ADVANCING PATERNAL AGE IS CONSISTENTLY ASSOCIATED WITH INCREASED RISK OF AUTISM AND ASDs

Alexander Kolevzon, MD; Raz Gross, MD, MPH; Abraham Reichenberg, PhD

Vol. 161 No. 4, April 2007



The results of this review show that 3 of the 4 population-based studies28-29,32 to examine paternal age reported a significant association with risk of autism and ASDs. The fourth study31 also found that paternal age was older in fathers of case patients with autism compared with fathers of controls, although this relationship was statistically weaker in the adjusted analysis. Thus, advancing paternal age is consistently associated with increased risk of autism and ASDs.
Advanced paternal age has been associated with several congenital disorders, including Apert syndrome,40 craniosynostosis,41 situs inversus,42 syndactyly,43 cleft lip and/or palate,44-45 hydrocephalus,44 neural tube defects,46 and Down syndrome.47 In addition, advanced paternal age has been associated with schizophrenia15 and decreased intellectual capacities in the offspring.48 The most widely proposed mechanism underlying these congenital anomalies is known as the "copy error" hypothesis, first proposed by Penrose.49 After puberty, spermatocytes divide every 16 days, and by the age of 35 years, approximately 540 cell divisions have occurred. As a result, de novo genetic mutations that result from replication errors and defective DNA repair mechanisms are believed to propagate in successive clones of spermatocytes. These mutations accumulate with advancing paternal age and thus help explain how this disorder, which has a large genetic component, can be maintained in the population despite reduced reproduction in affected individuals.



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Southwest Autism Research & Resource Center (SARRC)
PREVALENCE OF PSYCHIATRIC AND LEARNING DISORDERS IN MULTIPLEX, ONLY-CHILD, SINGLETON, AND CONTROL FAMILIES

S. E. Ober-Reynolds, R. D. Melmed, R. C. Bay, S. M. Stephens, J. J. Jones, S. E. Brautigam, J. E. Kirwan, T. A. Grebe
Enter abstract here-DON'T include authors or title
Background: While specific genes have been implicated in the etiology of autism, a history of psychiatric and learning disorders (psych/LD) in family members may increase a childs vulnerability to autism as well as these disorders.

Objectives: To compare the family history of psych/LD disorders in four groups: multiplex families, families whose only child has autism (only-child), families with one child with autism as well as unaffected children (singleton) and control families.

Methods: The prevalence of self-reported psych/LD was calculated using data from 1081 families who completed the SARRC Parent Questionnaire. Families were compared on reported history of the following: bipolar disorder, anxiety, depression, obsessive/compulsive disorder, ADHD, and learning disorders.

Results: Of the families, 52(4.8%) were multiplex, 131(12.1%) only-child, 584(54%) singleton, and 308(29.0%) controls. Prevalence of each psych/LD disorder differed across family type (chi-square exact tests, two-tailed), all p<0.001. The trend for prevalence was identical for all disorders analyzed; multiplex families reported the greatest prevalence (by family history) of each disorder followed by only-child families, singleton families, then control families.

Conclusion: Reported family history of psychiatric and learning disorders occurs most frequently in multiplex families and least in control families suggesting a genetic vulnerability which may predispose an individual to a spectrum of disorders, including autism.