermobility, and advanced bone age. Shortness of long bones is evident prenatally, and patients exhibit short stature and relative macrocephaly. Advanced carpotarsal bone age and monkey-wrench appearance of the femur observed in infancy may disappear with age (Mizumoto et al., 2020).
Agenesis of corpus callosum, cardiac, ocular, and genital syndrome
MedGen UID:
1718475
Concept ID:
C5394523
Disease or Syndrome
Agenesis of corpus callosum, cardiac, ocular, and genital syndrome (ACOGS) is a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, corpus callosum agenesis or hypoplasia, craniofacial dysmorphisms, and ocular, cardiac, and genital anomalies (Accogli et al., 2019).
Li-Ghorbani-Weisz-Hubshman syndrome
MedGen UID:
1763263
Concept ID:
C5436525
Disease or Syndrome
Li-Ghorbani-Weisz-Hubshman syndrome (LIGOWS) is a neurodevelopmental disorder characterized by global developmental delay, mild to moderately impaired intellectual development with language delay, and mild dysmorphic features. Affected individuals may have behavioral abnormalities and difficulties with numbers and understanding certain concepts, such as money. Some patients have seizures. Brain imaging often shows enlarged ventricles, thin corpus callosum, and gray matter nodular heterotopia, suggesting abnormal cortical brain development. More variable additional features may be present (summary by Li et al., 2020).
Neurodevelopmental disorder with neuromuscular and skeletal abnormalities
MedGen UID:
1803456
Concept ID:
C5676965
Disease or Syndrome
Neurodevelopmental disorder with neuromuscular and skeletal abnormalities (NEDNMS) is an autosomal recessive disorder characterized by global developmental delay apparent from infancy or early childhood. The severity of the disorder is highly variable. Affected individuals show impaired intellectual development and motor delay associated with either severe hypotonia or hypertonia and spasticity. Most affected individuals have skeletal defects and dysmorphic facial features. Some may have ocular or auditory problems, peripheral neuropathy, behavioral abnormalities, and nonspecific findings on brain imaging (Kurolap et al., 2022).
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).

Professional guidelines

PubMed

Lin YJ, Chiu NC, Chen HJ, Huang JY, Ho CS
Pediatr Neonatol 2021 Mar;62(2):158-164. Epub 2020 Nov 2 doi: 10.1016/j.pedneo.2020.10.012. PMID: 33214065
Righini A, Zirpoli S, Mrakic F, Parazzini C, Pogliani L, Triulzi F
AJNR Am J Neuroradiol 2004 Feb;25(2):343-6. PMID: 14970044Free PMC Article

Recent clinical studies

Etiology

Giuliani L, Di Toro A, Urtis M, Narula N, Grasso M, Pelenghi S, Belliato M, Bozzani A, Arici V, Pellegrini C, Serio A, Pilotto A, Fergnani V, Antoniazzi E, Magrassi L, Dore R, Valentini A, Preda L, Calliada F, Quaretti P, Pirrelli S, Kodama T, Vricella L, Cameron D, Arbustini E
J Am Coll Cardiol 2023 Mar 14;81(10):979-991. doi: 10.1016/j.jacc.2023.01.005. PMID: 36889877
Lu YT, Hsu CY, Liu YT, Chan CK, Chuang YC, Lin CH, Chang KP, Ho CJ, Ng CC, Lim KS, Tsai MH
Biomed J 2022 Jun;45(3):542-548. Epub 2021 May 20 doi: 10.1016/j.bj.2021.05.003. PMID: 35660364Free PMC Article
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
Romero DM, Bahi-Buisson N, Francis F
Semin Cell Dev Biol 2018 Apr;76:33-75. Epub 2017 Oct 11 doi: 10.1016/j.semcdb.2017.09.031. PMID: 28951247
Guerrini R, Parrini E
Neurobiol Dis 2010 May;38(2):154-66. Epub 2009 Feb 23 doi: 10.1016/j.nbd.2009.02.008. PMID: 19245832

Diagnosis

Giuliani L, Di Toro A, Urtis M, Narula N, Grasso M, Pelenghi S, Belliato M, Bozzani A, Arici V, Pellegrini C, Serio A, Pilotto A, Fergnani V, Antoniazzi E, Magrassi L, Dore R, Valentini A, Preda L, Calliada F, Quaretti P, Pirrelli S, Kodama T, Vricella L, Cameron D, Arbustini E
J Am Coll Cardiol 2023 Mar 14;81(10):979-991. doi: 10.1016/j.jacc.2023.01.005. PMID: 36889877
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
Arya R, Spaeth C, Zhang W
Epileptic Disord 2021 Apr 1;23(2):392-396. doi: 10.1684/epd.2021.1258. PMID: 33772511
Verrotti A, Monacelli D, Castagnino M, Villa MP, Parisi P
Seizure 2014 Nov;23(10):819-24. Epub 2014 Jul 30 doi: 10.1016/j.seizure.2014.07.014. PMID: 25131162
Lu J, Sheen V
Epilepsy Behav 2005 Sep;7(2):143-9. doi: 10.1016/j.yebeh.2005.05.001. PMID: 15996530

Therapy

Kobayashi Y, Ishikawa N, Tani H, Fujii Y, Kobayashi M
Neuropediatrics 2017 Apr;48(2):119-122. Epub 2017 Jan 23 doi: 10.1055/s-0037-1598111. PMID: 28114705
Venkatesan C, Angle B, Millichap JJ
Epileptic Disord 2016 Jun 1;18(2):195-200. doi: 10.1684/epd.2016.0828. PMID: 27248490
de Wit MC, Schippers HM, de Coo IF, Arts WF, Lequin MH, Brooks A, Visser GH, Mancini GM
Seizure 2010 Sep;19(7):450-2. Epub 2010 Jul 15 doi: 10.1016/j.seizure.2010.06.013. PMID: 20637656
Sheen VL, Basel-Vanagaite L, Goodman JR, Scheffer IE, Bodell A, Ganesh VS, Ravenscroft R, Hill RS, Cherry TJ, Shugart YY, Barkovich J, Straussberg R, Walsh CA
Brain Dev 2004 Aug;26(5):326-34. doi: 10.1016/j.braindev.2003.09.004. PMID: 15165674
Russo GL, Tassi L, Cossu M, Cardinale F, Mai R, Castana L, Colombo N, Bramerio M
Epileptic Disord 2003 Sep;5 Suppl 2:S115-23. PMID: 14617430

Prognosis

Hiraide T, Shimizu K, Okumura Y, Miyamoto S, Nakashima M, Ogata T, Saitsu H
J Hum Genet 2023 Jul;68(7):499-505. Epub 2023 Mar 10 doi: 10.1038/s10038-023-01143-3. PMID: 36894704
Giuliani L, Di Toro A, Urtis M, Narula N, Grasso M, Pelenghi S, Belliato M, Bozzani A, Arici V, Pellegrini C, Serio A, Pilotto A, Fergnani V, Antoniazzi E, Magrassi L, Dore R, Valentini A, Preda L, Calliada F, Quaretti P, Pirrelli S, Kodama T, Vricella L, Cameron D, Arbustini E
J Am Coll Cardiol 2023 Mar 14;81(10):979-991. doi: 10.1016/j.jacc.2023.01.005. PMID: 36889877
Tittle BJ, Maheshwari M, Marashly A
Epileptic Disord 2022 Oct 1;24(5):795-802. doi: 10.1684/epd.2022.1450. PMID: 35792848
Verrotti A, Spartà MV, Monacelli D, Porto R, Castagnino M, Russo Raucci A, Compagno F, Viglio S, Foiadelli T, Nicita F, Grosso S, Spalice A, Chiarelli F, Marseglia G, Savasta S
Epilepsia 2014 Aug;55(8):1213-9. Epub 2014 Jun 25 doi: 10.1111/epi.12699. PMID: 24965265
Moro F, Carrozzo R, Veggiotti P, Tortorella G, Toniolo D, Volzone A, Guerrini R
Neurology 2002 Mar 26;58(6):916-21. doi: 10.1212/wnl.58.6.916. PMID: 11914408

Clinical prediction guides

Giuliani L, Di Toro A, Urtis M, Narula N, Grasso M, Pelenghi S, Belliato M, Bozzani A, Arici V, Pellegrini C, Serio A, Pilotto A, Fergnani V, Antoniazzi E, Magrassi L, Dore R, Valentini A, Preda L, Calliada F, Quaretti P, Pirrelli S, Kodama T, Vricella L, Cameron D, Arbustini E
J Am Coll Cardiol 2023 Mar 14;81(10):979-991. doi: 10.1016/j.jacc.2023.01.005. PMID: 36889877
Lu YT, Hsu CY, Liu YT, Chan CK, Chuang YC, Lin CH, Chang KP, Ho CJ, Ng CC, Lim KS, Tsai MH
Biomed J 2022 Jun;45(3):542-548. Epub 2021 May 20 doi: 10.1016/j.bj.2021.05.003. PMID: 35660364Free PMC Article
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
Arya R, Spaeth C, Zhang W
Epileptic Disord 2021 Apr 1;23(2):392-396. doi: 10.1684/epd.2021.1258. PMID: 33772511
Vandervore LV, Schot R, Kasteleijn E, Oegema R, Stouffs K, Gheldof A, Grochowska MM, van der Sterre MLT, van Unen LMA, Wilke M, Elfferich P, van der Spek PJ, Heijsman D, Grandone A, Demmers JAA, Dekkers DHW, Slotman JA, Kremers GJ, Schaaf GJ, Masius RG, van Essen AJ, Rump P, van Haeringen A, Peeters E, Altunoglu U, Kalayci T, Poot RA, Dobyns WB, Bahi-Buisson N, Verheijen FW, Jansen AC, Mancini GMS
Brain 2019 Apr 1;142(4):867-884. doi: 10.1093/brain/awz045. PMID: 30879067Free PMC Article

Recent systematic reviews

Di Mascio D, Sileo FG, Khalil A, Rizzo G, Persico N, Brunelli R, Giancotti A, Panici PB, Acharya G, D'Antonio F
Ultrasound Obstet Gynecol 2019 Aug;54(2):164-171. Epub 2019 Jul 11 doi: 10.1002/uog.20197. PMID: 30549340

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