Specific Genetic Disorders and Autism: Clinical Contribution Towards their Identification

Abstract

Autism is a heterogeneous disorder that can reveal a specific genetic disease. This paper describes several genetic diseases consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, duplication of 15q11-q13, Down syndrome, San Filippo syndrome, MECP2 related disorders, phenylketonuria, Smith-Magenis syndrome, 22q13 deletion, adenylosuccinate lyase deficiency, Cohen syndrome, and Smith-Lemli-Opitz syndrome) and proposes a consensual and economic diagnostic strategy to help practitioners to identify them. A rigorous initial clinical screening is presented to avoid unnecessary laboratory and imaging studies. Regarding psychiatric nosography, the concept of "syndromal autism"--autism associated with other clinical signs should be promoted because it may help to distinguish patients who warrant a multidisciplinary approach and further investigation.

Genetic testing in autism: how much is enough?

“…The majority of the patients in our series were referred from our Autism Center rather than primary care providers and, hence, represented children with what has been called "isolated" or "nonsyndromic" ASD. 6 To avoid skewing of our results, we excluded two children with apparent "syndromic" ASDs from our analysis.…”

“…There are several single gene disorders, such as fragile X syndrome, Rett syndrome, untreated phenylketonuria, and tuberous sclerosis, in which autistic features are prominent and common. 6 ASDs are also associated with several chromosome abnormalities, the most common of which is a duplication of 15q11-q13 that includes the region involved in Prader-Willi and Angelman syndromes. 7 However, known genetic causes account for 10% or less of ASD cases.…”

Probing genetic overlap among complex human phenotypes

“…Our analysis of genetic overlap reveals numerous correlations among disorders, many of which are well established (e.g., see refs. [3][4][5][6][7][8], whereas other correlations appear previously undescribed.…”

Genetic causes of syndromic and non‐syndromic autism

“…13 FXS is diagnosed in almost 5 ⁄ 100 of individuals with autism. 14 Several studies have investigated the relationship between factors such as IQ and sensory difficulties and the presence of autism in individuals with FXS. Hatton et al 13 reported that the level of the fragile X protein FMRP (familial mental retardation protein) was correlated with the level of autistic behaviour as measured by the Childhood Autism Rating Scale.…”