Overview
Syndrome with 46,XX difference of sex development (DSD) refers to a group of rare conditions where a person has female chromosomes (46,XX) but their body develops features that do not match typical female anatomy. This can include ambiguous genitalia at birth, where the external sex organs may not clearly appear male or female, or in some cases, the body may develop more male-like features despite having female chromosomes. These conditions happen because of unusual hormone exposure or genetic changes that affect how the body develops sexually before birth. The term '46,XX DSD' replaces older terminology such as '46,XX disorders of sex development' or 'female pseudohermaphroditism.' There are several different syndromes that fall under this category, each with its own specific cause. Some are caused by excess androgen (male hormone) exposure during fetal development, while others involve genetic mutations that affect the development of the gonads (ovaries or testes) or the pathways that determine sex. Treatment depends on the specific underlying syndrome and may include hormone therapy, surgical options, and psychological support. A multidisciplinary team approach is essential, involving endocrinologists, surgeons, geneticists, and mental health professionals. Early diagnosis and supportive care can greatly improve quality of life. Gender identity, fertility concerns, and long-term hormonal health are important aspects of ongoing management.
Key symptoms:
Ambiguous genitalia at birthEnlarged clitorisPartially fused labiaAtypical urethral openingAbsence of typical female internal reproductive organs in some casesDelayed or absent pubertyLack of menstrual periodsInfertility or reduced fertilityDevelopment of male-pattern body hairDeepening of the voice during pubertyShort stature or unusual growth patternsSalt-wasting crisis in some forms (related to adrenal problems)Gonadal abnormalities such as streak gonads or ovotestes
Variable
Can be inherited in different ways depending on the underlying gene
Neonatal
Begins at or shortly after birth (first 4 weeks)
FDA & Trial Timeline
3 eventsEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Boston Children's Hospital — NA
Fondation Ophtalmologique Adolphe de Rothschild
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
No FDA-approved treatments are currently listed for Syndrome with 46,XX difference of sex development.
3 clinical trialsare actively recruiting — trials can provide access to cutting-edge therapies.
View clinical trials →Specialists
View all specialists →No specialists are currently listed for Syndrome with 46,XX difference of sex development.
Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
No travel grants are currently matched to Syndrome with 46,XX difference of sex development.
Community
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Caregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
Rare disease caregiving can be isolating. Connect with counseling and peer support.
Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Questions for your doctor
Bring these to your next appointment
- Q1.What is the specific cause of my child's condition, and which genes are involved?,Will my child need hormone replacement therapy, and when should it start?,What are the options regarding surgery, and what are the risks and benefits of waiting?,How will this condition affect my child's fertility in the future?,Should we be concerned about adrenal insufficiency, and do we need an emergency plan?,What psychological support services are available for our family?,Are there other family members who should be tested for this condition?
Common questions about Syndrome with 46,XX difference of sex development
What is Syndrome with 46,XX difference of sex development?
Syndrome with 46,XX difference of sex development (DSD) refers to a group of rare conditions where a person has female chromosomes (46,XX) but their body develops features that do not match typical female anatomy. This can include ambiguous genitalia at birth, where the external sex organs may not clearly appear male or female, or in some cases, the body may develop more male-like features despite having female chromosomes. These conditions happen because of unusual hormone exposure or genetic changes that affect how the body develops sexually before birth. The term '46,XX DSD' replaces older
At what age does Syndrome with 46,XX difference of sex development typically begin?
Typical onset of Syndrome with 46,XX difference of sex development is neonatal. Age of onset can vary across affected individuals.
Are there clinical trials for Syndrome with 46,XX difference of sex development?
Yes — 3 recruiting clinical trials are currently listed for Syndrome with 46,XX difference of sex development on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.