Dyskinesia, Familial, With Facial Myokymia

Last update 01 Nov 2024

Basic Info

Synonyms

Dyskinesia, Familial, with Facial Myokymia, FDFM, FDFM - familial dyskinesia and facial myokymia

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Introduction

A rare paroxysmal movement disorder with onset in childhood or adolescence. The disease has characteristics of paroxysmal choreiform, dystonic, and myoclonic movements involving the limbs (mostly distal upper limbs), neck and/or face, which can progressively increase in both frequency and severity until they become nearly constant. Patients may also present with delayed motor milestones, perioral and periorbital dyskinesias, dysarthria, hypotonia, and weakness.

100 Clinical Results associated with Dyskinesia, Familial, With Facial Myokymia

100 Translational Medicine associated with Dyskinesia, Familial, With Facial Myokymia

0 Patents (Medical) associated with Dyskinesia, Familial, With Facial Myokymia

Literatures (Medical) associated with Dyskinesia, Familial, With Facial Myokymia

01 Apr 2014·Annals of NeurologyQ1 · MEDICINE

Gain‐of‐function ADCY5 mutations in familial dyskinesia with facial myokymia

Q1 · MEDICINE

Article

Author: Pham, Phillip H. ; Levy, Samuel ; Bloss, Cinnamon S. ; Storm, Daniel ; Topol, Eric J. ; Bird, Thomas D. ; Swanson, Phillip D. ; Scott, Erick R. ; Schork, Nicholas J. ; Friedman, Jennifer R. ; Chan, Guy C.‐K. ; Topol, Sarah E. ; Lee, Janel K. ; Torkamani, Ali ; Hisama, Fuki M. ; Bonkowski, Emily S. ; Scott‐Van Zeeland, Ashley A. ; Chen, Qi ; Oliveira, Glenn ; Chen, Dong‐Hui ; Xu, Jian ; Zhang, Guangfa ; Raskind, Wendy H. ; Chen, Ying‐Zhang ; Carson, Andrew R.

ObjectiveTo identify the cause of childhood onset involuntary paroxysmal choreiform and dystonic movements in 2 unrelated sporadic cases and to investigate the functional effect of missense mutations in adenylyl cyclase 5 (ADCY5) in sporadic and inherited cases of autosomal dominant familial dyskinesia with facial myokymia (FDFM).MethodsWhole exome sequencing was performed on 2 parent–child trios. The effect of mutations in ADCY5 was studied by measurement of cyclic adenosine monophosphate (cAMP) accumulation under stimulatory and inhibitory conditions.ResultsThe same de novo mutation (c.1252C>T, p.R418W) in ADCY5 was found in both studied cases. An inherited missense mutation (c.2176G>A, p.A726T) in ADCY5 was previously reported in a family with FDFM. The significant phenotypic overlap with FDFM was recognized in both cases only after discovery of the molecular link. The inherited mutation in the FDFM family and the recurrent de novo mutation affect residues in different protein domains, the first cytoplasmic domain and the first membrane‐spanning domain, respectively. Functional studies revealed a statistically significant increase in β‐receptor agonist‐stimulated intracellular cAMP consistent with an increase in adenylyl cyclase activity for both mutants relative to wild‐type protein, indicative of a gain‐of‐function effect.InterpretationFDFM is likely caused by gain‐of‐function mutations in different domains of ADCY5—the first definitive link between adenylyl cyclase mutation and human disease. We have illustrated the power of hypothesis‐free exome sequencing in establishing diagnoses in rare disorders with complex and variable phenotype. Mutations in ADCY5 should be considered in patients with undiagnosed complex movement disorders even in the absence of a family history. Ann Neurol 2014;75:542–549

01 May 2012·Archives of Neurology

Autosomal Dominant Familial Dyskinesia and Facial Myokymia

Article

Author: Francesca Antonacci ; Peggy Robertson ; Hillary Lipe ; Wendy H. Raskind ; Santhosh Girirajan ; Ying Zhang Chen ; Mark Rieder ; Deborah A. Nickerson ; Thomas D. Bird ; Evan E. Eichler ; Mark M. Matsushita

BACKGROUNDFamilial dyskinesia with facial myokymia (FDFM) is an autosomal dominant disorder that is exacerbated by anxiety. In a 5-generation family of German ancestry, we previously mapped FDFM to chromosome band 3p21-3q21. The 72.5-Mb linkage region was too large for traditional positional mutation identification.OBJECTIVETo identify the gene responsible for FDFM by exome resequencing of a single affected individual.PARTICIPANTSWe performed whole exome sequencing in 1 affected individual and used a series of bioinformatic filters, including functional significance and presence in dbSNP or the 1000 Genomes Project, to reduce the number of candidate variants. Co-segregation analysis was performed in 15 additional individuals in 3 generations.MAIN OUTCOME MEASURESUnique DNA variants in the linkage region that co-segregate with FDFM.RESULTSThe exome contained 23 428 single-nucleotide variants, of which 9391 were missense, nonsense, or splice site alterations. The critical region contained 323 variants, 5 of which were not present in 1 of the sequence databases. Adenylyl cyclase 5 (ADCY5) was the only gene in which the variant (c.2176G>A) was co-transmitted perfectly with disease status and was not present in 3510 control white exomes. This residue is highly conserved, and the change is nonconservative and predicted to be damaging.CONCLUSIONSADCY5 is highly expressed in striatum. Mice deficient in Adcy5 develop a movement disorder that is worsened by stress. We conclude that FDFM likely results from a missense mutation in ADCY5. This study demonstrates the power of a single exome sequence combined with linkage information to identify causative genes for rare autosomal dominant mendelian diseases.

05 Jun 2009·American Journal of Medical Genetics Part B: Neuropsychiatric GeneticsQ3 · MEDICINE

Familial dyskinesia and facial myokymia (FDFM): Follow‐up of a large family and linkage to chromosome 3p21‐3q21

Q3 · MEDICINE

Article

Author: Jeffrey Biberston ; John Wolff ; Thomas D. Bird ; Wendy H. Raskind ; Mark Matsushita ; Hillary Lipe ; Ruben Burbank ; Beate Peter

AbstractWe previously reported a five‐generation family manifesting an autosomal dominant disorder of facial myokymia and dystonic/choreic movements (FDFM). The dyskinetic episodes are initially paroxysmal but may become constant. With increasing age they may lessen or even disappear. The previous study excluded nine candidate genes chosen for their association with myokymia or chorea and two regions containing single or clustered ion channel genes. We now report identification by whole genome linkage analysis of a broad region on chromosome 3p21‐3q21 that segregates with the disease in all 10 affected members in three generations who participated in the study. GENEHUNTER‐MODSCORE Version 2.0.1 provided a maximum multipoint LOD score of 3.099. No other disorders primarily characterized by myokymia, dystonia, or chorea are known to map to this region. Identification of additional families with FDFM may narrow the critical region and facilitate the choice of candidate genes for further analysis. © 2008 Wiley‐Liss, Inc.

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Dyskinesia, Familial, With Facial Myokymia

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