Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood.
OBJECTIVE
The 22q13.3 deletion syndrome (Online Mendelian Inheritance in Man No. 606232) is a neurodevelopmental disorder that includes hypotonia, severely impaired development of speech and language, autistic-like behavior, and minor dysmorphic features. Although the number of reported cases is increasing, the 22q13.3 deletion remains underdiagnosed because of failure in recognizing the clinical phenotype and detecting the 22qter deletion by routine chromosome analyses. Our goal is to contribute to the description of the neurobehavioral phenotype and brain abnormalities of this microdeletional syndrome.


METHODS
We assessed neuromotor, sensory, language, communication, and social development and performed cerebral MRI and study of regional cerebral blood flow measured by positron emission tomography in 8 children carrying the 22q13.3 deletion.


RESULTS
Despite variability in expression and severity, the children shared a common developmental profile characterized by hypotonia, sleep disorders, and poor response to their environment in early infancy; expressive language deficit contrasting with emergence of social reciprocity from ages approximately 3 to 5 years; sensory processing dysfunction; and neuromotor disorders. Brain MRI findings were normal or showed a thin or morphologically atypical corpus callosum. Positron emission tomography study detected a localized dysfunction of the left temporal polar lobe and amygdala hypoperfusion.


CONCLUSIONS
The developmental course of the 22q13.3 deletion syndrome belongs to pervasive developmental disorders but is distinct from autism. An improved description of the natural history of this syndrome should help in recognizing this largely underdiagnosed condition.
Philippe
Anne
A
National Institute of Health and Medical Research and Department of Genetics, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. anne.philippe@necker.fr
Boddaert
Nathalie
N
Vaivre-Douret
Laurence
L
Robel
Laurence
L
Danon-Boileau
Laurent
L
Malan
Valérie
V
de Blois
Marie-Christine
MC
Heron
Delphine
D
Colleaux
Laurence
L
Golse
Bernard
B
Zilbovicius
Monica
M
Munnich
Arnold
A
D001927:Brain Diseases / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011379:Prognosis; D011584:Psychology; D011596:Psychomotor Disorders / Q000175:diagnosis / Q000235:genetics; D013064:Speech Disorders / Q000175:diagnosis / Q000235:genetics