Isodicentric Chromosome 15 Syndrome in a Korean Patient With Café-au-lait Spots

Dear Editor Isodicentric chromosome 15 [idic(15) or inv dup(15)] syndrome is a rare condition with distinctive clinical features, including developmental delay, hypotonia, epilepsy, and autism or autisticlike behavior [1]. These features can obscure a definitive diagnosis, which can only be obtained by chromosomal analysis. In a review of the types and incidence of marker chromosomes at a university hospital in Korea, there was a report on a patient that presented idic(15) along with various other marker chromosomes [2]. Recently, two additional cases of idic(15) syndrome in Korea were published in reports focusing on their specific phenotypes [3, 4]. We present a Korean patient with delayed development and café-au-lait spots, a novel associated phenotype, who was diagnosed with idic(15) syndrome. A 3-yr-old boy was referred to our hospital for evaluation of delayed development and multiple, large café-au-lait spots. He was born full term by normal vaginal delivery. The patient had no history or family history of seizure. He was a second child, and his older brother showed normal development. He showed developmental delay in speech and motor functions, which were estimated to be one year behind the reference milestones assessed by the Bayley Scales of Infant Development. Physical examination revealed multiple café-au-lait spots (3-10 cm) on the right hemitrunk, upper extremity, lower extremity, and neck (Fig. 1). Minor craniofacial dysmorphisms involving mildly deepset eyes, downslanting palpebrae, and microcephaly were also observed. Although the first impression was neurofibromatosis (NF) type 1 based on the café-au-lait spots, chromosome analysis using standard trypsin-Giemsa banding showed an abnormal karyotype 47,XY,+idic(15)(q13) (Fig. 2A). To confirm the abnormality, FISH was performed with a locus-specific identifier (LSI) probe set for SNRPN (Abbott Molecular/Vysis, Downers Grove, IL, USA), which is the causal region of Prader-Willi/Angelman syndrome. Two aqua signals and one orange signal indicated the presence of an isodicentric chromosome 15 with region q13 affected (Fig. 2B). Parental chromosome analyses were not available because of their refusal. At publication, no epileptic events had occurred, and conservative care with physical and speechlanguage therapy has been administered. Epilepsy is considered to be the most significant medical concern in patients with idic(15) syndrome. Therefore, several studies have focused on the types of seizures and treatment options [5]. It is recommended that patients with idic(15) syndrome and clinicians be aware of the increased risk for seizures, which highlights the importance of accurate diagnosis of idic(15) syndrome by medical geneticists. Another interesting clinical phenotype of idic(15) syndrome is