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Should children with ADHD and normal intelligence be routinely screened for underlying cytogenetic abnormalities?
  1. E Stephen,
  2. A D Kindley
  1. Royal Aberdeen Children’s Hospital, Aberdeen, UK; elma.stephen{at}

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You are assessing a 7 year old boy with attention and behaviour difficulties, and poor school performance. He has an average IQ and meets the diagnostic criteria for attention deficit hyperactivity disorder (ADHD). There is no evidence of developmental delay, dysmorphism, or other physical abnormalities and no relevant family history. Parents are keen on investigation for a “cause” for his problems. You are aware that some chromosomal and cytogenetic abnormalities may be associated with ADHD. You wonder if you should check karyotype and look for cytogenetic abnormalities with genetic implications for the family.

Structured clinical question

Should children with ADHD and normal intelligence [subject] be routinely screened* [intervention] for underlying cytogenetic abnormalities [outcome with genetic implications]?

Search strategy and outcome

OVID Medline and EMBASE search: “ADHD” AND (“cytogenetics” OR “human chromosomes”). A total of 61 articles were obtained combining these searches. After searching abstracts, 10 relevant articles were retrieved. (The remainder were mainly studies attempting to map ADHD to one/several gene loci using various genetic techniques, including linkage analyses. In the absence of routine and widespread availability of these tests, and their unproven clinical use, they were not considered.)

Secondary sources: Cochrane Library, Best Bets: no papers found.

Search date: September 2005.


Behaviour and cognitive problems including ADHD in children have been associated with several chromosomal and cytogenetic abnormalities. The most notable of these include velocardiofacial syndrome (VCFS),1 fragile X syndrome,2 sex chromosome aneuploidies (SCA),3,4 the X-linked condition Simpson–Golabi–Behmel syndrome, partial trisomy of chromosome 16, as well as certain balanced translocations. Some investigators have suggested that cytogenetic analyses should be considered in children with ADHD.5 However, most evidence to date suggests that these abnormalities are found with increased frequency in children with a learning disability (IQ <80) in addition to ADHD.

Using the search strategy above, there was only a single exploratory study6 identified that assessed the prevalence of genetic abnormalities in an unselected population of 100 children with ADHD and IQ >80 (see table 1). Giemsa banded karyotype testing for sex and other chromosomal abnormalities, and specific abnormalities for fragile X and VCFS, were performed on this group, with the hypothesis that there would be an increased rate of these abnormalities collectively than in the general population. There were no subjects found with either the fragile X mutation or chromosome 22q11.2 deletion for VCFS. Only one subject had a clear cytogenetic abnormality (a girl with trisomy 47, XXX), and this did not differ significantly from that expected in the general population (1/426). This child was clinically indistinguishable from the other subjects with regard to ADHD symptoms but had slightly lower reading and written language achievement scores.

Table 1

 Prevalence of cytogenetic abnormalities in an unselected population of children with ADHD

Although limited by a small sample size, this study showed that children with ADHD and average IQ do not display higher rates of cytogenetic abnormalities. However, definite evidence can only be obtained from larger well controlled studies as many of the conditions mentioned, especially SCA, can remain clinically unrecognised in subjects with normal intelligence. Testing for these abnormalities is expensive and at present, is not indicated in the absence of clinical indications such as developmental delay, relevant physical signs, positive family history, or learning disability.

There were numerous case reports and uncontrolled cohort studies looking at ADHD and specific populations of children with cytogenetic abnormalities7–,15 (see table 2).

Table 2

 Case reports and uncontrolled cohort studies linking ADHD with cytogenetic abnormalities in selected groups of children

Currently there is considerable research interest in genetic polymorphisms and particular behavioural phenotypes including ADHD. This is a rapidly expanding field and is likely to link particular genotypes with the ADHD phenotype. However, at present none of these research tools has been shown to be of particular use to the clinician.


  • There is limited evidence from an uncontrolled study that children with ADHD and normal intelligence do not display higher rates of underlying cytogenetic abnormalities (Grade D). Testing for these is therefore not indicated at present. Large well controlled studies would be required to provide more definite evidence

  • Cytogenetic abnormalities are more commonly found in the presence of learning disability, developmental delay, relevant physical signs or positive family history, and testing should be limited to these situations (Grade D)



  • * Karyotype, fragile X mutation analysis, FISH for 22q11.2 deletion, and high resolution chromosome banding for other cytogenetic abnormalities.

  • Bob Phillips