Benign Familial Neonatal Seizures
Edit

Benign familial neonatal seizures (BFNS) is a condition characterized by recurrent seizures in newborn babies. The seizures begin around day 3 of life and usually go away within 1 to 4 months. The seizures can involve only one side of the brain (focal seizures) or both sides (generalized seizures). Many infants with this condition have generalized tonic-clonic seizures (also known as grand mal seizures). This type of seizure involves both sides of the brain and affects the entire body, causing muscle rigidity, convulsions, and loss of consciousness.

genetic conditions

1. Introduction

A test called an electroencephalogram (EEG) is used to measure the electrical activity of the brain. Abnormalities on an EEG test, measured during no seizure activity, can indicate a risk for seizures. However, infants with BFNS usually have normal EEG readings. In some affected individuals, the EEG shows a specific abnormality called the theta pointu alternant pattern. By age 2, most affected individuals who had EEG abnormalities have a normal EEG reading.

Typically, seizures are the only symptom of BFNS, and most people with this condition develop normally. However, some affected individuals develop intellectual disability that becomes noticeable in early childhood. A small percentage of people with BFNS also have a condition called myokymia, which is an involuntary rippling movement of the muscles. In addition, in about 15 percent of people with BFNS, recurrent seizures (epilepsy) will come back later in life after the seizures associated with BFNS have gone away. The age that epilepsy begins is variable.

2. Frequency

Benign familial neonatal seizures occurs in approximately 1 in 100,000 newborns.

3. Causes

Mutations in two genes, KCNQ2 and KCNQ3, have been found to cause BFNS. Mutations in the KCNQ2 gene are a much more common cause of the condition than mutations in the KCNQ3 gene.

The KCNQ2 and KCNQ3 genes provide instructions for making proteins that interact to form potassium channels. Potassium channels, which transport positively charged atoms (ions) of potassium into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals.

Channels made with the KCNQ2 and KCNQ3 proteins are active in nerve cells (neurons) in the brain, where they transport potassium ions out of cells. These channels transmit a particular type of electrical signal called the M-current, which prevents the neuron from continuing to send signals to other neurons. The M-current ensures that the neuron is not constantly active, or excitable.

Mutations in the KCNQ2 or KCNQ3 gene result in a reduced or altered M-current, which leads to excessive excitability of neurons. Seizures develop when neurons in the brain are abnormally excited. It is unclear why the seizures stop around the age of 4 months. It has been suggested that potassium channels formed from the KCNQ2 and KCNQ3 proteins play a major role in preventing excessive excitability of neurons in newborns, but other mechanisms develop during infancy.

About 70 percent of people with BFNS have a mutation in either the KCNQ2 or the KCNQ3 gene. Researchers are working to identify other gene mutations involved in this condition.

4. Inheritance

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. A few cases result from new mutations in the KCNQ2 gene. These cases occur in people with no history of benign familial neonatal seizures in their family.

5. Other Names for This Condition

  • benign familial neonatal convulsions
  • benign familial neonatal epilepsy
  • benign neonatal convulsions
  • benign neonatal epilepsy
  • BFNS

References

  1. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ,Steinlein OK. A potassium channel mutation in neonatal human epilepsy. Science.1998 Jan 16;279(5349):403-6.
  2. Castaldo P, del Giudice EM, Coppola G, Pascotto A, Annunziato L, Taglialatela M. Benign familial neonatal convulsions caused by altered gating of KCNQ2/KCNQ3potassium channels. J Neurosci. 2002 Jan 15;22(2):RC199.
  3. Chung HJ, Jan YN, Jan LY. Polarized axonal surface expression of neuronal KCNQchannels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminaldomains. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8870-5.
  4. Lerche H, Biervert C, Alekov AK, Schleithoff L, Lindner M, Klinger W,Bretschneider F, Mitrovic N, Jurkat-Rott K, Bode H, Lehmann-Horn F, Steinlein OK.A reduced K+ current due to a novel mutation in KCNQ2 causes neonatalconvulsions. Ann Neurol. 1999 Sep;46(3):305-12.
  5. Miceli F, Soldovieri MV, Joshi N, Weckhuysen S, Cooper E, Taglialatela M.KCNQ2-Related Disorders. 2010 Apr 27 [updated 2018 Sep 27]. In: Adam MP, ArdingerHH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Availablefrom http://www.ncbi.nlm.nih.gov/books/NBK32534/
  6. Rogawski MA. KCNQ2/KCNQ3 K+ channels and the molecular pathogenesis ofepilepsy: implications for therapy. Trends Neurosci. 2000 Sep;23(9):393-8.Review.
  7. Schroeder BC, Kubisch C, Stein V, Jentsch TJ. Moderate loss of function ofcyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature. 1998 Dec17;396(6712):687-90.
  8. Singh NA, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, Anderson VE,Sanguinetti MC, Leppert MF; BFNC Physician Consortium. KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of thefunctional and mutation spectrum. Brain. 2003 Dec;126(Pt 12):2726-37.
  9. Soldovieri MV, Miceli F, Bellini G, Coppola G, Pascotto A, Taglialatela M.Correlating the clinical and genetic features of benign familial neonatalseizures (BFNS) with the functional consequences of underlying mutations.Channels (Austin). 2007 Jul-Aug;1(4):228-33.
  10. Volkers L, Rook MB, Das JH, Verbeek NE, Groenewegen WA, van Kempen MJ,Lindhout D, Koeleman BP. Functional analysis of novel KCNQ2 mutations found inpatients with Benign Familial Neonatal Convulsions. Neurosci Lett. 2009 Oct2;462(1):24-9. doi: 10.1016/j.neulet.2009.06.064.
  11. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D.KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of theM-channel. Science. 1998 Dec 4;282(5395):1890-3.
More
Related Content
Neonatal intraventricular hemorrhage is a serious condition associated with significant acute and long-term morbidity and mortality. Neurosurgical intervention aims to relieve life-threatening raised intracranial pressure and prevent neurological deterioration. In recent years, advancements in disease understanding have paved the way for clinicians to re-evaluate conventional approaches in the management of affected patients. Examples include various neurosurgical techniques to actively reduce blood products with a view to avoid the consequences of complex hydrocephalus and intraparenchymal injury in the developing brain. In this entry paper, we aim to provide an overview of the current perspectives, pathophysiology and management strategies for this difficult condition.
Keywords: intraventricular hemorrhage of prematurity; neonatal intraventricular hemorrhage; post-hemorrhagic hydrocephalus
This entry reviews the health condition known as Roemheld syndrome, or gastrocardiac syndrome in modern medicine. A pathology of gastrointestinal origin, the syndrome relies on a gut–brain–heart triad, interconnected by the vagus nerve. Pressure from the intestines pushes the stomach into the diaphragm and activates the vagus nerve, which affects the heart rate and gives the perception of cardiac issues. This distressing sensation, which usually comes after meals or with other digestive problems, causes anxiety or panic. Although events not arising from anatomic abnormalities are relatively harmless, hypersensitivity to these uncomfortable sensations may precipitate psychiatric problems (anxiety or depression) that cause repeated gastrocardiac events through sympathetic activation and the disruption of peristalsis. Treatment is usually symptomatic and may include diet, lifestyle changes, probiotics, or prescriptions that increase gut motility, but this specific set of reproducible symptoms may also be caused by hiatal hernia or side effects from medication/surgery and treated with respect to those mechanical causes. This review highlights details from the most current knowledge of the condition and offers suggestions for clinical management based on the literature.
Keywords: Roemheld; gastrocardiac; IBS; SIBO; vagus
The use of antiepileptic drugs during pregnancy has always been a controversial topic. Researchers from the University of Bristol discussed the long-term safety evidence of other antiepileptic drugs during pregnancy. The results show that children exposed to valproate during pregnancy are more likely to have autism, intellectual disability, and attention deficit hyperactivity disorder (ADHD)than children who have not been exposed to antiepileptic drugs during pregnancy. Furthermore, children who were exposed to topiramate during pregnancy were 2.5 times more susceptible to being diagnosed with intellectual disability. In addition, those exposed to carbamazepine had a 1.25 times higher chance of being diagnosed with autism and a 1.30 times greater likelihood of facing an intellectual disability diagnosis. However, there was minimal indication that lamotrigine exposure during pregnancy significantly increased the risk of neurodevelopmental diagnoses in children.
Keywords: antiseizure medication; valproate; pregnancy; autism; intellectual disability; ADHD; neurodevelopmental diagnoses
Naegleria fowleri is a highly fatal brain-eating amoeba. What are the factors which contribute to its highly virulent nature?
Keywords: Naegleria fowleri; protozoa; trophozoite; infection
Background and Objectives: Wolfram syndrome type 1 (OMIM# 222300; ORPHAcode 3463) is an extremely rare autosomal recessive syndrome with a 25% recurrence risk in children. It is characterized by the presence of juvenile-onset diabetes mellitus (DM), progressive optic atrophy (OA), diabetes insipidus (DI), and sensorineural deafness (D), often referred to by the acronym DIDMOAD. It is a severe neurodegenerative disease with a life expectancy of 39 years, with death occurring due to cerebral atrophy. For a positive diagnosis, the presence of diabetes mellitus and optic nerve atrophy is sufficient. The disease occurs because of pathogenic variants in the WFS1 gene. The aim of this article is to present a case report of Wolfram Syndrome Type I, alongside a review of genetic variants, clinical manifestations, diagnosis, therapy, and long-term management. Emphasizing the importance of early diagnosis and a multidisciplinary approach, the study aims to enhance understanding and improve outcomes for patients with this complex syndrome. Materials and Methods: A case of a 28-year-old patient diagnosed with DM at the age of 6 and with progressive optic atrophy at 26 years old is presented. Molecular diagnosis revealed the presence of a heterozygous nonsense variant WFS1 c.1943G>A (p.Trp648*), and a heterozygous missense variant WFS1 c.1675G>C (p.Ala559Pro). Results: The molecular diagnosis of the patient confirmed the presence of a heterozygous nonsense variant and a heterozygous missense variant in the WFS1 gene, correlating with the clinical presentation of Wolfram syndrome type 1. Both allelic variants found in our patient have been previously described in other patients, whilst this combination has not been described before. Conclusions: This case report and review underscores the critical role of early recognition and diagnosis in Wolfram syndrome, facilitated by genetic testing. By identifying pathogenic variants in the WFS1 gene, genetic testing not only confirms diagnosis but also guides clinical management and informs genetic counseling for affected families. Timely intervention based on genetic insights can potentially reduce the progressive multisystem manifestations of the syndrome, thereby improving the quality of life and outcomes for patients.
Keywords: Wolfram syndrome type 1; optic atrophy; insulin-requiring diabetes mellitus; sensorineural deafness
Information
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
View Times: 517
Entry Collection: MedlinePlus
Revision: 1 time (View History)
Update Date: 24 Dec 2020
Video Production Service