Familial Infantile Myoclonic Epilepsy: Clinical Features in a Large Kindred with Autosomal Recessive Inheritance

Abstract

Summary:Purpose: To describe the clinical features of a large kindred with familial infantile myoclonic epilepsy (FIME) with autosomal recessive inheritance, and to discuss the nosology of the early infantile myoclonic epilepsies (IMEs).Methods: The family descends from the intermarriage of two couples of siblings. In a previous study, we mapped the genetic locus to chromosome 16p13.We analyzed results of family records and personal history, psychomotor development, neurologic examination, epilepsy features, and EEG recordings for each subject.Results: FIME has a strong penetrance (eight affected of 14 subjects) and a homogeneous clinical picture. Like the benign form of infantile myoclonic epilepsy (BIME), FIME is a true idiopathic IME with unremarkable history, no neurologic or mental impairment, good response to treatment, and normal interictal EEG pattern. Conversely, onset with generalized epileptic seizures without fever (four patients) or with fever (one patient), frequency and duration of the myoclonic seizures, occurrence of generalized tonic-clonic seizures (GTCSs) in all patients and persistence of seizures into adulthood are characteristics of the severe infantile myoclonic epilepsy (SIME).Conclusions: Clinical overlap probably exists among the myoclonic epilepsies of infancy. FIME differs from other forms of IME in its phenotypic features. The peculiar mode of inheritance is explained by the genetic background of the family. Genetic studies suggest linkage to chromosome 16 in familial cases of true IME.

Explorative two‐locus linkage analysis suggests a multiplicative interaction between the 7q32 and 16p13 myoclonic seizures‐related photosensitivity loci

“…The symptoms start in early infancy as myoclonic seizures, febrile convulsions and tonic-clonic seizures, and with frequent paroxysmal features on IPS [de Falco et al, 2001;Zara et al, 2000]. Some of these features resemble the phenotype observed in our families , suggesting that both share a susceptibility gene at this locus.…”

Homozygous TBC1D24 mutation in two siblings with familial infantile myoclonic epilepsy (FIME) and moderate intellectual disability

“…Ten years after having mapped the FIME locus to chromosome 16p13.3, mutations in the TBC1D24 gene have been found by targeted next-generation sequencing (Falace et al, 2010;de Falco et al, 2001). Despite the recognition of FIME as a specific electro-clinical entity among the classification of the International League Against Epilepsy (ILAE), other families with a similar phenotype have been rarely reported.…”

“…The detailed electroclinical presentation, reported ten years earlier, has long remained an isolated description (de Falco et al, 2001). In the past year, thanks to the use of whole-exome sequencing, additional mutations in TBC1D24 have been reported in an increasing range of developmental disorders, including epilepsy of various severity, non-syndromic deafness and DOORS syndrome (OMIM 220500) that gets its name from the acronym of the main features: deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (Corbett et al, 2010;Milh et al, 2013;Guven and Tolun, 2010;Rehman et al, 2014;Campeau et al, 2014;Stražišar et al, 2014).…”

TBC1D24truncating mutation resulting in severe neurodegeneration

“…Recessive TBC1D24 mutations were reported in two families afflicted with different diseases 3 4. An Italian family was afflicted with familial infantile myoclonic epilepsy (FIME; MIM 605021) characterised by myoclonic and generalised tonic-clonic seizures, photosensitivity, and normal neurological and mental development 3 5 6. An Arab family had focal epilepsy and intellectual disability syndrome associated with subtle cortical thickening that was most obvious in the anteromesial frontal areas.…”