46,XY difference of sex development due to a cholesterol synthesis defect

Last reviewed

🖨 Print for my doctorAdvocacy Hub →
ORPHA:325511
Who is this for?
Show terms as
8Treatment centers

Where are you in your journey?

UniteRare data is sourced from FDA.gov, ClinicalTrials.gov, Orphanet, OMIM, and NORD.
Report missing data

Overview

46,XY difference of sex development (DSD) due to a cholesterol synthesis defect is a rare condition in which a person who has male chromosomes (46,XY) does not develop typical male physical features because of a problem in how the body makes cholesterol. Cholesterol is a building block the body needs to produce hormones, including testosterone and other sex hormones that guide male development before birth. When there is a defect in the cholesterol production pathway, the body cannot make enough of these hormones, which can lead to differences in how the genitals and reproductive organs form. Affected individuals may be born with genitalia that appear female, ambiguous, or incompletely male, even though their chromosomes are typically male. This condition falls under a group of disorders known as differences of sex development (DSD). The underlying cholesterol synthesis defects can also affect other body systems, potentially causing growth problems, intellectual disability, and various birth defects depending on the specific enzyme that is impaired. Smith-Lemli-Opitz syndrome (SLOS) is one of the best-known examples of a cholesterol synthesis disorder that can cause 46,XY DSD. Treatment is supportive and depends on the specific diagnosis. It may include cholesterol supplementation, hormone therapy, surgical options for genital differences, and psychological support. A team of specialists is usually needed to provide comprehensive care throughout life.

Also known as:

Key symptoms:

Ambiguous or atypical genitalia at birthUndescended testesSmall penis or micropenisHypospadias (urethral opening in an unusual position)Growth delay or short statureFeeding difficulties in infancyIntellectual disability or learning difficultiesBehavioral challengesDistinctive facial featuresExtra fingers or toes (polydactyly)Fused toes (syndactyly of second and third toes)Heart defectsCleft palateKidney abnormalitiesSensitivity to sunlight

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for 46,XY difference of sex development due to a cholesterol synthesis defect.

View clinical trials →

No actively recruiting trials found for 46,XY difference of sex development due to a cholesterol synthesis defect at this time.

New trials open frequently. Follow this disease to get notified.

Search ClinicalTrials.gov ↗Join the 46,XY difference of sex development due to a cholesterol synthesis defect community →

No specialists are currently listed for 46,XY difference of sex development due to a cholesterol synthesis defect.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to 46,XY difference of sex development due to a cholesterol synthesis defect.

Search all travel grants →NORD Financial Assistance ↗

Community

Open 46,XY difference of sex development due to a cholesterol synthesis defectForum →

No community posts yet. Be the first to share your experience with 46,XY difference of sex development due to a cholesterol synthesis defect.

Start the conversation →

Latest news about 46,XY difference of sex development due to a cholesterol synthesis defect

No recent news articles for 46,XY difference of sex development due to a cholesterol synthesis defect.

Follow this condition to be notified when news becomes available.

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 specific cholesterol synthesis defect does my child have, and which gene is affected?,How severe is my child's condition, and what can we expect in terms of development?,Should my child take cholesterol supplements, and how do we monitor if they are working?,What specialists should be part of our care team?,How should we approach decisions about surgery or hormone therapy, and when?,Are there any clinical trials or new treatments being studied for this condition?,What psychological and social support resources are available for our family?

Common questions about 46,XY difference of sex development due to a cholesterol synthesis defect

What is 46,XY difference of sex development due to a cholesterol synthesis defect?

46,XY difference of sex development (DSD) due to a cholesterol synthesis defect is a rare condition in which a person who has male chromosomes (46,XY) does not develop typical male physical features because of a problem in how the body makes cholesterol. Cholesterol is a building block the body needs to produce hormones, including testosterone and other sex hormones that guide male development before birth. When there is a defect in the cholesterol production pathway, the body cannot make enough of these hormones, which can lead to differences in how the genitals and reproductive organs form.

How is 46,XY difference of sex development due to a cholesterol synthesis defect inherited?

46,XY difference of sex development due to a cholesterol synthesis defect follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does 46,XY difference of sex development due to a cholesterol synthesis defect typically begin?

Typical onset of 46,XY difference of sex development due to a cholesterol synthesis defect is neonatal. Age of onset can vary across affected individuals.