Further characterization of the new microdeletion syndrome of 16p11.2-p12.2

• Published in: American journal of medical genetics. Part A Vol. 149A; no. 6; pp. 1200 - 1204
• Main Authors: Battaglia, Agatino, Novelli, Antonio, Bernardini, Laura, Igliozzi, Roberta, Parrini, Barbara
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2009; Wiley-Liss
• Subjects: 16p11.2-p12.2 microdeletion syndrome; Abnormalities, Multiple; Adult and adolescent clinical studies; Biological and medical sciences; Child; chromosome aberration; Chromosome Aberrations; Chromosome Breakage; Chromosome Deletion; Chromosomes, Artificial, Bacterial; Chromosomes, Human, Pair 16; Developmental Disabilities; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; Female; Genetic Predisposition to Disease; Humans; Hyperkinesis; In Situ Hybridization, Fluorescence; Intellectual deficiency; Intellectual Disability; Language Disorders; language impairment; Medical genetics; Medical sciences; Motor Skills Disorders; multiple congenital anomalies/mental retardation syndrome; Muscle Hypotonia; Nervous system (semeiology, syndromes); Neurology; Nucleic Acid Hybridization - methods; Otitis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Syndrome; Chromosomal aberration; Microdeletion; Multiple; Chromosome; Congenital anomaly; Developmental disorder; Mental retardation; Syndrome; Language disorder; Characterization; Communication disorder; Malformation; 16p11.2―p12.2 microdeletion syndrome; multiple congenital anomalies/mental retardation syndrome; language impairment; Intellectual deficiency; chromosome aberration
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.32847

Using aCGH, we have identified a pericentromeric deletion, spanning about 8.2 Mb, within 16p11.2–p12.2 in a patient with developmental delay (DD) and dysmorphic features. This deletion arose de novo and is flanked by segmental duplications. The proposita was the only child of healthy nonconsanguineous parents, born after an uneventful pregnancy, at 40 weeks gestation, by normal delivery. She was referred to us at age ${\rm 3}{\raise0.5ex\hbox{$\scriptstyle {{\rm 10}}$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle {{\rm 12}}$}}$ years for evaluation of DD and absent speech. On examination, there were a flat face; low‐set, posteriorly rotated ears; high‐arched palate; hypotonic face; right single palmar crease; long, thin fingers; and a sacral dimple. Her height was at the 50th centile, weight at the 25th, and OFC at the 30th. Results of DNA FraX, HRB chromosomes, metabolic work‐up, audiologic evaluation, brain MRI, electroencephalogram, and heart/abdomen ultrasonography were normal. When last seen, aged 8 years, she had a moderate intellectual disability (ID) and poor speech. She was hyperactive with short attention span and difficulty in concentration, but, based on formal testing, did not have autism. Our patient shows common clinical features to the four individuals described by Ballif et al. [Ballif et al. (2007); Nat Genet 39:1071–1073], and further characterizes the new microdeletion syndrome of 16p11.2–p12.2. aCGH suggests that the deletions of all cases share the same distal breakpoint. Of note, the proximal breakpoint of our proposita overlaps the distal breakpoint of the autistic patients studied by Kumar et al. [Kumar et al. (2008); Hum Mol Genet 17:628–638] and Weiss et al. [Weiss et al. (2008); N Eng J Med 358:667–675], confirming that the 16p region carrying susceptibility to autism is more centromeric. Our observation further defines two different, contiguous 16p genomic regions, responsible for a distinct MCA/ID syndrome, and for autism, respectively. © 2009 Wiley‐Liss, Inc.