The duplication/inversion 15q11 or isodicentric 15 chromosome (inv dup(15) or idic(15)) syndrome is a chromosomal disorder with distinctive clinical findings characterized by early central hypotonia, developmental delay and intellectual deficit, epilepsy, and autistic behavior. Incidence at birth is estimated at 1 in 30,000 with a sex ratio of almost 1:1. Developmental delay and intellectual deficit affect all individuals with inv dup(15)/idic(15) and are usually moderate to profound. Expressive language is absent or very poor and often echolalic. Comprehension is very limited and contextual. Intention to communicate is absent or very limited. The distinct behavioral disorder manifesting in children and adolescents has been widely described as autistic or autistic-like. Epilepsy, with a wide variety of seizure types, can occur in these individuals, with onset between 6 months and 9 years. Various EEG abnormalities have been described. Muscle hypotonia is observed in almost all individuals, associated, in most cases, with joint hyperextensibility and drooling. Facial dysmorphism is absent or subtle, and major malformations are rare. Feeding difficulties are reported in the newborn period. Chromosome region 15q11q13, known for its instability, is highly susceptible to clinically relevant genomic rearrangements, such as supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15) results in tetrasomy 15p and partial tetrasomy 15q. Large rearrangements, containing the Prader-Willi/Angelman syndrome critical region (PWS/ASCR), are responsible for the inv dup(15)/idic(15) phenotype. Diagnosis is established by standard cytogenetic and FISH analysis, using probes both from proximal chromosome 15 and from the PWS/ASCR. Microsatellite analysis on parental DNA or methylation analysis on the proband DNA are also needed to detect the parent-of-origin of the inv dup(15) chromosome. Array CGH has been shown to be a powerful approach for identifying and detecting the extent of the duplication. The possible occurrence of double supernumerary isodicentric chromosomes derived from chromosome 15, resulting in partial hexasomy of the maternally inherited PWS/ASCR, should be considered in the differential diagnosis. Genetic counseling may be proposed but large rearrangements involving the PWS/ASCR and idic(15) are nearly always sporadic. Antenatal diagnosis is possible. Management of inv dup(15)/idic(15) includes a comprehensive neurophysiologic and developmental evaluation. Life expectancy is not significantly reduced.
Last update: November 2008