Prenatal molecular diagnosis of tuberous sclerosis complex

• Published in: American journal of obstetrics and gynecology 2009-03, Vol.200 (3), p.321.e1-321.e6
• Main Authors: Milunsky, Aubrey, MBBCh, DSc, FRCP, FACMG, DCH, Ito, Masamichi, PhD, Maher, Thomas A., MS, Flynn, Maureen, MS, CGC, Milunsky, Jeff M., MD
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Family Health; Female; Genetic Counseling; Genetic Testing; Gynecology. Andrology. Obstetrics; Heart Neoplasms - diagnosis; Heart Neoplasms - epidemiology; Heart Neoplasms - genetics; Humans; Medical sciences; Neurology; Obstetrics and Gynecology; Polymorphism, Genetic; Pregnancy; prenatal diagnosis; Prenatal Diagnosis - methods; rhabdomyoma; Rhabdomyoma - diagnosis; Rhabdomyoma - epidemiology; Rhabdomyoma - genetics; Risk Factors; tuberous sclerosis; Tuberous Sclerosis - diagnosis; Tuberous Sclerosis - epidemiology; Tuberous Sclerosis - genetics; Tumor Suppressor Proteins - genetics; Tumors of the nervous system. Phacomatoses
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2008.11.004

Objective The objective of the study was to report experience with prenatal molecular diagnosis of tuberous sclerosis complex (TSC). Study Design Sequential deoxyribonucleic acid (DNA) studies were performed on amniotic fluid cells and chorionic villi from 50 pregnant women at risk for having a child with TSC. Mutations were determined by gene sequencing and deletion/duplication analysis of the 2 TSC genes. Results DNA analysis was successful in 48 of 50 tested fetuses. Mutations were precisely identified in a family member (24) (TSC1 [5]; TSC2 [19]) and/or fetus (11) (TSC1 [3]; TSC2 [8]). Novel mutations were found in 19 individual families, and a probable polymorphism was noted in 4. Second-trimester ultrasound detected 18 fetuses with cardiac rhabdomyomas. There was insufficient DNA in 1, whereas 8 of 17 (47%) had a mutation, 6 (75%) being in TSC2. In 4 of 18 cases, a mutation was detected in the fetus for the first time despite a parent known to have TSC. Conclusion The value and utility of prenatal diagnosis of TSC by DNA analysis was demonstrated by the results in this series of 50 pregnancies in women at risk of having affected offspring. A family history of TSC or detection of fetal cardiac rhabdomyoma should prompt genetic evaluation and counseling of parents and the option of prenatal diagnosis.