Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum.
OBJECTIVE
Cryptic subtelomeric chromosome rearrangements account for 6% to 10% of idiopathic mental retardation. As cytogenetic and molecular techniques have become more sophisticated, the number of genetic syndromes attributed to these microdeletions has increased. To date, 64 patients have been described in the literature with a more recently recognized microdeletion syndrome, del 22q13.3. The purpose of this study is to present 11 new cases of this recently described syndrome to delineate further the phenotype and to alert the clinician to another genetic condition that should be considered in the differential diagnosis of early hypotonia, delayed speech acquisition, and autistic behavior.


METHODS
Eleven patients were evaluated in 3 academic institutions. Clinical features and results of cytogenetic testing were recorded and tabulated. Reasons for referral for genetic evaluation included developmental delay, severe expressive speech and language delay, and dysmorphic features.


RESULTS
Age of presentation ranged from 5 months to 46 years. There were 10 female patients and 1 male patient. All of the patients exhibited delayed motor development, some degree of hypotonia, and severe expressive speech and language delay. Dysmorphic facial features included epicanthal folds, large cupped ears, underdeveloped philtrum, loss of cupid's bow, and full supraorbital ridges. Six patients exhibited autistic-like behaviors. Microscopically visible chromosome deletions were observed in 6 patients. In the remainder, the deletion was detected with the use of fluorescence in situ hybridization.


CONCLUSIONS
Hypotonia and developmental delay are nonspecific findings observed in many malformation and genetic syndromes. However, in association with severe speech and language delay and autistic-like behavior, this phenotype may be a significant indication to consider the 22q13 deletion syndrome as a potential cause.
Manning
Melanie A
MA
Department of Pediatrics, Division of Medical Genetics, H-315, Stanford University School of Medicine, Stanford, California 94305-5208, USA. mmanning@stanford.edu
Cassidy
Suzanne B
SB
Clericuzio
Carol
C
Cherry
Athena M
AM
Schwartz
Stuart
S
Hudgins
Louanne
L
Enns
Gregory M
GM
Hoyme
H Eugene
HE
D000015:Abnormalities, Multiple / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D020732:Cytogenetic Analysis; D002658:Developmental Disabilities / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007806:Language Disorders / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D013064:Speech Disorders / Q000235:genetics*