Inverted duplicated chromosome 15 (idic (15)) is the most common of the heterogeneous group of the supernumerary marker chromosomes (SMCs). The idic (15) distinct behavior disorder has been described as autistic or autistic-like. Epilepsy represents one of the main clinical challenges in idic (15) individuals. It occurs with a wide variety of seizures, with onset between ages 6 months and 9 years. Infantile spasms associated with an hypsarrhythmic electroencephalogram (EEG) have been reported in several patients. Standard cytogenetics must be associated with fluorescent in situ hybridization (FISH) analysis, using probes both from proximal chromosome 15 and from the Prader-Willi syndrome/Angelman syndrome (PWS/AS) critical region. Although brain neuroimaging (CT/MRI) is reportedly normal in most idic (15) individuals brain MRI should be performed in all those having seizures, since a malformation of the cerebral cortex may modify prognosis and management. Regular follow-up of the seizure status and pharmacotherapy is essential.

Genetic studies of the epilepsies involve two main aspects: detailed gathering of data and data analysis. The contribution of genetics to nosology and classification of the epilepsies should be carefully considered. If genetic criteria were prominent, epilepsy syndromes having heterogeneous clinical expressions would be classified within the same category and homogeneous syndromes caused by different genetic mechanisms would fall in different subcategories. The idiopathic generalized epilepsies constitute a group of syndromes characterized by absence seizures, myoclonus, and generalized tonic-clonic seizures. Chromosomal abnormalities are relatively common genetically determined conditions that increase the risk of epilepsy. Ethical and societal considerations are important in establishing guidelines for both genetic counseling and genetic research in the epilepsies. Standard karyotype and high-resolution chromosome analysis, fluorescent in situ hybridization (FISH), molecular karyotyping with array comparative genomic hybridization, multiple ligation-probe amplification (MLPA) and single-nucleotide polymorphism arrays (SNPs) are the standard cytogenetic and molecular techniques for diagnosis.

Couples referred for preimplantation genetic diagnosis (PGD) are known to be at genetic risk due to an affected family member or the birth of an affected child. PGD involves three stages: IVF, embryo biopsy and single cell diagnosis. Polymerase chain reaction (PCR) is used for the diagnosis of single gene defects such as cystic fibrosis, screening of specific diagnosis of X-linked diseases and the triplet repeats disorders such as myotonic dystrophy. For PGD patients, especially those carrying fragile X syndrome, a test of ovarian reserve is recommended. The embryo biopsies discussed in this chapter are: polar body biopsy, cleavage stage biopsy, blastocyst biopsy. The chapter lists out single gene disorders for which successful PGD protocols have been reported. Fluorescent in situ hybridization (FISH) determines the number of copies of a particular chromosome or region of a chromosome when it is difficult or impossible to obtain good quality metaphase preparations.