An inherited atypical 1 Mb 22q11.2 deletion within the DGS/VCFS 3 Mb region in a child with obesity and aggressive behavior.

The DiGeorge, Velocardiofacial, and Conotruncal Anomaly Face syndromes (DGS/VCFS/CTAF) are knowncollectively as the 22q11.2 deletion syndrome (22q11 DS) [Shaikh et al., 2000; Swillen et al., 2000]. Although most individuals have the same large 3 Mb 22q11.2 de novo deletion, a recurrent 1.5–2 Mb proximally nested deletion is more common in familial cases of 22q11.2 DS [Iascone et al., 2002; Adeyinka et al., 2004; Fernandez et al., 2005]. Atypical smaller or uniquely placed deletions have been described in only a few patients [Kurahashi et al., 1996, 1997; Amati et al., 1999; Shaikh et al., 2000; Garcia-Minaur et al., 2002; Rauch et al., 2005]. We report on a rare 1 Mb 22q11.2 deletion in a female patient with obesity, hyperphagia, and aggressive behavior, and in her mother who had a major depressive disorder. The deletion was identified serendipitously in the proband during a microdeletion screening for syndromic obesity and was limited to the most telomeric region of the 3 Mb typically deleted region. The patient (Fig. 1) was the first child of nonconsanguinous parents with an unremarkable family history. Decreased fetal movement was reported. She was delivered at term by caesarean. Apgar scores were 8 and 9 at 1 and 5 min, respectively. The birth weight was 2.9 kg ( 25th centile), length 48 cm ( 10th centile), and the OFC 34 cm ( 25th centile). Neonatal jaundice was treated with phototherapy. The sucking reflex was present, but she fed with difficulty until 1 year of age when gastroesophageal reflux was diagnosed. Delayed closure of anterior fontanel was reported. She walked independently at 1 year and 4 months. On examination at 4 years of age, the OFC was 52 cm (50–98th centile), height was 101 cm (25–50th centile), and weight was 27 kg (>97th centile). She had a narrow forehead, synophrys, upslanted palpebral fissures, deep-set eyes, divergent strabismus of the right eye, small mouth and thin lips, high-arched palate, short philtrum, retrognathia, small hands, and pes planus. Her problems included speech articulation, sleep difficulties, hyperphagia, decreased sensitivity to pain, hyperactivity, and aggressive behavior, such as beating strangers, and self-injurious behaviors including head banging, biting, hair pulling, and skin picking. When re-evaluated at age 8 years, there were no significant changes. Compulsive food eating and behavioral problems had worsened. She weighed 67 kg (>97th centile) with truncal obesity, and height was 130 cm (50–75th centile). She took antipsychotic medication to control aggressiveness and attended a special education school. The patient’s mother has had a major depressive disorder and anxiety for 10 years, for which she has taken several psychiatric medications. She had similar facial features to her daughter including divergent strabismus on the right eye, and a hypernasal speech. She weighed 71 kg and was 160 cm tall (BMI 27.7, overweight). She was otherwise