What are the implications of a young adult with dentinogenesis imperfecta (DI) donating eggs, considering the genetic nature of her condition?

Dentinogenesis Imperfecta in Egg Donation: Genetic Counseling and Management

You must provide comprehensive genetic counseling to this prospective egg donor about the autosomal dominant inheritance pattern of dentinogenesis imperfecta and strongly recommend against proceeding with egg donation unless the recipient couple fully understands and accepts the 50% risk of transmitting this genetic condition to offspring. 1

Understanding Dentinogenesis Imperfecta

Dentinogenesis imperfecta (DI) is an autosomal dominant hereditary condition affecting dentin development in both primary and permanent dentitions, with an incidence of 1 in 6,000 to 1 in 8,000. 2 The condition manifests as:

• Opalescent, amber, or grayish-blue to brown discolored teeth 3, 2
• Structural defects including bulbous crowns, short roots, and pulpal obliteration 3, 2
• Rapid and extensive tooth wear due to weakened dentin and enamel shearing 3, 2
• Small pulp chambers visible radiographically 2

Critical Genetic Implications for Egg Donation

Inheritance Pattern and Risk

Each child conceived from this donor's eggs will have a 50% chance of inheriting dentinogenesis imperfecta, as this is an autosomal dominant condition. 1 This risk applies regardless of:

• The recipient's genetic background 1
• Previous pregnancy outcomes 1
• Number of embryos transferred 1

Association with Osteogenesis Imperfecta

You must determine whether this donor has isolated DI or DI associated with osteogenesis imperfecta (OI), as this fundamentally changes the counseling. 1

• DI Type I occurs with osteogenesis imperfecta and results from mutations in COL1A1 or COL1A2 genes encoding type I collagen 1, 2
• DI Types II and III are isolated dental conditions caused by mutations in the DSPP gene (dentin sialophosphoprotein) 2
• If OI is present, offspring face risks of bone fragility, fractures, blue sclerae, hearing loss, and variable short stature in addition to dental problems 1

Mandatory Steps Before Proceeding

1. Comprehensive Medical Genetics Evaluation

Refer this donor immediately to a medical geneticist for formal evaluation before any egg donation proceeds. 1 This evaluation must include:

• Detailed family pedigree construction to identify other affected family members 1
• Clinical examination for signs of OI including blue sclerae, joint hypermobility, hearing assessment, and skeletal examination 1
• Radiographic skeletal survey if any suspicion of OI exists 1
• Biochemical or molecular genetic testing to identify the specific causative mutation 1

2. Genetic Testing Requirements

Molecular genetic testing is essential before egg donation to:

• Confirm the diagnosis and identify the specific mutation (DSPP for isolated DI, or COL1A1/COL1A2 for DI with OI) 1, 2
• Enable preimplantation genetic testing (PGT) for recipient couples who wish to avoid affected embryos 1
• Provide accurate recurrence risk counseling to the recipient couple 1
• Allow for prenatal diagnosis options in future pregnancies if desired 1

3. Recipient Couple Counseling

The recipient couple must receive detailed genetic counseling about:

• The 50% transmission risk with each pregnancy 1
• The clinical manifestations of DI, including lifelong dental problems requiring extensive treatment beginning in infancy 4, 2, 5
• Treatment burden: multiple dental procedures often under general anesthesia starting at 18-20 months of age, ongoing restorative work into adulthood 5
• Psychosocial impact of visible tooth discoloration and structural defects 4, 2
• Potential association with OI if not definitively ruled out 1, 2, 6
• Availability of PGT to select unaffected embryos if the mutation is identified 1

Reproductive Options if Proceeding

Preimplantation Genetic Testing

If the causative mutation is identified, PGT should be strongly recommended to the recipient couple to avoid transferring affected embryos. 1 This requires:

• Trophectoderm biopsy of 5-8 cells from blastocyst-stage embryos 7
• Single embryo transfer (eSET) of unaffected embryos only 8, 9, 7
• Vitrification and frozen embryo transfer protocol 7

Embryo Transfer Protocol

Regardless of whether PGT is performed, single embryo transfer must be practiced for all donor egg cycles to minimize multiple pregnancy complications. 8, 9 The European Society of Human Reproduction and Embryology mandates eSET for all donated embryo transfers with no exceptions. 8, 9

Clinical Pitfalls to Avoid

Do not proceed with egg donation without:

• Formal genetics consultation and testing 1
• Documented informed consent from the recipient couple acknowledging the genetic risks 1
• Clear documentation that the donor understands the implications of transmitting this condition 1

Do not assume isolated DI without ruling out OI, as approximately 20% of OI families have associated DI, and the skeletal manifestations may be subtle or unrecognized. 1

Quality of Life Considerations

Children with DI face significant morbidity including:

• Extensive dental treatment requirements beginning in early childhood and continuing throughout life 4, 2, 5
• Multiple procedures under general anesthesia in early childhood 5
• Aesthetic concerns affecting psychosocial development 4, 2
• Functional limitations from tooth wear and loss 4, 3, 2
• If OI is present, risk of fractures, skeletal deformity, and potential mortality in severe forms 1

The decision to use this donor should only proceed after the recipient couple demonstrates full understanding of these implications and the availability of PGT to prevent transmission has been discussed. 1