Hypospadias and increased risk for neurodevelopmental disorders.

Abstract

BACKGROUND:

Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients.

METHODS:

Registry study within a national cohort of all 9,262 males with hypospadias and their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with hypospadias and their brothers were matched with controls by year of birth and county. The following outcomes were evaluated (1) any psychiatric (2) psychotic, (3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum disorders (ASD), (10) intellectual disability, and (11) other behavioral/emotional disorders with onset in childhood.

RESULTS:

Patients with hypospadias were more likely to be diagnosed with intellectual disability (OR 3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls. Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1) and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5) in comparison to siblings of healthy individuals. A slightly higher, although not statistically significant, risk was found for intellectual disability (1.3; 1.0-1.9). No relation between other psychiatric diagnosis and hypospadias was found.

CONCLUSIONS:

This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD in their brothers, suggesting a common familial (genetic and/or environmental) liability.

• Authors: Agnieszka Butwicka, Paul Lichtenstein, Mikael Landén, Anna S Nordenvall, Anna Nordenström, Agneta Nordenskjöld, Louise Frisén
• Journal: Journal of child psychology and psychiatry, and allied disciplines (J Child Psychol Psychiatry) Vol. 56 Issue 2 Pg. 155-61 (Feb 2015) ISSN: 1469-7610 [Electronic] England
• PMID: 25048198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Topics

• Adolescent
• Adult
• Attention Deficit Disorder with Hyperactivity (epidemiology)
• Child
• Child Behavior Disorders (epidemiology)
• Child Development Disorders, Pervasive (epidemiology, genetics)
• Child, Preschool
• Comorbidity
• Humans
• Hypospadias (epidemiology, genetics)
• Intellectual Disability (epidemiology)
• Male
• Registries
• Risk
• Siblings
• Sweden (epidemiology)
• Young Adult