Reciprocal Deletion and Duplication of 17p11.2-11.2: Korean Patients with Smith-Magenis Syndrome and Potocki-Lupski Syndrome
A 2.9-yr-old boy visited our clinical geneticist with developmental language delay on February 23th, 2012. He was born at week 41 of gestation age by spontaneous vaginal delivery after an unremarkable pregnancy as the first child of healthy non-consanguineous Korean parents. His birth weight was 2,960 g (10-25th percentile), birth length 51 cm (50-75th percentile), and head circumference was 32 cm (3-10th percentile). The mother and father were, respectively, 28 and 31 yr old. The family had no history of neurologic disease or developmental delay. No feeding difficulties or hypotonia occurred during early infancy. He showed normal development until the age of 3-4 months. His mother reported that his development seemed to be delayed since the age of 12 months. He walked independently at 18 months. He did not speak his first words until he was 12 months old. He showed no autistic features or sleep problems. He was unable to adapt to socially acceptable behavior at kindergarten. He showed aggressive behavior and picked on his friends. There was no history of seizure at the moment.\nWhen he visited our clinic as a 2.9-yr-old, his body weight was 12.3 kg (-1.05, standard deviation score, SDS), height was 87.8 cm (-1.16 SDS), body mass index (BMI) was 15.96 kg/m2 (-0.62 SDS), and head circumference was 50 cm (-1.19 SDS). On examination, he was noted to have a broad forehead, brachycephaly, and downturned upper lip but had no dysmorphic features or other significant findings (). Eye examination was normal. His oral cavity and oropharynx were unremarkable. Extremities showed shortness of the fingers (). He was alert and made good eye contact. The other neurologic examination was normal.\nHe underwent a neurodevelopmental evaluation at 3 yr of age. He exhibited inattentive and uncooperative behavior during the tests. He revealed the cognitive function of an 18-month-old on Bayley Scales of Infant Development II. His social quotient (SQ) was 60.6 on social maturity scale (SMS). He revealed developmental language delay determined by the sequenced language scale of infants (SELSI); expressive language function was at the level of an 18-month-old, and receptive language function was at the 12-month-old level. Adaptive skill was checked with the Developmental Age Referenced Breakdown Assessment Schedules (DARBAS). He showed a lower level of adaptive behaviors; he had the activities of daily living (ADL) functional age of a 19-month-old, fine motor functional age of a 20-month-old, and a cognitive functional age of 16.6 months.\nHis hearing test (otoacoustic emissions test) was normal. The laboratory tests including complete blood count, chemistry panel, lipid profile, thyroid function test, and urinalysis were all normal. Electrocardiography and chest radiograph were normal. Brain magnetic resonance imaging (MRI) was normal, without ventriculomegaly.\nChromosome analysis revealed a deletion within the short arm of chromosome 7, with breakpoints of p11.2 and p11.2 at least 550-band resolution (). We conducted whole genome array comparative genomic hybridization (array CGH) using commercially available array-CGH slides (MACArray Karyo 1440 BAC-chip, Macrogen, Seoul, Korea) to confirm the suspected cytogenetic findings. We found a 2.6 Mb deletion on chromosome 17p11.2 (). The start and stop points of this deletion were estimated at 17,083,225 and 19,654,341 (GRCh37 February 2009 assembly) with a total of 5 probes: BAC90_H16, BAC-249_G12, BAC41_D18, BAC132_L20, and BAC10_I20. The 2.57 Mb region contained 15 RefSeq (NCBI reference sequence) genes: MPRIP [MIM 612935], PLD6, FLCN [MIM 607273], COPS3 [MIM 604665], 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].