Encyclopedia
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a disorder that causes progressive dysfunction of the brain (encephalopathy).
- genetic conditions
1. Introduction
FENIB is characterized by a loss of intellectual functioning (dementia) and seizures. At first, affected individuals may have difficulty sustaining attention and concentrating. They may experience repetitive thoughts, speech, or movements. As the condition progresses, their personality changes and judgment, insight, and memory become impaired. Affected people lose the ability to perform the activities of daily living, and most eventually require comprehensive care.
The signs and symptoms of FENIB vary in their severity and age of onset. In severe cases, the condition causes seizures and episodes of sudden, involuntary muscle jerking or twitching (myoclonus) in addition to dementia. These signs can appear as early as a person's teens. Less severe cases are characterized by a progressive decline in intellectual functioning beginning in a person's forties or fifties.
2. Frequency
This condition appears to be rare; only a few affected individuals have been reported worldwide.
3. Causes
FENIB results from mutations in the SERPINI1 gene. This gene provides instructions for making a protein called neuroserpin, which is found in nerve cells (neurons). Neuroserpin plays a role in the development and function of the nervous system. This protein helps control the growth of neurons and their connections with one another, which suggests that it may be important for learning and memory.
Mutations in the SERPINI1 gene result in the production of an abnormally shaped, unstable form of neuroserpin. Within neurons, defective neuroserpin proteins can attach to one another and form clumps called neuroserpin inclusion bodies or Collins bodies. These clumps disrupt the cells' normal functioning and ultimately lead to cell death. The gradual loss of neurons in certain parts of the brain causes progressive dementia. Researchers believe that a buildup of related, potentially toxic substances in neurons may also contribute to the signs and symptoms of this condition.
4. Inheritance
FENIB 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 many cases, an affected person has a parent with the condition.
5. Other Names for This Condition
- familial dementia with neuroserpin inclusion bodies
- FENIB
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/familial-encephalopathy-with-neuroserpin-inclusion-bodies
References
- Bradshaw CB, Davis RL, Shrimpton AE, Holohan PD, Rea CB, Fieglin D, Kent P,Collins GH. Cognitive deficits associated with a recently reported familialneurodegenerative disease: familial encephalopathy with neuroserpin inclusionbodies. Arch Neurol. 2001 Sep;58(9):1429-34.
- Coutelier M, Andries S, Ghariani S, Dan B, Duyckaerts C, van Rijckevorsel K,Raftopoulos C, Deconinck N, Sonderegger P, Scaravilli F, Vikkula M, Godfraind C. Neuroserpin mutation causes electrical status epilepticus of slow-wave sleep.Neurology. 2008 Jul 1;71(1):64-6. doi: 10.1212/01.wnl.0000316306.08751.28.
- Davis RL, Holohan PD, Shrimpton AE, Tatum AH, Daucher J, Collins GH, Todd R,Bradshaw C, Kent P, Feiglin D, Rosenbaum A, Yerby MS, Shaw CM, Lacbawan F,Lawrence DA. Familial encephalopathy with neuroserpin inclusion bodies. Am JPathol. 1999 Dec;155(6):1901-13.
- Davis RL, Shrimpton AE, Carrell RW, Lomas DA, Gerhard L, Baumann B, LawrenceDA, Yepes M, Kim TS, Ghetti B, Piccardo P, Takao M, Lacbawan F, Muenke M, Sifers RN, Bradshaw CB, Kent PF, Collins GH, Larocca D, Holohan PD. Association between conformational mutations in neuroserpin and onset and severity of dementia.Lancet. 2002 Jun 29;359(9325):2242-7. Erratum in: Lancet 2002 Oct5;360(9339):1102.
- Davis RL, Shrimpton AE, Holohan PD, Bradshaw C, Feiglin D, Collins GH,Sonderegger P, Kinter J, Becker LM, Lacbawan F, Krasnewich D, Muenke M, Lawrence DA, Yerby MS, Shaw CM, Gooptu B, Elliott PR, Finch JT, Carrell RW, Lomas DA.Familial dementia caused by polymerization of mutant neuroserpin. Nature. 1999Sep 23;401(6751):376-9.
- Galliciotti G, Sonderegger P. Neuroserpin. Front Biosci. 2006 Jan 1;11:33-45. Review.
- Gourfinkel-An I, Duyckaerts C, Camuzat A, Meyrignac C, Sonderegger P, BaulacM, Brice A. Clinical and neuropathologic study of a French family with a mutationin the neuroserpin gene. Neurology. 2007 Jul 3;69(1):79-83.
- Miranda E, MacLeod I, Davies MJ, Pérez J, Römisch K, Crowther DC, Lomas DA.The intracellular accumulation of polymeric neuroserpin explains the severity of the dementia FENIB. Hum Mol Genet. 2008 Jun 1;17(11):1527-39. doi:10.1093/hmg/ddn041.
- Yepes M, Lawrence DA. Neuroserpin: a selective inhibitor of tissue-typeplasminogen activator in the central nervous system. Thromb Haemost. 2004Mar;91(3):457-64. Review.
