Elsevier

Brain and Development

Volume 22, Issue 7, October 2000, Pages 432-435
Brain and Development

Original article
Co-segregation of benign infantile convulsions and paroxysmal kinesigenic choreoathetosis

https://doi.org/10.1016/S0387-7604(00)00178-9Get rights and content

Abstract

We report seven families and two sporadic cases in which benign infantile convulsions and paroxysmal kinesigenic choreoathetosis were co-segregated. Clinical investigations included physical and neurological examinations, blood electrolyte values, interictal and ictal electroencephalograms, and computed tomography or magnetic resonance imaging of the brain. The family pedigree was confirmed and the clinical history of the relatives was obtained. Seventeen individuals developed infantile convulsions followed by paroxysmal dyskinesias during childhood or adolescence. Six had only infantile convulsions, and two had only paroxysmal dyskinesias. The seizures never persisted into childhood or recurred in adulthood. The seizure type was a complex partial seizure, with or without secondary generalization, in nine of 14 patients. Paroxysmal dyskinesias, a subgroup of paroxysmal kinesigenic choreoathetosis, occurred for less than 5 min. The attacks of dyskinesias began at age 5–12 years in most patients, and tended to remit in adulthood. The mode of inheritance was apparently autosomal dominant in four of the families (17 affected individuals), who were diagnosed with ICCA syndrome (infantile convulsions and paroxysmal choreoathetosis). However, the condition occurred only among siblings in three families (six patients), and sporadically in two patients, suggesting genetic heterogeneity in this distinct co-segregation.

Introduction

Paroxysmal dyskinesias (PDs) are a group of heterogeneous neurological disorders, characterized by attacks of involuntary movements. Some PDs are definitely of genetic origin, and some of their genes have been mapped. The first gene for paroxysmal dystonic choreoathetosis was located on chromosome 2q [1], [2], and a subsequent gene for paroxysmal choreoathetosis/spasticity was mapped on chromosome 1p, around where the potassium channel genes are clustered [3].

Szepetowski et al. recently located a third PD gene on the pericentromeric region of chromosome 16 [4]. The gene is linked to a new neurological syndrome with autosomal dominant inheritance (infantile convulsions and choreoathetosis, ICCA). The syndrome consists of two distinct paroxysmal disorders. One is seizures occurring at age 3–12 months with a favorable outcome, and the other is paroxysmal dyskinesias occurring later in childhood or adolescence.

Paroxysmal kinesigenic choreoathetosis (PKC) was then mapped to the same pericentromeric region of chromosome 16 [5]. The locus may be that of ICCA syndrome itself, since 18 of the 43 patients with PKC (six in eight families) also had a history of afebrile convulsions in infancy.

Benign infantile convulsions (BIC) are a common seizure disorder occurring in neurodevelopmentally normal infants [6], [7], [8]. This syndrome is probably genetically heterogenous, despite a high familial predisposition. The gene locus was located on chromosome 19 in families with an autosomal dominant trait [9].

We describe 25 individuals in whom BIC and PKC were closely associated. The clinical presentation of the two paroxysmal disorders was homogenous. Recognition of this condition is important for an excellent prognosis. Anticonvulsants, especially carbamazepine, are efficacious against both BIC and PKC [6], [7], [10].

Section snippets

Patients and Methods

The propositi and their siblings were evaluated, diagnosed and treated by pediatric neurologists (H.H., T.F., H.N., Y.H., M.T., Y.H.). Clinical investigations included physical and neurological examinations, blood electrolyte values, interictal and ictal electroencephalograms, and computed tomography or magnetic resonance imaging of the brain. The family pedigree was ascertained and the clinical history of the relatives was obtained. Some of the relatives were also examined.

A seizure disorder

Results

Fig. 1 shows the pedigrees of seven families and two sporadic cases. All were Japanese. Individuals were considered affected if they had either BIC, PKC or both. Four families had affected members in two or more generations (families A–D). Three families had two patients each in a single generation (families E–G). Two cases occurred sporadically (families H and I).

Table 1 depicts the clinical profiles of the 25 affected individuals. A total of 23 patients experienced BIC (17 had both BIC and

Discussion

We identified seven families (23 affected individuals) and two sporadic cases in whom BIC and PKC were associated. This co-segregation with an autosomal dominant trait (Families A, B, C and D) is identical to ICCA syndrome [4]. This syndrome was first delineated in four French families, and was later confirmed in a Chinese family [12]. An addition of four Japanese families confirms that this syndrome is distributed among different ethnic groups. The association of infantile convulsions and PKC

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      In a recent study a copy number variation at human chromosome 16p11 has been associated with ICCA syndrome.19 After ICCA was recognized as a new syndrome, other descriptions of the association between BIS and PD have been reported.20–30 To date, no ICCA gene has been discovered.

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