Heterotopia means “out of place”. Discover the signs that it’s time to switch treatment. Roper SN, Abraham LA, Streit WJ. Brain 2012;135:1348–1369. Grey matter heterotopia is a condition in which nerve cells (neurons) do not migrate properly during the early development of the fetal brain, from about the 6th week to the 24th week of pregnancy. Periventricular gray matter heterotopia may also occur in association with other conditions such as Ehlers-Danlos syndrome, which results in extremely flexible joints, skin that stretches easily, and fragile blood vessels. Carabalona A, Beguin S, Pallesi‐Pocachard E, et al. GeneReviews® [Internet]. Gray matter heterotopia. Altered structure or function of the proteins produced by the DCX or PAFAH1B1 gene impairs important interactions that are needed for neuronal migration. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Gray matter heterotopia affected individuals typically have seizures and/or developmental delay or behavioral problems. The white matter at the cord’s periphery contains ascending and descending tracts of myelinated sensory and motor nerve fibers. In a few cases, periventricular gray matter heterotopia has been associated with abnormalities in chromosome 5. Coagulopathy and cardiovascular abnormalities have been observed in some patients 31). 2009;30(1):4-11. doi:10.3174/ajnr.A1223 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051699, Watrin, F., Manent, J.‐B., Cardoso, C. and Represa, A. In about 50 percent of cases of X-linked periventricular gray matter heterotopia, an affected person inherits the mutation from a mother who is also affected. Scientifica (Cairo) 2012;2012:480129. Epilepsy Res. Along with epilepsy, further manifestations of gray matter heterotopia are represented by mild intellectual disability, developmental delay and motor impairments and dyslexia involving impairments in reading ability, processing speed, and executive functioning 50). There is a female predominance in cases of bilateral periventricular nodular heterotopia. Certain types of gray matter heterotopia have also been found to be associated with metabolic disorders such as neonatal adrenoleukodystrophy, connective tissue disorders such as Ehlers-Danlos syndrome and a number of congenital central nervous system malformations and these associated anomalies will also affect symptomatology. MEKK4 signaling regulates filamin expression and neuronal migration. The brefeldin A‐inhibited GDP/GTP exchange factor 2, a protein involved in vesicular trafficking, interacts with the beta subunits of the GABA receptors. It is recommended that people with the X-linked form of periventricular nodular heterotopia have studies evaluating the carotid artery and an abdominal ultrasound, due to the risk for aortic or carotid dissection or other vascular anomalies 69). The number of neurons is clearly important, but so is the connectivity of the neuronal network. Once there is a picture of damage to the brain, the tables are turned on the insurance company. Affected individuals usually have normal intelligence, although some have mild intellectual disability. Talk to your doctor to learn more about the potential effects of MS, as well as your treatment options. Robertson SP. Most affected individuals are female 20). Neuropsychiatric disease in patients with periventricular heterotopia. Classification system for malformations of cortical development: Update 2001. Traditionally, multiple sclerosis (MS) is considered to be a disease primarily affecting the white matter (WM). “Is it just simply the way that each individual responds to the same injury, or does each person actually have different underlying injuries to the white matter… Although such surgery cannot reverse developmental disabilities, it may provide full or partial relief from seizures. Furthermore, these structural changes are greater in those that report more PCS symptoms, suggesting a neurophysiological basis for these persistent symptoms. In the brain, FLNA is expressed at high levels in prenatal and neonatal stages and these levels diminish during adolescence to reach moderate expression in adulthood 27). Rare mutations or microdeletion of autosomal genes 23) may result further in syndromic disorders. White matter brain disease results in the degeneration of white matter, which creates a large portion of the brain. GeneReviews® [Internet]. There are conflicting reports as to whether the phenomenon has been found in normal persons 9). List of principal neurological and psychiatric conditions associated with gray matter heterotopia 59), 60), 61): The most common neuropsychiatric clinical picture is that of intellectual disability, which ranges from mild to severe in nature, even though many patients with gray matter heterotopia present with normal intellectual functioning 62). Neurological deficits and developmental delay, in particular, depend on the type and severity of the gray matter heterotopia as well as the location of the lesions. Neuroblasts proliferate in the germinal matrix between 7 and 8 weeks of gestation. 10.1111/cns.12322, Felker MV, Walker LM, Sokol DK, Edwards-Brown M, Chang BS. White matter damage has long been a concern among premature babies, but full-term babies sometimes also display the damage—and its related symptoms. The 2 unique types of disease activity seen in patients with MS are White Matter (WM) pathology and Grey Matter (GM) pathology. Varying results from surgical resection of the affected area have been reported. BIG2 is thought to carry out ARF‐dependent vesicle trafficking along these subcellular compartments 35). The signs and symptoms of the condition depend on the size of the bands and the lack of development of the cerebral cortex. Gray matter heterotopia also called grey matter heterotopia, is a relatively common malformation of cortical development, where cortical cells (grey matter) are present in inappropriate locations in the brain, due to interruption in their migration to their correct location in the cerebral cortex 1). 2020;11:261. Different types of cerebral palsy are associated with different types of matter injury in the brain. Mutations in the DCX or PAFAH1B1 gene cause subcortical band heterotopia. google_ad_client: "ca-pub-9759235379140764", Unilateral periventricular nodular heterotopia can co-occur with subcortical nodular heterotopia and with polymicrogyria. Grey matter heterotopia can co-occur with other structural abnormalities. There is evidence for both white and grey matter damage in participants with mTBI over 1 year after injury. Neurology 2001;57;2168-2178 https://geiselmed.dartmouth.edu/radiology/wp-content/uploads/sites/47/2019/04/Classification-System-for-Malformations-of-Cortical-Development-2001-Update-Barkovich.pdf, Battaglia, G., Chiapparini, L., Franceschetti, S., Freri, E., Tassi, L., Bassanini, S., Villani, F., Spreafico, R., D’Incerti, L. and Granata, T. (2006), Periventricular Nodular Heterotopia: Classification, Epileptic History, and Genesis of Epileptic Discharges. Traumatic brain injury often results in persistent disability, due particularly to cognitive impairments (Whitnall et al., 2006). Filamins as integrators of cell mechanics and signalling. 2000;55:1603–8. There is a wide spectrum of anatomic and clinical presentations of periventricular nodular heterotopia, ranging from asymptomatic small unilateral or bilateral nodules to extensive agglomerates of heterotopia lining the lateral ventricles in patients with intractable epilepsy and intellectual disabilities 13). Dyspraxia (difficulties with coordinated movement) and problems with fine motor skills have also been found 52). J Pychiatr Intensive Care. Difficulty with reading and spelling (dyslexia) and movement problems have been reported in some people with periventricular gray matter heterotopia. DCX-Related Disorders. 1998;10:351–3. Epilepsy Behav. Gray matter heterotopia may be unilateral or bilateral, singular or multiple, separate or contiguous. Periventricular nodular heterotopia in 22q11. Also learn about side effects, other safety considerations…. Mutations in the X‐linked filamin 1 gene cause periventricular nodular heterotopia in males as well as in females. Mutations in the ARFGEF2 gene may disrupt this function, which could result in the abnormal neuronal migration seen in periventricular gray matter heterotopia. See how Hopkins clinicians are teaming to provide a better assessment of this often overlooked damage. These cases occur in people with no history of the disorder in their family. 2007;2(2):118–21. Filamin A: phenotypic diversity. J Neurochem 2004;90:173–189. Subependymal Heterotopia With Psychosis and Imperforate Anus in a Female Patent. Bilateral periventricular nodular heterotopia can co-occur with cerebellar vermis hypoplasia and hypoplasia of the corpus callosum. 10.1016/0010-440X(92)90063-V, Esquenazi Y, Kalamangalam GP, Slater JD, Knowlton RC, Friedman E, Morris SA, Shetty A, Gowda A, Tandon N. Stereotactic laser ablation of epileptogenic periventricular nodular heterotopia. Shin H, Shinotsuka C, Nakayama K. Expression of BIG2 and analysis of its function in mammalian cells. Can lose cells: Underdevelopment of the gray matter is something your born with and symptoms of what would be perceived as mental retardation at that age.. Sheen VL. grey matter lesions (Figure 1), the causes of grey matter damage and its relationship to white matter lesions remain unclear. Five different groups of periventricular nodular heterotopia have been distinguished 16): (1) bilateral and symmetrical; (2) bilateral single-noduled; (3) bilateral and asymmetrical; (4) unilateral; and (5) unilateral with extension to neocortex. These teratogens produce damages within the proliferative neuroepithelium, affecting both the genesis of newborn neurons and their migration along the radial glial scaffold 47). People with specific questions about genetic risks or genetic testing for themselves or family members should speak with a genetics professional. However, the development of some clinical symptoms such as cognitive impairment cannot be fully explained by the severity of WM pathology alone. In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. -- The mental impairment and problems with walking experienced by patients with multiple sclerosis (MS) are linked to damage in the brain's gray matter, … J Neuropsychiatry Clin Neurosci. Associated anomalies include 5): Gray matter heterotopia may constitute about 15% of cortical developmental malformations and may be found in about 2% of patients with epilepsy 6). Individuals with periventricular gray matter heterotopia in whom ARFGEF2 gene mutations have been identified have a severe form of the disorder, including microcephaly, severe developmental delay, and seizures beginning in infancy. Early and consistent treatment may help limit the effects of MS on the brain and other areas of the body. Sheen VL, Dixon PH, Fox JW, et al. Footnote: A and B, Coronal T1-weighted images show a few small periventricular nodules, isointense to the gray matter, along the lateral ventricular wall. This gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. This gene provides instructions for making a protein that is involved in the movement (trafficking) of small sac-like structures (vesicles) within the cell. 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