Terminal 22q deletion syndrome: A newly recognized cause of speech and language disability in the autism spectrum

被引:121
作者
Manning, MA
Cassidy, SB
Clericuzio, C
Cherry, AM
Schwartz, S
Hudgins, L
Enns, GM
Hoyme, HE
机构
[1] Stanford Univ, Sch Med, Dept Pediat, Div Med Genet, Stanford, CA 94305 USA
[2] Univ Calif Irvine, Sch Med, Dept Pediat, Div Human Genet, Irvine, CA 92717 USA
[3] Univ New Mexico, Sch Med, Dept Pediat, Div Clin Genet Dysmorphol, Albuquerque, NM 87131 USA
[4] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
[5] Case Western Reserve Univ, Sch Med, Ctr Human Genet, Cleveland, OH USA
关键词
22q deletion syndrome; autism; speech and language disability; fluorescence in situ hybridization;
D O I
10.1542/peds.114.2.451
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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.
引用
收藏
页码:451 / 457
页数:7
相关论文
共 36 条
[1]   FISH-mapping of a 100-kb terminal 22q13 deletion [J].
Anderlid, BM ;
Schoumans, J ;
Annerén, G ;
Tapia-Paez, I ;
Dumanski, J ;
Blennow, E ;
Nordenskjöld, M .
HUMAN GENETICS, 2002, 110 (05) :439-443
[2]   Subtelomeric rearrangements detected in patients with idiopathic mental retardation [J].
Anderlid, BM ;
Schoumans, J ;
Annerén, G ;
Sahlén, S ;
Kyllerman, M ;
Vujic, M ;
Hagberg, B ;
Blennow, E ;
Nordenskjöld, M .
AMERICAN JOURNAL OF MEDICAL GENETICS, 2002, 107 (04) :275-284
[3]  
BARCH MJ, 1997, CYTOGENETICS LAB MAN, P100
[4]   Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome [J].
Bonaglia, MC ;
Giorda, R ;
Borgatti, R ;
Felisari, G ;
Gagliardi, C ;
Selicorni, A ;
Zuffardi, O .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 69 (02) :261-268
[5]   A boy with a submicroscopic 22qter deletion, general overgrowth and features suggestive of FG syndrome [J].
de Vries, BBA ;
Bitner-Glindzicz, M ;
Knight, SJL ;
Tyson, J ;
MacDermot, KD ;
Flint, J ;
Malcolm, S ;
Winter, RM .
CLINICAL GENETICS, 2000, 58 (06) :483-487
[6]   Cryptic terminal rearrangement of chromosome 22q13.32 detected by FISH in two unrelated patients [J].
Doheny, KF ;
McDermid, HE ;
Harum, K ;
Thomas, GH ;
Raymond, GV .
JOURNAL OF MEDICAL GENETICS, 1997, 34 (08) :640-644
[7]  
EVRIES BBA, 2001, J MED GENET, P145
[8]   THE DETECTION OF SUBTELOMERIC CHROMOSOMAL REARRANGEMENTS IN IDIOPATHIC MENTAL-RETARDATION [J].
FLINT, J ;
WILKIE, AOM ;
BUCKLE, VJ ;
WINTER, RM ;
HOLLAND, AJ ;
MCDERMID, HE .
NATURE GENETICS, 1995, 9 (02) :132-140
[9]  
Goizet C, 2000, AM J MED GENET, V96, P839, DOI 10.1002/1096-8628(20001204)96:6<839::AID-AJMG29>3.3.CO
[10]  
2-I