Clinical, cytogenetic and molecular study of children with autistic behavior

Abstract EN

Background : Autism is a pervasive developmental disorder of multifactorial origin with an evidence for strong genetic influences most likely involving more than one susceptibility gene together with an influence of environmental elements.

Aim : The study aimed to analyze some genetic aspects in a sample of individuals presenting with autistic features using a protocol of clinical and laboratory assessment.

Subjects and Methods : The study included 60 cases with a preliminary diagnosis of autism.

A comprehensive protocol comprising clinical interview, neurological and genetic examination was applied.

Etiological diagnosis comprised cytogenetic analysis, molecular testing of the fragile X syndrome and metabolic screening, when appropriate.

Finally, an association study investigating the possible involvement of serotonin transporter (5-HTT) gene variants in the etiology of autism was performed.

We examined two polymorphic loci in 5-HTT (on 17q) : HTTLPR and VNTR in intron 2.

Results : The study included 46 males and 14 females.

An etiological diagnosis was established in twenty one patients (35 %).

Ten cases were given a clinical diagnosis (5 Rett syndrome, 3 Angelman syndrome, 1 Sotos syndrome and 1 FG syndrome).

Metabolic investigations diagnosed three cases of PKU.

Molecular testing detected six cases of fragile X syndrome.

Chromosomal abnormalities were found in two cases.

The molecular study found evidence for association between autism and the long allele of HTTLPR, but no significant association with alleles at VNTR in intron 2 of 5-HTT.

Recommendations : The observation that an etiology for autism can be found in over a third of cases reinforces the notion that a referral to a geneticist is worthwhile, given the potential consequence of an etiologic diagnosis for recurrence risk estimation, more accurate prognostication, and possible therapeutic interventions.