Genetics of Differences of Sex Development and Hypospadias

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Disorders of Sex Development; Hypospadias
• Intervention / Treatment: Genetic: Return of Genetic Results

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alayna Dutcher, BA; Phone Number: 6173550741; Email: alayna.dutcher@childrens.harvard.edu
• Study Contact Backup: Name: Sarah Schlegel, MD; Email: sarah.schlegel@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Genetic Testing; 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; The results of testing for genetic causes of DSD/hypospadias will be returned to parents of subjects who elect to receive these results.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Investigators: Principal Investigator: Yee-Ming Chan, MD, PhD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 27, 2017
• First Submitted That Met QC Criteria: March 30, 2017
• First Posted (Actual): April 5, 2017

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Exome Sequencing
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Urogenital Abnormalities; Congenital Abnormalities; Penile Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Hypospadias; Disorders of Sex Development
• Other Study ID Numbers: IRB-P00012912

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No