How to evaluate a pregnancy with a history of two neonatal deaths due to Epidermolysis Bullosa Simplex (EBS)?

Evaluation of Pregnancy with History of Two Neonatal Deaths Due to Epidermolysis Bullosa Simplex

Genetic counseling and prenatal diagnosis should be offered immediately to any pregnant woman with a history of two neonatal deaths from Epidermolysis Bullosa Simplex (EBS), as this is essential for determining recurrence risk and management options. 1

Genetic Evaluation Algorithm

1. Initial Genetic Consultation

   • Obtain detailed family history focusing on consanguinity
   • Review medical records of previous affected neonates
   • Determine inheritance pattern (likely autosomal dominant or recessive)
   • Most EBS cases involve mutations in KRT5 and KRT14 genes 2

2. Molecular Diagnostic Testing

   • DNA analysis of parents to identify carrier status
   • Determine if previous cases were due to:
     • De novo mutations (lower recurrence risk)
     • Inherited mutations (higher recurrence risk)
     • Possible germline mosaicism 2

3. Prenatal Diagnostic Options

   • Chorionic villus sampling (10-12 weeks gestation)
   • Amniocentesis (15-18 weeks gestation)
   • Preimplantation genetic diagnosis if planning future pregnancies 1, 3

Management During Pregnancy

1. Multidisciplinary Team Approach

   • High-risk maternal-fetal medicine specialist
   • Dermatologist with EB expertise
   • Genetic counselor
   • Neonatologist 1

2. Prenatal Care Considerations

   • Regular ultrasound monitoring for fetal growth
   • Detailed anomaly scan to check for associated conditions (e.g., pyloric atresia)
   • Plan for delivery at a tertiary care center with EB expertise 1

3. Delivery Planning

   • Prepare specialized delivery kit with:
     • Soft blankets for handling newborn
     • Non-adherent dressings
     • Ligature for umbilical cord (instead of clamp) 1, 4
   • Avoid fetal scalp electrodes, vacuum extraction, or forceps 1

Postnatal Preparation

1. Immediate Neonatal Care

   • Secure umbilical cord with ligature rather than cord clamp 1, 4
   • Cover any birth trauma with non-adherent dressing 1
   • Apply emollient to suction catheter tips if needed 1
   • Avoid adhesive monitoring devices 1

2. Diagnostic Confirmation

   • Skin biopsy for antigen mapping and electron microscopy
   • Molecular genetic testing to confirm diagnosis 1, 5

Psychosocial Support

1. Emotional Support

   • Provide ongoing education and psychosocial support throughout pregnancy 1
   • Connect with DEBRA organization for community support 1
   • Offer psychological support, especially if transfer to specialized center is required 1

2. Decision Support

   • Discuss realistic expectations and prognosis based on genetic findings 1
   • Support ethical or moral dilemmas if severe forms of EB are suspected 1

Important Considerations and Pitfalls

• Diagnostic Accuracy: EBS is often confused with other forms of EB (junctional or dystrophic). Accurate genetic diagnosis is crucial for proper counseling about prognosis 6, 5

• Recurrence Risk Assessment: The risk varies significantly based on:

  • Autosomal dominant EBS: 50% risk if parent affected
  • Autosomal recessive EBS: 25% risk if both parents are carriers
  • De novo mutations: Very low recurrence risk in future pregnancies 2, 7

• Maternal Contamination: When performing prenatal diagnosis, ensure maternal contamination of fetal samples is avoided to prevent false results 3

• Subtype Determination: Different EBS subtypes have varying prognoses - from mild (localized EBS) to severe/lethal (Dowling-Meara EBS) 6, 5

The molecular diagnosis enables appropriate genetic counseling regarding inheritance pattern, recurrence risk, and options for prenatal diagnosis, while also establishing a reasonable clinical prognosis for the current pregnancy 5.