Prenatalna diagnostyka i leczenie matki sirolimuzem w zespole PMSE (wodniaku płodu, powiększeniu mózgu i padaczce)
Antenatal diagnosis and maternal sirolimus treatment of polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome
W skrócie
Zespół PMSE to bardzo rzadka choroba genetyczna, w której płód ma za dużo płynu owodniowego, powiększony mózg i ryzyko padaczki. Lekarze podali matce lek (sirolimuz) od 36. tygodnia ciąży, co zmniejszyło ilość płynu i wielkość głowy płodu, a dziecko urodziło się prawidłowo. Lek był bezpieczny dla matki i dziecka, choć po urodzeniu dziecko miało problemy z rozwojem typowe dla tej choroby.
Oryginalny abstract (angielski)
BACKGROUND: Polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome is a rare autosomal recessive mTORopathy caused by biallelic STE20-related kinase adaptor alpha () loss-of-function variants. Animal models demonstrate that in utero mechanistic target of rapamycin (mTOR) inhibition can prevent cortical dyslamination, suggesting a prenatal therapeutic window. METHODS: A gravida 3 para 2 patient presented at 32+2 weeks with medication-refractory preterm labor and severe polyhydramnios. Fetal magnetic resonance imaging (MRI) demonstrated macrocephaly and an enlarged cavum septum pellucidum (CSP). Amniocentesis with microarray revealed homozygosity across the locus; sequencing confirmed the founder exons 9-13 deletion. After counseling, maternal sirolimus therapy was initiated at 35+6 weeks using a 20 mg loading regimen followed by 6-8 mg/day maintenance dosing. Serial ultrasound monitored fetal biometry and CSP size. Delivery occurred at 39+1 weeks. Pediatric follow-up was extended nearly 5 years. RESULTS: Maternal sirolimus was well tolerated. Amniotic fluid index (AFI) declined from 36.1 to 26.2 cm, head circumference normalized from the 89th to 35th percentile, and CSP diameter decreased from 14.0 to 12.3 mm. A term vaginal delivery produced a 3554 g infant with normocephaly. Cord blood sirolimus level (3.9 mcg/L) approximated maternal level (3.4 mcg/L). Postnatally, sirolimus was continued from day of life 7. The first seizure occurred at 4.5 months, coincident with subtherapeutic trough levels; seizure control was achieved thereafter. At nearly 5 years, the child shows adequate growth but severe global developmental delay typical of PMSE.This case demonstrates the feasibility and pharmacokinetic effectiveness of maternal sirolimus during late gestation, with no identified maternal or fetal adverse consequences in this first case of third-trimester prenatal mTOR inhibition in confirmed PMSE.