46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome

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ORPHA:168563OMIM:607080Q56.1
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Overview

46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome is an extremely rare genetic condition that combines two major problems: abnormal development of the reproductive organs and progressive nerve damage. The "46,XY" part means that a person has the typical male chromosome pattern, but their gonads (the organs that would normally become testes) do not develop properly. This is called gonadal dysgenesis. As a result, affected individuals may be born with ambiguous genitalia or external genitalia that appear female, despite having male chromosomes. The condition is sometimes referred to as 46,XY DSD (disorder of sex development) with peripheral neuropathy. In addition to the reproductive differences, people with this syndrome develop motor and sensory neuropathy, which means the nerves that control movement and feeling gradually stop working well. This can lead to muscle weakness, numbness, tingling, and difficulty walking, typically worsening over time. The combination of gonadal dysgenesis and neuropathy in the same person distinguishes this syndrome from other forms of differences in sex development. Treatment is mainly supportive and depends on the individual's specific symptoms. Hormone replacement therapy may be needed to support puberty and bone health. Physical therapy and assistive devices can help manage the neuropathy. Gonadal tissue that has not developed properly may need to be surgically removed because of an increased risk of tumor development. A team of specialists is usually needed to provide comprehensive care.

Key symptoms:

Ambiguous genitalia at birthUnderdeveloped or streak gonadsMuscle weakness in the legs and armsNumbness or tingling in the hands and feetDifficulty walking or unsteady gaitReduced reflexesMuscle wasting, especially in the lower legsAbsent or incomplete puberty without treatmentFoot deformities such as high arches or hammertoesLoss of sensation in the extremitiesFatigue during physical activity

Clinical phenotype terms (26)— hover any for plain English
Hypoplasia of the uterusHP:0000013Abnormal female external genitalia morphologyHP:0000055Gonadal dysgenesisHP:0000133Abnormal vagina morphologyHP:0000142PolyneuropathyHP:0001271Abnormal peripheral myelinationHP:0003130Abnormality of peripheral nerve conductionHP:0003134Distal sensory impairment of all modalitiesHP:0003409Sensory ataxic neuropathyHP:0003434Decreased serum estradiolHP:0008214Dysplastic testisHP:0008733Gonadal dysgenesis with female appearance, maleHP:0008723
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 ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome.

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No actively recruiting trials found for 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome at this time.

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No specialists are currently listed for 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome.

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 gonadal dysgenesis-motor and sensory neuropathy syndrome.

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Community

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.What is the current status of my child's gonadal tissue, and is gonadectomy recommended?,When should hormone replacement therapy be started, and what are the options?,How quickly is the neuropathy expected to progress, and what signs should I watch for?,What genetic testing has been done, and should additional testing be considered?,What physical therapy or rehabilitation services would be most helpful right now?,Are there any clinical trials or research studies we could participate in?,What psychological support resources are available for our family?

Common questions about 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome

What is 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome?

46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome is an extremely rare genetic condition that combines two major problems: abnormal development of the reproductive organs and progressive nerve damage. The "46,XY" part means that a person has the typical male chromosome pattern, but their gonads (the organs that would normally become testes) do not develop properly. This is called gonadal dysgenesis. As a result, affected individuals may be born with ambiguous genitalia or external genitalia that appear female, despite having male chromosomes. The condition is sometimes referred to

How is 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome inherited?

46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome typically begin?

Typical onset of 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome is neonatal. Age of onset can vary across affected individuals.