Asperger Syndrome: Causes

Pathogenesis (development of the disease)

The cause of autism/Asperger syndrome often remains unclear. Studies currently focus on the oxytocin receptor gene (OXTR) as a risk factor.

Etiology (Causes)

Biographic causes

Genetic burden from parents, grandparents (52.4%).
- Genetic risk dependent on gene polymorphisms:
  - Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
    - Genes: SLC25A12
    - SNP: rs4307059 in an intergenic region [autism spectrum disorders (ASD)].
      - Allele constellation: CT (1.19-fold).
      - Allele constellation: TT (1.42-fold)
    - SNP: rs2056202 in the gene SLC25A12 [autism spectrum disorders (ASD)].
      - Allele constellation: CT (0.8-fold).
      - Allele constellation: TT (0.64-fold)
    - SNP: rs2292813 in the gene SLC25A12 [autism spectrum disorders (ASD)].
      - Allele constellation: CT (0.75-fold).
      - Allele constellation: TT (0.56-fold)
    - SNP: rs10513025 in an intergenic region [autism spectrum disorders (ASD)].
      - Allele constellation: CT (0.55-fold).
      - Allele constellation: CC (> 0.55-fold)
- Genetic diseases
  - Kanner syndrome – chromosome 7, 15 (unclear inheritance).
  - Asperger syndrome – chromosome 1, 3, 13 (unclear inheritance).
Age
- Maternal age at conception – increasing maternal age from 30 to 34 years of age to highest risk in mothers over 40 years of age.
- Age of father at conception > 40 years (5- to 6-fold higher risk for autistic traits than children born to fathers younger than 30 years of age
Smoking maternal grandmother – risk increase of.
- 67% that granddaughters will develop typically autistic traits (impaired social communication or repetitive behaviors)
- > 50% that granddaughters develop Asperger’s syndrome (autism spectrum disorder, ASD).
Migration status of parents (consensus-based statement).
Socioeconomic factors
- Unemployment (despite high levels of education)
- Low socioeconomic status

Disease-related causes

Psyche – nervous system (F00-F99; G00-G99)

Maternal alcohol abuse during pregnancy (excluded risk factor: this is associated with significant cognitive impairment, numerous organic malformations, and other behavioral abnormalities in the child; but not autism spectrum disorders)
Early childhood brain damage
Cerebellar hypoplasia – underdevelopment of the cerebellum.

Medications taken by the mother during pregnancy:

Antidepressants?
- Ingestion in second and/or third trimester (third trimester of pregnancy); 87% increase over children without exposure.
- A meta-analysis and two registry studies find no differences for autism in exposed and unexposed siblings after SSRI ingestion by pregnant women.
Misoprostol – active ingredient used for gastric ulcers.
Thalidomide – sedative / sleeping pill, which became known through the so-called thalidomide scandal.
Valproic acid / valproate – active substance used in epilepsy.

Environmental pollution – intoxications (poisonings).

Air pollutants
- Air pollution (diesel particulates, mercury, and lead, nickel, manganese and methylene chlorides).
- Exposure to particulate matter and nitrogen dioxide during pregnancy and the first year of life.
Prenatal exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs)Note: Polychlorinated biphenyls are among the endocrine disruptors (synonym: xenohormones) that, even in minute amounts, can damage health by altering the endocrine system.

Further

Rubella vaccination in pregnancy (consensus-based statement).