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OVERVIEW

Many chromosomal anomalies are associated with childhood-onset epilepsy with distinctive features. Accurate electroclinical delineation helps identify chromosomal anomalies in infants classified with cryptogenic epilepsy. Chromosomal disorders carry distinct risks of recurrence making accurate classification important for proper genetic counseling.

Chromosome anomalies may result from abnormalities in number or structure. Abnormalities of chromosome number include polyploidy and autosomal and sex chromosome aneuploidy. Aneuploidy refers primarily to "monosomy" (the presence of only one copy of a chromosome in an otherwise diploid cell) and "trisomy" (three copies of a chromosome). Abnormalities of chromosome structure consist primarily of translocations (interchange of genetic material between nonhomologous chromosomes); deletions (caused by a chromosome break and subsequent loss of genetic material); and duplications (i.e., partial trisomy of genetic material).1 The classic belief that karyotype is sufficient to rule-out chromosomal anomalies applies only to chromosomal anomalies related to number. Structural anomalies do not fit this scenario and often require more detailed investigation. Therefore, for some syndromes, it is important to first recognize the disorder clinically in order to facilitate correct genetic testing.

This chapter summarizes some of the relevant aspects of epilepsy, electroencephalography (EEG) and genetic data that may guide the identification of chromosomal disorders in early postnatal life, when the phenotype does not confer the diagnosis.

CHROMOSOME 1

1p36 DELETION

The 1p36 deletion syndrome is a disorder with multiple congenital anomalies and mental retardation characterized by growth delay, epilepsy, congenital heart defects, a characteristic facial appearance, and precocious puberty2,3 (Fig. 34–1).

Figure 34–1.

Epilepsy characterization in chromosomal disorders.

Monosomy 1p36 is a contiguous gene syndrome considered to be the most common subtelomeric microdeletion syndrome, with an estimated prevalence is 1–5.000. 1p36 deletions account for 0.5%–1.2% of idiopathic mental retardation.3

CLINICAL DIAGNOSIS

PHENOTYPE

The most common features include suggestive facial traits (epicanthus, straight eyebrows, deep-set eyes, midface hypoplasia, broad nasal root/bridge, long philtrum, and pointed chin), microbrachycepahly, large late-closing anterior fontanelle, posteriorly rotated low-set abnormal ears (Fig. 34–2). In addition, motor-delay hypotonia, moderate to severe mental retardation, growth delay, sensorineural deafness, and eye/visual abnormalities with visual inattentiveness, epilepsy, brachy/camptodactyly, and/or short fifth finger(s) are also observed. The majority of patients have heart defects, and some present with a rare congenital cardiomyopathy that results from failure of myocardial development during embryogenesis (noncompaction cardiomyopathy). Associated malformations include central nervous system (CNS) and skeletal and renal abnormalities and abnormal genitalia, Affected patients have abusive behavior, hypotonia, and developmental delay with poor or absent speech.3,4,5,6,7

Figure 34–2.

Diagnostic evaluation based on epilepsy associated to clinical findings.

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