Overview
46,XX difference of sex development-skeletal anomalies syndrome (also known as Nivelon-Nivelon-Mabille syndrome) is an extremely rare genetic condition that affects both sexual development and bone formation. In this syndrome, a person has female chromosomes (46,XX) but their body develops with ambiguous or atypical genitalia, meaning the external sex organs may not clearly appear male or female. This is combined with significant skeletal abnormalities, which can include problems with bone growth, abnormal shape of the spine or limbs, and other structural differences in the skeleton. Key features of this condition include ambiguous genitalia at birth, short stature, skeletal malformations (such as abnormalities of the vertebrae, limbs, or ribs), and sometimes intellectual disability or developmental delays. Some affected individuals may also have facial differences or other organ involvement. Because this syndrome is so rare, there is no specific cure. Treatment focuses on managing individual symptoms. This may include hormone therapy to support appropriate sexual development, orthopedic care for bone problems, surgical correction of genital or skeletal abnormalities when needed, and developmental support services. A team of specialists working together is essential for the best possible care. Early diagnosis and intervention can help improve quality of life.
Key symptoms:
Ambiguous genitalia at birthShort statureAbnormal bone developmentSpine abnormalitiesLimb malformationsIntellectual disabilityDevelopmental delaysUnusual facial featuresGrowth restriction before birthAbnormal rib formation
Clinical phenotype terms (12)— hover any for plain English
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Neonatal
Begins at or shortly after birth (first 4 weeks)
Treatments
No FDA-approved treatments are currently listed for 46,XX difference of sex development-skeletal anomalies syndrome.
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Specialists
View all specialists →No specialists are currently listed for 46,XX difference of sex development-skeletal anomalies syndrome.
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 46,XX difference of sex development-skeletal anomalies syndrome.
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Caregiver Resources
NORD Caregiver Resources
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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 skeletal and genital findings does my child have, and how severe are they?,Will my child need hormone therapy, and if so, when should it start?,What surgical options are available, and what are the risks and benefits of each?,Should we pursue genetic testing such as whole exome sequencing to look for a cause?,What developmental support services should we set up for my child?,How will this condition affect my child's growth, puberty, and fertility?,Are there other families or support groups we can connect with?
Common questions about 46,XX difference of sex development-skeletal anomalies syndrome
What is 46,XX difference of sex development-skeletal anomalies syndrome?
46,XX difference of sex development-skeletal anomalies syndrome (also known as Nivelon-Nivelon-Mabille syndrome) is an extremely rare genetic condition that affects both sexual development and bone formation. In this syndrome, a person has female chromosomes (46,XX) but their body develops with ambiguous or atypical genitalia, meaning the external sex organs may not clearly appear male or female. This is combined with significant skeletal abnormalities, which can include problems with bone growth, abnormal shape of the spine or limbs, and other structural differences in the skeleton. Key feat
How is 46,XX difference of sex development-skeletal anomalies syndrome inherited?
46,XX difference of sex development-skeletal anomalies syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does 46,XX difference of sex development-skeletal anomalies syndrome typically begin?
Typical onset of 46,XX difference of sex development-skeletal anomalies syndrome is neonatal. Age of onset can vary across affected individuals.