The diagnostic utility of a genetics evaluation in children with pervasive developmental disorders

Genet Med. 2006 Jan;8(1):50-4. doi: 10.1097/01.gim.0000195304.45116.96.

Abstract

Purpose: A genetics evaluation of children with pervasive developmental disorders (PDDs) identifies a diagnosis in 6% to 15% of cases. However, previous studies have not measured the incidence of genetic disorders among children with autistic-like features who do not necessarily meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria for PDD.

Methods: We identified 101 patients at our institution referred for PDD, autism, Asperger syndrome, or autistic features. Seventy-eight were males and 23 were females, giving a male-to-female ratio of 3.4:1. No diagnosis was identified on examination alone, although Rett syndrome was suspected in six females. Seventeen patients did not undergo any type of testing because of noncompliance.

Results: Of the remaining 84 patients analyzed, seven (8.3%) were found to have abnormalities on testing. Three chromosomal anomalies were found: one with 5p duplication, one with low-level mosaicism for trisomy 21, and one with an unbalanced 10;22 translocation. Three females were diagnosed with Rett syndrome after MECP2 analysis identified a disease-causing mutation. The remaining patient was found to have an elevated urine orotic acid, with a normal ammonia level, of unknown significance.

Conclusion: On the basis of our series, the yield of a genetics evaluation in patients with features of PDD who do not necessarily meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria is 8.3%. Approximately half of these were the result of a chromosomal abnormality. Three cases of Rett syndrome were identified for which autistic behaviors are a well-described feature. These findings suggest that a high-resolution karyotype provides the greatest diagnostic yield for patients with autistic-like features. MECP2 analysis should be considered for females who present with autistic behaviors.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child Development Disorders, Pervasive / diagnosis*
  • Child Development Disorders, Pervasive / genetics*
  • Child, Preschool
  • Chromosome Aberrations*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Karyotyping
  • Male
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Sex Factors

Substances

  • Methyl-CpG-Binding Protein 2