Reciprocal Deletion and Duplication of 17p11.2-11.2: Korean Patients with Smith-Magenis Syndrome and Potocki-Lupski Syndrome
A 17-yr-old boy revisited the hospital for rehabilitation and was referred to our genetic clinic for an evaluation of unexplained intellectual disability and language disability on July 11th, 2011. He had been delivered at week 36 of gestation by vaginal delivery after an induced preterm birth due to preeclampsia and intrauterine growth retardation. His birth weight was 1,500 g (< 3rd percentile). He spent about 25 days in the neonatal intensive care unit (NICU) for very low birth weight. The mother and father were both 33 yr old. He had an older healthy brother. The family had no history of neurologic disease or developmental delay. His parents reported that he was rather slow to walk (18 months). He had obvious language development after 3 yr old. He showed no autistic features, sleep problems, hyperactivity, or oppositional behaviors. He had two provoked seizures; his first seizure at the age of 3.5 yr was associated with hypoglycemia (serum glucose 38 mg/dL) and his second seizure occurred at the age of 7 yr during a high fever.\nOn physical examination at 17 yr, he showed no definite dysmorphic facial features or other significant findings. His dominant hand was left. His heart sound was normal without murmurs. No skeletal abnormalities were noted. His neurologic examination was normal.\nHis first neurodevelopmental evaluation was checked at age 3.5 yr. At that time (3.5 yr old), he showed mild intellectual disability, a low level of adaptive behaviors, and significant developmental language delay; his ADL functional age was 33.6 months, his fine motor functional age was 30.07 months, his cognitive functional age was 21.44 months on the DARBAS, his receptive language age was 24 months, and his expressive language age was 18-24 months on the PRES. He underwent a second neurodevelopmental evaluation at age 17 yr. His intellectual functioning was measured by the Korean Wechsler Adult Intelligence Scale (K-WAIS). He had a moderate intellectual disability; FSIQ, VIQ, and PIQ were all below 45. His social maturation quotient (SQ 48.7) also showed a moderate trainable intellectual disability. He still exhibited developmental language delay, with a receptive language age of 5 yr and an expressive language age of around 3 yr.\nLaboratory tests, which included a complete blood count, chemistry panel, lipid profile, thyroid function test, and urinalysis, were all normal. Brain MRI showed no focal lesion and a normal ventricular size (17 yr old).\nHe underwent a chromosome analysis at another hospital. The result of a blood lymphocyte karyotype was 46, XY. We performed whole genome array CGH (MACArray Karyo 1440 BAC-chip, Macrogen, Seoul, Korea), which revealed a duplication on chromosome 17p11.2 including the RAI1 gene region [arr 17p11.2 (17,575,978-19,654,341) × 3] (). The size was estimated at approximately 2.1 Mb with 4 probes that contained 11 RefSeq genes: RAI1 [MIM 607642], SMCR5, SREBF1 [MIM 184756], MIR33B [MIM 613486], TOM1L2, TRIM16L, FBXW10 [MIM 611679], FAM18B, ALDH3A2 [MIM 609523], SLC47A [MIM 609833], and ALDH3A1 [MIM 100660].