Autistic and dysmorphic features associated with a submicroscopic 2q33.3–q34 interstitial deletion detected by array comparative genomic hybridization

Recently, Bisgaard et al. [2006] detected additional chromosomal abnormalities in six patients with previously known abnormal karyotypes, such as inversions and translocations, using metaphase comparative genomic hybridization (CGH) at a resolution of 2–3 Mb. They reported previously undetected interstitial deletions with CGH in their patients including a de novo 2q33.2–q34 deletion. However, no chromosome imbalances were found using conventional cytogenetics in their six patients at the inversion or translocation breakpoints. Deletions in the long arm of chromosome 2 are relatively rare and correlate with a broad spectrum of clinical findings, including developmental delay, mental retardation, hyperactivity with autistic traits and dysmorphic features including Pierre Robin sequence, cleft palate, temporal bone abnormalities and hypoplastic lungs [Kramer et al., 2000; Houdayer et al., 2001; Van Buggenhout et al., 2005; Pescucci et al., 2007]. Approximately one-half of the reported deletions involved a chromosome segment between bands 2q24.3 and 2q31.1 [Courtens et al., 1997] or terminal 2q37.3 deletions [Kitsiou-Tzeli et al., 2007]. In 1997, Courtens et al. reported the first 2q33.3– q34 interstitial deletion in a 5-week-old boy with phenotypic findings initially suggesting Seckel syndrome (e.g., preand postnatal growth retardation, microcephaly, and muscular hypotonia). Courtens et al. [1997] summarized seven cases involving at least the 2q33.3–q34 chromosome region (i.e., largest deletion 2q33–q36). Subsequently, four other cases have been reportedwith deletions in the 2q33– q35 region [Kramer et al., 2000; Riegel et al., 2001; Pescucci et al., 2003; Bisgaard et al., 2006]. Herein, we report a second case of a de novo 2q33.3–q34deletion in a 6-year-oldmale ascertained with aCGH and referred for evaluation of a de novo balanced translocation [t(4;16)(q32.2;q24.1)]. We compared findings in our case to those reported by Courtens et al. [1997], Pescucci et al. [2003], and Bisgaard et al. [2006] involving similar 2q deletions. Our patient was born to a para 4, gravid 4, 27-yearold mother and a 43-year-old father. The mother denied alcohol or drug exposure during pregnancy. The infant was delivered at term by an uncomplicated vaginal delivery with a birth weight of 3,182 g (25th centile) and length of 50.8 cm (50th centile). The head circumference was not known. The infant was discharged with the mother at 24 hr of age. During the first year of life, the patient was hospitalized on three occasions for respiratory infections (RSV and pneumonia). Sweat chloride testing for cystic fibrosis was negative. Asthma and severe allergies were diagnosed requiring treatment with loratadine, montelukast sodium, and a budesonide inhaler. Tympanostomy tubes were placed at 6 months and again at 18 months of age for persistent otitis media. The child had extensive dental caries requiring restoration at 3.5 years of age. Developmental milestones were delayed (e.g., sitting alone at 1 year, first steps at 18–24 months and first words at 24 months). At 2 years of age the