DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY
LETTER TO THE EDITOR
Chromosomal microarray among children with intellectual disability: a useful diagnostic tool for the clinical geneticist Stephanie Capobianco1, Sebastiano AG Lava1,2, Mario G 1,2
3
3
Bianchetti , Danielle Martinet , Marco Belfiore , Gian Paolo Ramelli1, Alessandra Ferrarini1,3 1 Integrated Department of Pediatrics, Ente Ospedaliero Cantonale Ticinese, Bellinzona; 2 University of Bern, Bern; 3 Medical Genetic Service Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Correspondence to: [email protected] doi: 10.1111/dmcn.12341
SIR–Developmental delay and intellectual disability occur in 2% to 3% of the population and present either as isolated or in the context of a recognized syndromic condition. Chromosomal microarray is now widely recommended as a firsttier investigation in individuals with unexplained developmental delay.1 We would like to describe our experience with this technique.2 Between April 2008 and March 2012, we collected data on 123 participants less than 22 years of age with developmental delay or intellectual disability. All patients were evaluated both by a neurologist (GR) and a clinical geneticist (AF). Participants with a history of drug exposure during pregnancy and neonatal hypoxic-ischemic brain injury had been excluded. In these patients, neurological examination revealed developmental delay or intellectual disability such as language or motor impairment, muscular hypotonia, or autistic traits. Out of the 123 considered cases, 39 (32%) presented with clinical features consistent with a well-known genetic condition, whose diagnosis was confirmed by means of specific tests such as standard karyotype, fluorescence in situ hybridization, or molecular biology studies. Chromosomal
microarray analysis was undertaken only in the remaining 84 (68%) patients, who did not present any pathognomonic phenotype. Previously reported microdeletion (n=9), microduplication (n=11), both microdeletion or microduplication (n=3) syndromes, or a mosaic for chromosome 9p (n=1) were found in 24 individuals (nine females, 15 males; aged between 2mo and 22 y, median 6 y 6 mo) out of 84 cases (28%). Chromosomal microarray studies performed among patients’ parents demonstrated that the detected syndromes were de novo in seven (29%) and familial in nine (38%) out of 24 cases. No chromosomal microarray studies were performed in the parents of the remaining eight cases (33%). According to the literature, chromosomal microarray detects abnormalities in approximately 15% of patients with developmental delay or intellectual disability.3–5 The improved diagnostic yield (about 30%) noted in our experience is likely to be related to the fact that we undertook array comparative genomic hybridization studies exclusively after an in-depth clinical evaluation by a skilled clinical geneticist, who was able to recognize a well-known genetic condition in many cases. Thus, chromosomal microarray analysis was performed in carefully selected cases. This is of paramount relevance, considering that chromosomal microarray is a sophisticated, demanding, and expensive laboratory technique. A CK N O W L E D G E M E N T S This study was supported by the Advisory Board of the Scientific Research of Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
REFERENCES 1. Kurian MA. The clinical utility of chromosomal micro-
3. Trakadis Y, Shevell M. Microarray as a first genetic test
array in childhood neurological disorders. Dev Med Child
in global developmental delay: a cost-effectiveness analy-
Neurol 2012; 54: 582–3.
sis. Dev Med Child Neurol 2011; 53: 994–9.
2. Ferrarini A, Jacquemont S, Popovic MB, Bonafe L, Mar-
4. Dale RC, Grattan-Smith P, Nicholson M, Peters GB.
tinet D. [A DNA chip: why and for whom]. Rev Med
Microdeletions detected using chromosome microarray in
Suisse 2010; 237: 390–6 (in French).
children with suspected genetic movement disorders: a
290
single-centre study. Dev Med Child Neurol 2012; 54: 618– 23. 5. Beaudet AL. The utility of chromosomal microarray analysis in developmental and behavioral pediatrics. Child Dev 2013; 84: 121–32.
© 2013 Mac Keith Press
LETTER TO THE EDITOR
Chromosomal microarray among children with intellectual disability: a useful diagnostic tool for the clinical geneticist Stephanie Capobianco1, Sebastiano AG Lava1,2, Mario G 1,2
3
3
Bianchetti , Danielle Martinet , Marco Belfiore , Gian Paolo Ramelli1, Alessandra Ferrarini1,3 1 Integrated Department of Pediatrics, Ente Ospedaliero Cantonale Ticinese, Bellinzona; 2 University of Bern, Bern; 3 Medical Genetic Service Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Correspondence to: [email protected] doi: 10.1111/dmcn.12341
SIR–Developmental delay and intellectual disability occur in 2% to 3% of the population and present either as isolated or in the context of a recognized syndromic condition. Chromosomal microarray is now widely recommended as a firsttier investigation in individuals with unexplained developmental delay.1 We would like to describe our experience with this technique.2 Between April 2008 and March 2012, we collected data on 123 participants less than 22 years of age with developmental delay or intellectual disability. All patients were evaluated both by a neurologist (GR) and a clinical geneticist (AF). Participants with a history of drug exposure during pregnancy and neonatal hypoxic-ischemic brain injury had been excluded. In these patients, neurological examination revealed developmental delay or intellectual disability such as language or motor impairment, muscular hypotonia, or autistic traits. Out of the 123 considered cases, 39 (32%) presented with clinical features consistent with a well-known genetic condition, whose diagnosis was confirmed by means of specific tests such as standard karyotype, fluorescence in situ hybridization, or molecular biology studies. Chromosomal
microarray analysis was undertaken only in the remaining 84 (68%) patients, who did not present any pathognomonic phenotype. Previously reported microdeletion (n=9), microduplication (n=11), both microdeletion or microduplication (n=3) syndromes, or a mosaic for chromosome 9p (n=1) were found in 24 individuals (nine females, 15 males; aged between 2mo and 22 y, median 6 y 6 mo) out of 84 cases (28%). Chromosomal microarray studies performed among patients’ parents demonstrated that the detected syndromes were de novo in seven (29%) and familial in nine (38%) out of 24 cases. No chromosomal microarray studies were performed in the parents of the remaining eight cases (33%). According to the literature, chromosomal microarray detects abnormalities in approximately 15% of patients with developmental delay or intellectual disability.3–5 The improved diagnostic yield (about 30%) noted in our experience is likely to be related to the fact that we undertook array comparative genomic hybridization studies exclusively after an in-depth clinical evaluation by a skilled clinical geneticist, who was able to recognize a well-known genetic condition in many cases. Thus, chromosomal microarray analysis was performed in carefully selected cases. This is of paramount relevance, considering that chromosomal microarray is a sophisticated, demanding, and expensive laboratory technique. A CK N O W L E D G E M E N T S This study was supported by the Advisory Board of the Scientific Research of Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
REFERENCES 1. Kurian MA. The clinical utility of chromosomal micro-
3. Trakadis Y, Shevell M. Microarray as a first genetic test
array in childhood neurological disorders. Dev Med Child
in global developmental delay: a cost-effectiveness analy-
Neurol 2012; 54: 582–3.
sis. Dev Med Child Neurol 2011; 53: 994–9.
2. Ferrarini A, Jacquemont S, Popovic MB, Bonafe L, Mar-
4. Dale RC, Grattan-Smith P, Nicholson M, Peters GB.
tinet D. [A DNA chip: why and for whom]. Rev Med
Microdeletions detected using chromosome microarray in
Suisse 2010; 237: 390–6 (in French).
children with suspected genetic movement disorders: a
290
single-centre study. Dev Med Child Neurol 2012; 54: 618– 23. 5. Beaudet AL. The utility of chromosomal microarray analysis in developmental and behavioral pediatrics. Child Dev 2013; 84: 121–32.
© 2013 Mac Keith Press
