The variable expression of the chromosome 22q11.2 deletion: Findings in 216 patients

We have enrolled 216 individuals with a chromosome 22qll.2 deletion diagnosed using fluorescence in situ hybridisation in a prospective multidisciplinary study. Seventy-five percent of patients were ascertained at The Children's Hospital of Philadelphia and 25% were self-selected individuals who sought care at our institution following the diagnosis of a 22qll.2 deletion. Approximately 10% of cases were familial where the parent was ascertained following the diagnosis of their child. Fifty-two percent of patients were female and forty-eight percent were male. Eighty percent of the patients in the study were Caucasian. Whereas, only 13% of patients were African-American. Fifty-seven percent of patients were 5 years of age or younger. Fifty-eight percent of patients were ascertained through genetics, 27% from cardiology, 10% from the cleft palate team including the speech pathologist and ENT, 3% from Neurology and Child Development and 2% from Immunology and Rheumatology. Depending on the age and presenting problems of the child, the multidisciplinary evaluation generally included the following: genetics, plastic surgery, speech pathology, otolaryngology, audiology. dental, cardiology, immunology, child development, child psychology, neurology, and general paediatrics. Some patients also required evaluation by: the feeding team, endocrinology, rheumatology, gastroenterology, neurosurgery, general surgery, orthopaedics, urology, haematology. psychiatry, and ophthalmology. Laboratory studies, in addition to FISH studies in the patient and parents, often included: renal ultrasound, an immune profile, electrocardiogram, echocardiogram. Of this group 33.3% demonstrated significant delays in development. 33.3% were mildly delayed, and 33.3% functioned in the average range. Emergence of language skills were delayed in all children. In the preschool population, there was a striking prevalence of children over age 24 months who were not yet speaking at all or who had just a few signs or words. There were significant differences between receptive and expressive language in many patients, with more severe delays in expressive language. Twenty-four children and young adults, aged 6 to 27 years, underwent the age appropriate Wechsler Intelligence Scale. Among these patients Full Scale 10 scores ranged from mild mental retardation to average with the mean Full Scale 10 in the borderline range; 12.5% of patients attained Full Scale 10 scores in the average range, 16.7% in the low average range, 41.7% in the borderline range, and 29.8% in the retarded range. Detailed analysis of the battery became important. As an example, 1 patient had a Verbal IQ of 111, which was in the above average range, but a Performance 10 of 65, which fell in the retarded range bringing his Full Scale 10 down to 87, in the low average range. This split between Verbal and Performance 10 was consistent with a nonverbal-learning disability. The profile of a non-verbal learning disability was subsequently demonstrated in 54% of patients, with a mean Verbal 10 of 80 ±13 and a mean Performance 10 of 70 ±11. For 16 of 24 patients, the Performance 10 was 2 to 46 points lower than the Verbal IQ. For 8 of the 24 patients, the Performance IQ was 1 to 11 points higher than the Verbal IQ. Only one patient displayed a Performance IQ that was significantly higher than the verbal IQ. Of note, three of the eight patients who did not demonstrate a significant Verbal IQ to Performance IQ discrepancy were older. Review of their school 10 test records revealed that all three displayed significant Verbal IQ to Performance IQ splits at a younger age with lower Performance IQ scores. In all three cases, the Verbal IQ scores had declined over time to meet the level of the Performance IQ scores. In summary, our data emphasizes the wide variability of the 22qll.2 deletion. It supports the need to screen patients with combinations of the aforementioned abnormalities. And it serves to highlight the importance of systematic evaluations of patients with the 22ql 1.2 deletion.