Akademik Veri Yönetim Sistemi
Türk Alman Jinekoloji Kongresi, Antalya, Türkiye, 23 - 27 Nisan 2025, cilt.1, sa.1, ss.86-87, (Tam Metin Bildiri)
Case Report: Prenatal diagnostic challenges in a fetus with
Noonan syndrome despite negative PGT: a case of de novo PTPN11 mutation
Yavuz Yılmaz1 , Osman İnce2 , Cem Dağdelen2 , Tuğçe Tunç
Acar2 , Gizem Pınar2 , Ömer Faruk Öz1 , Can Dinç1 , İbrahim İnaç Mendilcioğlu2
1 Department of Obstetrics and Gynecology, Akdeniz
University Hospital, School of Medicine,Antalya,Turkey
2 Department of Perinatology,Akdeniz University Hospital,
School of Medicine,Antalya,Turkey
INTRODUCTION: Noonan syndrome is a relatively common
autosomal dominant genetic disorder with an estimated incidence of 1 in 1,000
to 2,500 live births. It is classified within the group of RASopathies, a
family of syndromes caused by mutations affecting the RAS-MAPK signaling
pathway. The most frequently involved gene is PTPN11.Clinically, it is
characterized by a variable phenotype including short stature, facial
dysmorphism, congenital heart defects, developmental delay, and lymphatic
anomalies. Prenatal diagnosis of Noonan syndrome is challenging due to the
nonspecific and variable nature of sonographic findings. As the pregnancy
progresses, additional anomalies may become apparent, such as polyhydramnios,
fetal hydrops, pleural effusions, cardiac defects, and growth restriction.
Structural cardiac anomalies, particularly hypertrophic cardiomyopathy or
septal defects, are common and often serve as diagnostic clues. Craniofacial
features like hypertelorism, micrognathia, and a depressed nasal bridge may
also be noted on detailed anatomical survey or ultrasonography (USG).
CASE: A 32-year-old gravida 3, para 2 woman was referred to
our perinatology clinic due to a history of two neonatal deaths, both resulting
from multiple congenital anomalies. Her first pregnancy ended with the neonatal
death of a female infant on day 7, born at 35 weeks via cesarean section. The
second pregnancy also ended in neonatal death on day 3; genetic analysis of the
fetus identified a homozygous ETFB variant, classified as a Variant of
Uncertain Significance, consistent with a potential diagnosis of Glutaric
Aciduria Type IIB. Both parents were heterozygous carriers of the same variant.
The current pregnancy was conceived via IVF following preimplantation genetic
testing (PGT) to exclude the ETFB variant. Despite PGT, new sonographic
anomalies prompted a recommendation for amniocentesis to confirm the genetic
status of the fetus; however, the parents declined all invasive testing. Serial
detailed USG examination revealed multiple findings, including mild lateral
ventriculomegaly (12mm)(fig.1), obliterated cavum septum pellucidum (fig.2),
micrognathia, hypertelorism, leftward cardiac axis deviation and concentric
myocardial hypertrophy (fig.3), a small inlet-type ventricular septal defect
(VSD), renal pelvis dilatation (r6 mm). Fetal magnetic resonance imaging (MRI)
was performed due to ventriculomegaly, and no additional pathological findings
were identified. At 37w2d, an elective cesarean section was performed due to
previous cesarean delivery and contraction pain. A male infant was delivered in
breech presentation, 3350 grams, apgar scores 6/7. Physical examination
revealed, including micrognathia and hypertelorism. The newborn was admitted to
the NICU for further evaluation. Postnatal whole exome sequencing (WES)
identified a pathogenic variant in the PTPN11 gene, confirming a diagnosis of
Noonan syndrome. CONCLUSION: In this case emphasizes the role of detailed
prenatal imaging in raising suspicion for Noonan syndrome, even in the absence
of classic first-trimester markers. It also highlights the limitations of PGT
when underlying genetic complexity or de novo pathogenic mutations are
involved. Despite the absence of early nuchal thickening and the presence of
normal first-trimester screening, progressive structural anomalies raised
prenatal suspicion.
Keywords: Noonan Syndrome, PGT, prenatal diagnosis,
RASopathies, fetal anomaly, Prenatal ultrasonography