Departments of Pediatrics, *Midland Regional , Hospital, Mullingar; and ^#Royal College of Surgeons, Dublin; Ireland.
Email: [email protected] 
   

We report on a boy who was brought to our Pediatric Early Intervention Clinic for evaluation of speech and language delay at 3 years of age. He was born by normal vaginal delivery at full term with birth weight, length and head circumference, 3.4 kgs (25th centile), 48 cm (9th centile) and 35 cm (25th centile), respectively. Physical and systemic examinations were normal with no dysmorphic features. Evaluation revealed delay in communication, fine motor and personal social skills. Hearing tests on two previous occasions were normal. He had tendency to repeat words (echolalia) and showed some stereotypic interests in his behaviour. Repeat psychological assessment after six months revealed deteriorating personal social skill with further decline in social interaction. A diagnosis of autistic spectrum disorder (DSM-IV–TR) was made. There was history of poor scholastic achievement in father in his young age but he did not have problems in communication or social interaction. Mother and grandparents had no such history.

Metabolic investigations were normal and cytogenetic study revealed normal male karyotype. Targeted array-based comparative genomic hybridization revealed a microdeletion of 540kbp from chromosome 7q33 (136,018,399-136,558,387) × 2 region. This deletion was merely encroaching the gene CHRM 2 which has a role in central nervous system functioning, although its exact role in autism has not been elucidated so far. Parental analysis revealed a loss of 42 kbp from the same 7q33 (136,258,387-136,300,365) × 2 region in father’s side. Maternal chromosomal analysis was normal.

The distal region of chromosome 7q is home to many important genes, the deletion/ duplication of which has been reported with varying phenotypes. Matsson, et al. [1] reported association of DGKI (diacylglycerol kinase iota) gene at chromosome 7q33 with developmental dyslexia in Finnish and German cohorts. Contactin Associated Protein-like 2　(CNTNAP2), a member of the Neurexin family gene located at 7q34 has been linked strongly with autism [2,3]. There are several other suspicious loci on different chromosomes which are supposed to be linked with autism. Speech and language region which has been most sought to be associated with autism lies at 7q31-33 with FOXP2 and WNT2 genes in region 7q31 being more specific to speech delay and autism, respectively [4,5].

Genetic anticipation is a phenomenon in which symptoms of a disease manifests earlier after passing on to next generations. Small deletion at 7q33 region in father with larger deletion at the same region in son alongwith early presentation of typical ASD features explains the possibility of anticipation in the inheritance of genes related with ASD at 7q33 region. Further clinical validation is important as it may have practical significance on genetic counselling and timing of surveillance initiation. Further research is needed to explore the underlying mechanism of anticipation related with chromosome 7q33 and autism.

1. Matsson H,　Tammimies K,　Zucchelli M,　　Anthoni H,　Onkamo P,　Nopola-Hemmi J, et al. SNP variations in the　7q33　region containing DGKI are associated with dyslexia in the Finnish and German populations. Behav Genet.　2011;41:134-40.

2. Alarcón M,　Abrahams BS,　Stone JL,　　Duvall JA,　Perederiy JV,　Bomar JM, et al. Linkage,　association, and　gene-expression　analyses　identify　CNTNAP2　as an　autism-susceptibility　gene. Am J Hum Genet.　 2008;82:150-9.

3. Rossi E,　Verri AP,　Patricelli MG,　　Destefani V,　Ricca I,　Vetro A, et al. A 12Mb deletion at 7q33-q35 associated with autism spectrum disorders and primary amenorrhea. Eur J Med Genet.　 2008;51:631-8.

4. Muhle R,　Trentacoste SV,　Rapin I. The genetics of autism. Pediatrics.　 2004;113:e472-86.