Benign Infantile Convulsions Research Articles

Paroxysmal dyskinesias as a paradigm of paroxysmal movement disorders.

Paroxysmal dyskinesias are genetically and clinically heterogeneous. Paroxysmal kinesigenic choreoathetosis is frequently familial, with autosomal-dominant transmission. Benign infantile convulsions can be observed in these families and both diseases as linked to the pericentromeric region of chromosome 16. Two different forms of paroxysmal dystonic choreoathetosis are distinguished on clinical grounds, by the presence or absence of spasticity, and genetically, as they are linked with loci on different chromosomes. Among the paroxysmal disorders, these diseases may belong to the group of channelopathies.

Paroxysmal Kinesigenic Choreoathetosis Locus Maps to Chromosome 16p11.2-q12.1

Paroxysmal kinesigenic choreoathetosis (PKC), the most frequently described type of paroxysmal dyskinesia, is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To localize the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC. Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination fraction [theta] =.00; penetrance [p] =.7) at marker D16S3081, and a maximum multipoint LOD score for a subset of markers was calculated to be 11.51 (p = 0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of approximately 12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16q12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for "infantile convulsions and paroxysmal choreoathetosis" (MIM 602066), a recently recognized clinical entity with benign infantile convulsions and nonkinesigenic paroxysmal dyskinesias.

Epilepsy and paroxysmal movement disorders in families: evidence for shared mechanisms

ABSTRACT The epilepsies have been regarded as clinically distinct from the paroxysmal movement disorders. Recently, a variety of ion channel defects have been identified as the biological basis of certain familial epilepsies and paroxysmal movement disorders. We studied two families with the cooccurrence of epilepsy, movement disorders and migraine. Information was obtained on 147 individuals in the two families. In family WF, there was a co‐occurrence of epilepsy (benign infantile convulsions, idiopathic generalized epilepsy), episodic ataxia (with cerebellar atrophy and without myokymia) and common migraine. In family CL, epilepsy (febrile seizures, febrile seizures plus), kinesigenic paroxysmal dyskinesia and migraine (including hemiplegic migraine) were observed in various combinations over 3 generations. The observations in these two families, together with review of the literature, suggest that the co‐occurrence of epilepsy (particularly benign infantile convulsions), paroxysmal movement disorders and migraine is not due to chance. Thus, these distinct clinical phenomena could have a shared biological basis and ion channel defects are an attractive possibility.

Genetics of Familial Infantile Convulsions

Four families from northwestern France with autosomal dominant benign infantile convulsions and paroxysmal choreoathetosis were studied genetically by linkage analysis at the Wellcome Trust Centre for Human Genetics, University of Oxford, UK, and at Genetic Clinics in Amiens, France.

Familial Infantile Convulsions and Paroxysmal Choreoathetosis: A New Neurological Syndrome Linked to the Pericentromeric Region of Human Chromosome 16

Benign infantile familial convulsions is an autosomal dominant disorder characterized by nonfebrile seizures, with the first attack occurring at age 3-12 mo. It is one of the rare forms of epilepsy that are inherited as monogenic Mendelian traits, thus providing a powerful tool for mapping genes involved in epileptic syndromes. Paroxysmal choreoathetosis is an involuntary-movement disorder characterized by attacks that occur spontaneously or are induced by a variety of stimuli. Classification is still elusive, and the epileptic nature of this movement disorder has long been discussed and remains controversial. We have studied four families from northwestern France in which benign infantile convulsions was inherited as an autosomal dominant trait together with variably expressed paroxysmal choreoathetosis. The human genome was screened with microsatellite markers regularly spaced, and strong evidence of linkage for the disease gene was obtained in the pericentromeric region of chromosome 16, with a maximum two-point LOD score, for D16S3133, of 6.76 at a recombination fraction of 0. Critical recombinants narrowed the region of interest to a 10-cM interval around the centromere. Our study provides the first genetic evidence for a common basis of convulsive and choreoathetotic disorders and will help in the understanding and classification of paroxysmal neurological syndromes.

Partial cosegregation of familial hemiplegic migraine and a benign familial infantile epileptic syndrome.

We studied a large Dutch-Canadian family, in which two very rare hereditary paroxysmal neurologic disorders, familial hemiplegic migraine (FHM) and a "benign familial infantile epileptic syndrome" concur and partially cosegregate. FHM is a dominantly inherited subtype of migraine with attacks of hemiparesis, linked to chromosome 19p13 in 50% of the families tested. Recently mutations in a brain-specific P/Q-type Ca2+ channel alpha1 subunit gene (CACNL1A4) were identified in families with chromosome 19-linked FHM. The infantile epileptic syndrome resembles to two other dominantly inherited benign epilepsies occurring in the first year of life, benign familial neonatal convulsions (BFNC), assigned to chromosomes 20q13.2 and 8q, and benign infantile familial convulsions (BIFC), as yet unlinked. Linkage analysis was performed for the known locations of FHM and BFNC. The question whether the two conditions in this family can be caused by a single gene defect was addressed by additional linkage analysis. We excluded linkage of the infantile convulsions to markers on chromosome 20q13.2, 8q, or 19p13. This indicates the existence of a third locus for benign familial convulsions in the first year of life. Linkage of FHM to these markers was not formally excluded but seems very unlikely. Statistical analysis of whether, in this family, both conditions are caused by a single gene defect was inconclusive. We describe a "benign familial infantile epileptic syndrome" with attacks of FHM at a later age. Further genetic studies in this family may help to unravel the genetic basis of epilepsy or migraine or both.

Clinical analysis of 22 infants with afebrile cluster seizures.

The inclusion criteria for afebrile cluster seizures in infancy are defined as follows: (1) frequency of afebrile seizures at least 2 episodes within 72 hours; (2) seizure onset between 2 months and 3 years of age; (3) excluding febrile convulsion, central nervous system infections, status epilepticus, well-known epileptic syndromes in infancy (e.g. early myoclonic encephalopathy, early infantile epileptic encephalopathy, benign myoclonic epilepsy, infantile spasms. Lennox-Gastaut syndrome), electrolyte imbalance, watery diarrhea, head injury and intoxication. From 1986 to 1996, retrospectively and prospectively 22 patients were collected who fulfilled the above criteria. Based on whether or not a strong family history was present and a history of mild diarrhea was associated with seizure onset, they were divided into three groups: Group I, benign infantile familial convulsions (4 patients); Group II, cluster seizures with mild diarrhea in infancy (5 patients); Group III, cluster seizures without diarrhea in infancy (13 patients). Before seizure onset and during follow-up, all of the patients had normal development. The seizure pattern in all was generalized, most tonic type with duration of seizure less than five minutes in the majority. Recurrence rate was 100% in Group I and no recurrence in Group II. In 16 patients who were seizure-free over 12 months, the duration of persistence varied from 1 day to 8 months, and was shortest in Group II (range, 1 to 3 days). It was concluded that the vast majority of afebrile cluster seizures in infancy are benign in nature. Whether anticonvulsant therapy is justified must be individualized.

Evaluation of febrile convulsions observed in patients with benign infantile convulsions and their families

Evaluation of febrile convulsions observed in patients with benign infantile convulsions and their families

Epileptic Syndromes in Infancy and Childhood: Recent Advances

Epileptic syndromes are more reliable than etiology in determining prognosis and optimal treatment in infants and children. Benign neonatal and infantile convulsions are either idiopathic or dominantly inherited, the latter being genetically nonallelic. Forms of idiopathic generalized epilepsy (IGE) include absence epilepsy, benign myoclonic epilepsy of infancy, and epilepsy with generalized myoclonic atonic seizures. Forms of idiopathic partial epilepsy include benign partial epilepsy with centrotemporal spikes (BECT), benign partial epilepsy with occipital paroxysms, idiopathic partial epilepsy with affective seizures, and benign partial epilepsies with extreme somatosensory evoked potentials (SEPS). These idiopathic epilepsies appear to result from a multifactorial genetic predisposition. The diagnosis is based on strict clinical and EEG criteria. In epileptogenic encephalopathies, cognitive disorders are the main feature and are linked to so-called interictal abnormalities. Some epileptic syndromes, particularly myoclonic epilepsies, remain unclassifiable because of poor understanding of nosology or heterogeneous outcome.

Benign infantile familial convulsions: Clinical and genetic aspects

Benign infantile familial convulsions: Clinical and genetic aspects

Benign Familial Convulsions

Results of linkage analysis between benign infantile familial convulsions (BIFC) and two linked DNA markers, D20S19 and D20S20, in 52 members from eight BIFC pedigrees are reported from centers in Montpellier and Paris, France, and Rome and Treviso, Italy.

Benign infantile familial convulsions are not an allelic form of the benign familial neonatal convulsions gene

Benign infantile familial convulsions (BIFC) and benign familial neonatal convulsions (BFNC) are two forms of familial convulsions having an age of onset within the first year of life. The gene responsible for BFNC has been mapped to chromosome 20q in the close vicinity of D20S19 and D20S20 markers. We performed linkage analysis between BIFC and D20S19-D20S20 in eight families in order to know whether the BFNC gene is also implicated in BIFC. Several apparent obligate crossovers between affected members were detected. The data here presented demonstrate that the BFNC gene is not responsible for BIFC.

Long-term prognosis of convulsive disorders in the first year of life: mental and physical development and seizure persistence.

A follow-up study was made on 304 children (164 boys, 140 girls) with convulsive disorders, excluding occasional convulsions, in the first year of life. All patients except 45 who died were followed until 6 years of age or older. At the final follow-up, the subjects were divided into six groups according to the degree of mental and physical development (groups I-VI). Seizures were regarded as absent if the patient had been seizure free for more than 3 years. At the final follow-up, seizures had ceased in 57.7%, and 43.4% had normal mental and physical development (group I). As to the initial diagnosis, the percentage of group I at the final follow-up was 81.8% with febrile convulsions and 37.6% with epilepsy. In patients without seizures it was 69.7% with febrile convulsions and 55.8% with epilepsy. Some 80.6% of patients with unclassified generalized motor seizures, 11.5% of those with infantile spasms, 2.9% of those with secondary generalized epilepsy other than infantile spasms, 46.4% of those with partial seizures, and 25.0% of those with hemiconvulsive seizures were finally placed in group I. The percentage of patients without seizures was 81.4, 33.0, 34.4, 57.7, and 100%, respectively. As has been suggested, among the first-year epilepsies, a subgroup with a more favorable prognosis may exist. Further studies regarding the etiology, ictal EEGs, and effectiveness of treatment and long-term prognosis of these cryptogenic benign infantile convulsions are needed to provide a firm basis for understanding convulsive disorders in the first year of life.

Etiology of convulsions in neonatal and infantile period.

1) Etiology of convulsions starting prior to two years of age was discussed in 418 cases. Neonatal seizures before 30 days old appeared in 86 cases (53 boys and 33 girls). Three hundred and thirty-two patients (172 boys and 160 girls) had convulsions in infancy. Twelve patients (9 boys and 3 girls) suffered from convulsions both in neonatal and infantile period. 2)Etiology of convulsions was prenatal in 67 cases (16%), natal in 49 cases (12%), postnatal in 158 cases (38%) and unknown in 144 cases (34%). Prenatal factors consisted of cerebral malformation (23 cases, 6%), associated physical minor anomaly such as cataracta or finger abomaly (11 cases, 3%), abnormal pernatal history (8 cases, 2%), congenital heart disease 3) cases, 1%), tuberose scleorsis (7 cases, 2%) and positive family history (13 cases, 3%). Postnatal causes included hypocalcemia or hypoglycemia (7 cases, 2%), brain tumors (3 cases, 1%), breath-holding spells (21 cases, 5%), febrile convulsion (44 cases, 11%), bathing (3 cases, 1%), afebrile colds (3 cases, 1%), purulent meningitis (17 cases, 4%), DPT immunization (10 cases 2%), vaccination (7 cases, 2%) and acute hemiplegia (10 cases, 2%). The group of unknown etiology were as fns (38 cases, 9%), epilepsy associated with interictal signs (23 cases, 6%), benign infantile convulsions (57 cases, 14%), neonatal convulsion of unknown etiology (12 cases, 3%) and miscellaneous categories (4%). 3) Pregnancy was abnormal in 53% of cases with cerebral malformation. Asphyxia at birth was noted in 43% of patients with tuberose sclerosis and in 35% of congenital cerebral abomaly. 4) Pneumoencephalographic examinations revealed midline anomaly in 50% of cerebral malformation. It was abnormal in all cases with tuberose sclerosis, head injury and epilepsy with interseizure neurological signs. 5) There were no correlations between the seizure pattern and the etiology in neonatal convulsion. In infancy, focal-unilateral convulsions and infantile spasms were frequently associated with organic damages. Generalized seizures were seen in organic lesions as well as functional ones although approximately half of the cases were febrile convulsion, benign infantile convulsion or breath-holding spell. 6) EEG features of cerebral malformation were asymmetrical or multifocal dischages in neonatal period and hypsarhythmia or focal-unilateral spike discharges in infancy. Tuberose sclerosis showed hypsarhythmia in infancy. In birth injury or cerebral anoxia, EEG mostly revealed focal-unilateral abnormality or suppression-burst activity in newborns and hypsarhythmia or focal features in infants. 7) The occurrence rate of neonatal seizures in autopsy cases with intracranial pathology was demonstrated. EEG with intravenous diazepam was useful to know pathophysiology of infantile spasms.