Genetics of Differences of Sex Development and Hypospadias

Study Overview
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Brief Summary
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This study seeks to identify genetic causes of conditions that affect the gonads and genitals, and to study the impact on families of receiving genetic results.

Detailed Description
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This study seeks to understand the genetic causes of conditions that affect the development of the genitals, such as differences of sex development (DSD) and hypospadias, and the impact on families of receiving genetic results. The investigators are recruiting individuals with DSD and/or hypospadias without a clear genetic cause along with their family members for our research study. The investigators will collect samples for genetic studies. The investigators will review the clinical record for history, labs and physical exam information. The investigators will also build a tissue bank of blood, urine, and discarded tissues from surgeries. The investigators will return results of genetic testing to parents/guardians of children with DSD/hypospadias and have them complete questionnaires to assess the impact of receiving these results.

Official Title
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Utilizing Whole Exome Sequencing and Genomics to Improve Our Understanding of Differences of Sex Development (DSD) and Hypospadias

Conditions
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Disorders of Sex Development, Hypospadias

Intervention / Treatment
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* Genetic: Return of Genetic Results


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genital or gonadal abnormalities as evidenced by physical examination or imaging (including but not limited to hypospadias, microphallus, clitoromegaly, ambiguous genitalia), with no cause identified by standard clinical evaluation Exclusion Criteria: Inability to provide informed consent
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Longitudinal cohort
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genetic Testing<br>Subjects will provide a DNA sample, which will be screened for variants in genes related to DSD/hypospadias. Probands/parents who wish to receive results of genetic testing related to DSD/hypospadias will receive these results directly from the research study. Parents who receive results of genetic testing for probands 17 years old or younger will complete questionnaires at the time of enrollment, right after receiving genetic results, and 3 months after receiving genetic results. | Genetic: Return of Genetic Results<br>* The results of testing for genetic causes of DSD/hypospadias will be returned to parents of subjects who elect to receive these results.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decision Regret | Score on Decision Regret Scale | 3 months after return of genetic results | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parenting-Related Stress | Score on Parenting Stress Index | 3 months after return of genetic results compared to baseline | 
| Child Health-Related Stress | Score on Child Health Worry Scale | 3 months after return of genetic results compared to baseline | 
| Anxiety | Score on Generalized Anxiety Disorder-7 | 3 months after return of genetic results compared to baseline | 
| Depression | Score on Patient Health Questionnaire-9 | 3 months after return of genetic results compared to baseline | 
| Partner Relationship | Score on Kansas Marital Satisfaction Scale | 3 months after return of genetic results compared to baseline | 
| Partner Blame | Score on this novel measure | 3 months after return of genetic results compared to baseline | 
| Stigma | Score on Questionnaire, Stigma Related to Having a Child with a Urogenital Condition | baseline, 3 months after return of genetic results | 
| Quality of Life score | Score on Questionnaire, Quality of Life Related to Having a Child with a Urogenital Condition | baseline, 3 months after return of genetic results | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exome Sequencing