Is there cause for concern regarding fertility if a patient is a carrier of steroid-resistant nephrotic syndrome (SRNS)?

Carrier Status for Steroid-Resistant Nephrotic Syndrome and Fertility

Being a carrier for steroid-resistant nephrotic syndrome (SRNS) does not typically cause concern for fertility, as carrier status alone generally does not affect reproductive function or fertility outcomes.

Understanding Carrier Status for SRNS

Carrier status for SRNS means an individual has one copy of a gene mutation associated with SRNS, which is typically inherited in an autosomal recessive manner. Key points to understand:

• Carriers of recessive conditions like SRNS typically do not develop the disease themselves
• On average, individuals carry approximately 2 recessive variants across their genome 1
• Over 30 genes have been identified as causing monogenic forms of SRNS 2
• The identification of carrier status is extremely common in genetic testing, with >90% of infants having at least one carrier-status variant 1

Implications for Fertility

Direct Effects on Fertility

• No evidence suggests that being a carrier for SRNS directly affects fertility
• Unlike active SRNS or lupus nephritis, carrier status does not typically impact reproductive function

Reproductive Planning Considerations

• The primary consideration is the risk of having children with SRNS if both partners are carriers for mutations in the same SRNS-associated gene
• If both parents are carriers of mutations in the same gene, there is a 25% chance that their child will have SRNS

Benefits of Knowing Carrier Status

Knowing carrier status for SRNS provides several benefits:

• Allows for informed reproductive decision-making before pregnancy planning 1
• Provides time to learn about the condition and understand potential risks
• Enables cascade testing of the partner to determine if they are also a carrier
• May reduce psychosocial harm by allowing for preparation and planning 1

Management Recommendations

For individuals identified as carriers of SRNS:

1. Partner Testing: Consider genetic testing for the partner to determine if they also carry mutations in the same SRNS-associated gene

2. Genetic Counseling: Seek genetic counseling to understand:

   • The specific gene involved
   • The inheritance pattern
   • Reproductive options

3. Reproductive Options if both partners are carriers:

   • Preimplantation genetic diagnosis
   • Prenatal diagnosis
   • Donor gametes
   • Adoption

Important Considerations

• The risk of having a child with SRNS only exists if both parents carry mutations in the same gene
• The severity of SRNS varies widely depending on the specific genetic mutation
• Some forms of genetic SRNS may be amenable to treatment (e.g., those involving coenzyme Q10 biosynthesis genes) 3
• The risk of post-transplant disease recurrence is lower in hereditary SRNS than in non-genetic forms 4

Conclusion

While being a carrier for SRNS has implications for reproductive planning, it does not directly affect fertility. The primary consideration is the potential risk of having children with SRNS if both partners carry mutations in the same gene. Genetic counseling and partner testing are recommended to fully understand and manage these risks.