Periventricular nodular heterotopia (PVNH) is a rare neurological disorder, described in the medical litterature as a neuronal migration disorder, and which belongs to the large group of cortical malformations of development. It is characterized by the presence of nodules of neurons (grey matter) in the wrong spot, specifically along the lateral ventricles instead of properly migrating to the cortex. It can also be referred to as BPH, BPNH, PNH or grey matter heterotopia. PVNH can also appear in other places in the brain, for example towards the back. If you are wondering why some medical use PNH as an acronym and we don’t, this is because PNH is en entirely different rare disorder, so we stick with PVNH. Our community includes all forms of neuronal heterotopia disorders.
The incidence of PVNH is unknown because some people may not show symptoms. It is estimated that about 50% of occurences are genetically linked to the X-chromosome however, as genetic diagnoses evolve, this can vary. The other 50% are thought to be spontaneous mutations. The genetic forms of PVNH are caused by mutation or deletion of one of the following genes: FLNA, ARFGEF2, ERMARD and NEDD4L. In recent years new genes have been identified, however they may still need to be validated as a definite cause so we may not always list them until official sources do. In the last decade, chromosomal abnormalities have also been described in medical literature as causative.
For SBH (Subcortical Band Heterotopia) two genes were identified: DCX and LIS-1.
It is estimated that up to 90% of individuals affected by PVNH will have seizures. It can also cause cognitive and motor issues, cardiovascular problems, lung disorder, gastrointestinal issues and psychiatric disorder in some individuals.
Affected individuals may be asymptomyomatic or have one or many symptoms that vary from mild to severe.
There appears to be 5 different distinguisable types of periventricular nodular heterotopia:
(1) bilateral and symmetrical;
(2) bilateral single-noduled;
(3) bilateral and asymmetrical – x-linked, with a female predominance and known familial cases of epilepsy. This form of PVNH is associated with the Xq28 chromosome and caused by a mutation in the Filamin A or 1 (FLNA) gene. Recent findings have demonstrated it is also associated with X-Linked PVNH – the very form of PVNH my family is affected by. Medical reports allege that males show early lethality (in utero or soon after birth) although cases of FLNA mutations have been reported in boys (some showing mild symptoms and others very severe) and in adult men. Some are also part of our PVNH Support community!!
(4) unilateral: this form is not reported to have sex or familial prevalence it appears.
and (5) unilateral with extension to neocortex.
Again, as research identifies new forms, we will update this page.
In typical X-Linked PVNH, generally, females present with seizures which appear at the average age of 14-15 years and the disease includes an increased risk for stroke and other vascular/coagulation problems as well as pulmonary disease, although we often see in our PVNH Communiy a diverse number of individuals be diagnosed at a very young age or even later in life. Intellectual delays are sometimes present as well as motor delays or physical impairments. Again, this can vary greatly in terms of how each individual is affected.
It is important to note that people can have PVNH and have normal intelligence and live well.
It can sometimes be associated with other cortical malformations, such as Polymicrogyria (PMG).
World PVNH Disorder Awareness Day is celebrated on August 7. It was created in 2012 by Ella’s Mom and founder of PVNH Support & Awareness, Yolaine Dupont, after Ella passed away from PVNH in 2009.
To find out more about PVNH, visit the dedicated page on the Genetics Home Reference’s site (laymen’s term) or the ones on the National Center for Biotechnology Information‘ and Orpha.net sites (the laters are comprised of more technical information). You can also download our PVNH pamphlet which is updated yearly (the 2020 version is coming soon!). Do keep in mind that some of the resources we point to may not always be updated at the moment you consult them, so be sure to look at the date of the source and remember that as in all rare diseases, the process of diagnoses, research and validation of information takes time.