Ehlersdanlos syndromes are a group of connective tissue disorders that can be inherited and are varied both in how affect the body and in their genetic causes. Pvnh4, formerly other entities represented in this entry. Location of periventricular nodular heterotopia is related to. The purpose of this study was to determine whether specific malformation phenotypes may be related to location, side, or number of pnh as assessed by mr imaging. Ehlers danlos syndromes nord national organization for. Periventricular heterotopia ph is a brain malformation characterised by heterotopic. Filamin a mutations cause periventricular heterotopia with ehlersdanlos.
Connective tissue is a complex mixture of proteins and other substances that provide strength and elasticity to the underlying structures in your body. Periventricular heterotopia may also occur in association with other conditions such as ehlersdanlos syndrome ehlersdanlos with periventricular heterotopia, which also results in extremely flexible joints, skin that stretches easily, and fragile blood vessels. Four eds variants arthrocalasia, classic with vascular rupture. Clinical genetics publications, clinical genetics group. Classic ehlersdanlos syndrome is a heritable connective tissue disorder characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars, easy bruising, and generalized joint hypermobility. People with this condition typically develop recurrent seizures epilepsy beginning in midadolescence. Genes related to ehlersdanlos syndrome with periventricular heterotopia flna. Col3a1 homepage ehlers danlos syndrome variant database. Books hypermobility, fibromyalgia and chronic pain alan j hakim herausgeber, rosemary j. Periventricular heterotopia with complete agenesis of the. Copy number variation mapping was performed using affymetrix 250k nspi array. We now know that rare disorder is pvnh4, for short, or xlinked periventricular nodular heteropia with ehlersdanlos syndrome.
Increasingly, the ehlersdanlos variant of pvnh is considered to fall within the spectrum of xlinked pvnh caused by pathogenic variants in. Filamin a mutations cause periventricular heterotopia with ehlersdanlos syndrome. Ehlers danlos syndrome comprises a heterogeneous group of collagen disorders hereditary connective tissue disease. Periventricular nodular heterotopia pnh is a human neuronal migration disorder characterised by seizures and conglomerates of neural cells around the lateral ventricles of the brain, caused by flna mutations. Ehlers danlos syndromes are a group of connective tissue disorders that can be inherited and are varied both in how affect the body and in their genetic causes. This means that heterotopia, periventricular, or a subtype of heterotopia, periventricular, affects less than 200,000 people in the us population. Periventricular heterotopia genetic and rare diseases. The nodules are thought to reflect impaired migration from the vz. Walsh, md, phd nature often employs similar mechanisms to complete similar tasks, thus the evolution of homologous proteins across various organ systems to perform similar but slightly different.
Flna encodes filamin a, an actin binding protein involved in cytoskeletal. A cause of epilepsy and periventricular heterotopia alberto b verrottia, debora monacellia, miriam castagninoa, maria pia villa, pasquale parisib, adepartment b ofpediatrics, university perugia, italy child. Periventricular heterotopia genetics home reference nih. The collagen defect has been identified in at least six of the many types of ehlersdanlos syndrome. Ehlersdanlos syndrome eds with periventricular heterotopia is a newly described variant of eds. Heterotopia periventricular nodular ligada al cromosoma x. Ehlers danlos national foundation usa and ehlers danlos support group uk. They are generally characterized by joint hypermobility joints that stretch further than normal, skin hyperextensibility skin that can be stretched further than normal, and tissue fragility. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to lifethreatening complications. Autism, joint hypermobilityrelated disorders and pain. Filamin a mutations cause periventricular heterotopia with. Affected people are frequently short, and have thin scalp hair. Query the database by selecting the most important variables exon number, type of variant, disease phenotype advanced search.
Periventricular heterotopia ph refers to a malformation of cortical development characterized by bilateral nearcontiguous ectopic neuronal nodules found along the lateral ventricles sotermed periventricular heterotopia. Although many dermatology books continue to include both classifications, the ehlersdanlos syndrome clinical forms can now be classified as follows. Mutations of fibrillar collagens i, ii, iii, iv, v, vi, ix and xii or enzymes involved in their biosynthesis i. These most common clinical manifestations among patients, carrying flna mutations and affected by eds and ph, led some authors to suggest a separate syndrome, termed as ehlersdanlos syndromeperiventricular heterotopia variant edsph. We also discussed the possible consequences on child neurological outcome. Plod1, chst14 are responsible for the multisystemic affection involving skin, ligaments, muscles, vessels, hollow. A nondegenerate code of deleterious variants in mendelian loci contributes to complex disease risk. Periventricular nodular heterotopia are common malformations of cortical development that are associated with many clinical syndromes and with many different neuroimaging phenotypes. There is also another form of neuronal heterotopia disorder called subcortical band heterotopia, also known as double cortex. In most cases, periventricular heterotopia is caused by mutations in the flna gene.
The ehlersdanlos syndrome eds comprises a group of hereditary connective tissue disorders. Periodontitis type of ehlers danlos syndrome eds type viii is distinguished from other subtypes of eds by severe periodontitis leading to premature loss of permanent teeth. Pvnh can sometimes happen with other disorders such as ehlers danlos syndrome, or polymicrogyria. The flna gene is associated with xlinked periventricular heterotopia medgen uid. Oct 06, 2015 periventricular heterotopia may also occur in association with other conditions such as ehlers danlos syndrome ehlers danlos with periventricular heterotopia, which also results in extremely flexible joints, skin that stretches easily, and fragile blood vessels. Ehlersdanlos syndrome type iv orphanet journal of rare. Ehlersdanlos syndromes are a group of connective tissue disorders that can be. The col5a1 and col5a2 genes cause ehlers danlos syndrome, classic type type i and type. Xlinked periventricular heterotopia or flnarelated periventricular nodular heterotopia is a genetic disorder in which nerve cells in the brain do not migrate properly during early fetal development a neuronal migration disorder. It comprises ehlers danlos syndrome type i and ehlers danlos syndrome type ii, but it is. Keer herausgeber, rodney grahame herausgeber a multidisciplinary approach to managing ehlersdanlos type iii hypermobility syndrome.
They suggested that these anomalies are not part of a separate entity previously designated an ehlersdanlos variant of pvnh but variable expressions of pvnh1 for which all patients with this disorder should be evaluated. The hdcts includes classically marfan syndrome, ehlersdanlos syndromes. Pathogenic variants in flna have been identified in rare individuals who have periventricular nodular heterotopia and also exhibit features of ehlers danlos syndrome including joint hypermobility, skin fragility, andor aortic aneurysms. It is also characterized by fragile blood vessels and organs that can easily rupture. Ehlers danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Xlinked periventricular heterotopia genetic and rare.
Pathogenic variants in flna have been identified in rare individuals who have periventricular nodular heterotopia and also exhibit features of ehlersdanlos syndrome including joint hypermobility, skin fragility, andor aortic aneurysms. These are things like tendons and ligaments that hold parts of your body together. 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. The vascular form, sometimes referred to as type iv, is. Walsh, md, phd nature often employs similar mechanisms to complete similar tasks, thus the evolution of homologous proteins across various organ systems to. Ehlersdanlos syndromes eds are frequently associated with epilepsy. Ehlersdanlos syndrome eds is a disease that weakens the connective tissues of your body. In addition to several gene mutations, choromosomal abnormalities can cause neuronal heterotopia disorder. In normal brain development, neurons form in the periventricular region, located around fluidfilled cavities. Aug 11, 2006 sheen vl, jansen a, chen mh, parrini e, morgan t, ravenscroft r, et al. Genetics of periventricular heterotopia and ehlersdanlos syndrome. Vascular type ehlersdanlos syndrome is associated with. Periventricular 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 nodular heterotopia is a neuronal migration disorder in which neurons are located in an.
Nevertheless, the latest eds nosology excluded this rare variant from the spectrum disorder. Genetics of periventricular heterotopia and ehlers danlos syndrome. Ehlersdanlos syndrome eds is a rare connective tissue disorder with multitude heterogeneous symptoms. These most common clinical manifestations among patients, carrying flna mutations and affected by eds and ph, led some authors to suggest a separate syndrome, termed as ehlers danlos syndrome periventricular heterotopia variant edsph. Ehlersdanlos syndrome comprises a variety of inherited connective tissue disorders. Another name for periventricular laminar heterotopia or close medical condition. Clinical and genetic aspects of ehlersdanlos syndrome. Oct, 2017 ehlersdanlos syndrome is a group of inherited disorders that affect your connective tissues primarily your skin, joints and blood vessel walls. Clinical presentation clinically manifests by skin hyperelasticity and. Danlos syndrome eds comprises a group of hereditary connective tissue disorders.
Short stature, blue sclerae, thin and hyperelastic skin, muscle atrophy. Molecular pathology defects in flna, which encodes filamin a, an actinbinding protein, cause. Joint hypermobility and ringing in ears symptom checker. Sheen vl, jansen a, chen mh, parrini e, morgan t, ravenscroft r, et al. Ehlersdanlos syndrome symptoms and causes mayo clinic. Epidemiology there is a recognized male predominance. Periventricular heterotopia is a condition in which the nerve cells neurons do not migrate properly during early development of the fetal brain. We analyzed the possible association with epilepsy and periventricular heterotopia. Core ehlersdanlos syndrome panel genes col3a1, col5a1. Ehlersdanlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. The spectrum of skin manifestations includes skin hyperextensibility, easy bruising, pretibial discoloration, dystrophic scar formation.
Query the database by selecting a combination of variables. Periventricular heterotopia ph has been interpreted as a disorder in neuronal migration where newly born neurons fail to migrate from their birthplace along the lining of the lateral ventricles of the brain, thereby giving rise to the characteristic ectopically placed neuronal nodules figure 1. Periventricular nodular heterotopia with frontometaphyseal dysplasia. Source national institutes of health nih heterotopia, periventricular as a disease. This condition can be associated with various neurological features. Ehlersdanlos syndrome eds is a heterogeneous group of inherited connectivetissue disorders characterized by joint hypermobility, cutaneous fragility, and hyperextensibility. Periventricular heterotopia variant pvnh4 epilepsy, cardiac defects, joint hypermobility. Filamin a mutations cause periventricular heterotopia with ehlers danlos. Vascular eds formerly categorized as type 4 is identified by skin that is thin, translucent, extremely fragile, and bruises easily. We now know that rare disorder is pvnh4, for short, or xlinked periventricular nodular heteropia with ehlers danlos syndrome.
Ehlersdanlos syndrome eds is an umbrella term which encompasses a heterogeneous group of connective tissue disorders with distinct inheritance patterns, biochemical defects, and prognostic implications byers 1997, beighton et al. The purpose of this study was to determine whether specific malformation phenotypes may be related to location, side, or number of pnh as assessed by mr. The flna gene causes flnarelated periventricular nodular heterotopia pvnh. These most common clinical manifestations among patients, carrying flna mutations and affected by eds and ph, led some authors to suggest a separate syndrome, termed as ehlersdanlos syndrome periventricular heterotopia variant edsph. Ehlersdanlos variant of periventricular heterotopia ph, in part, represents an overlapping syndrome with xlinked dominant ph due to filamin a mutations.
Ehlers danlos syndrome eds is a rare connective tissue disorder with multitude heterogeneous symptoms. We also found out at around the same time it span three generations in my family, confirmed with my mom, myself and of course ella being all affected at various levels. Ehlersdanlos syndrome comprises a heterogeneous group of collagen disorders hereditary connective tissue disease. Periventricular heterotopia in common microdeletion syndromes. Ehlers danlos syndrome variant database collagen type iii alpha 1 chain col3a1 lovd v. Ehlersdanlos syndrome with periventricular heterotopia the association of a brain malformation periventricular nodular heterotopia with a connective tissue disorder called ehlersdanlos syndromemore. Apr 20, 2017 xlinked periventricular heterotopia or flnarelated periventricular nodular heterotopia is a genetic disorder in which nerve cells in the brain do not migrate properly during early fetal development a neuronal migration disorder. The ehlers danlos syndrome eds comprises a group of hereditary connective tissue disorders. Ehlersdanlos syndrome type iv, the vascular type of ehlersdanlos syndromes eds, is an inherited connective tissue disorder defined by characteristic facial features acrogeria in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed.
Marfan syndrome mfs is an autosomal dominant genetic disorder affecting the connective tissue that occurs in approximately 1 to 2 per 10,000 individuals. Ehlersdanlos syndrome and periventricular nodular heterotopia. Mutations of the alpha2v chain type v collagen impair matrix assembly and produce ehlers danlos syndrome type i. Jul 19, 2007 ehlers danlos syndrome type iv, the vascular type of ehlers danlos syndromes eds, is an inherited connective tissue disorder defined by characteristic facial features acrogeria in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed. Tnxb homepage ehlers danlos syndrome variant database. It comprises ehlersdanlos syndrome type i and ehlersdanlos syndrome type ii, but it is. Periventricular leukomalacia definition of periventricular. Eds with periventricular heterotopia, xlinked recessive, flna, arfgef2, nodular brain. Core ehlersdanlos syndrome panel genes col3a1, col5a1, col5a2. Ehlersdanlos syndrome, classic type ncbi bookshelf. Pathogenic variants in flna have been identified in a limited number of individuals with periventricular nodular heterotopia a neuronal migration disorder characterized by seizures and conglomerates of neural cells around the lateral ventricles of the brain and features of eds. It is characterized by the presence of skeletal, ocular, and cardiovascular manifestations and is caused by variants in the fbn1 gene. It is characterized by the presence of clumps of neurons near the brains ventricles.
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