Can Noonan Syndrome Cause Fetal Growth Restriction?
Yes, Noonan syndrome can cause fetal growth restriction, though it is not a typical or common presentation during fetal life, and growth failure is predominantly a postnatal phenomenon in this condition.
Growth Pattern in Noonan Syndrome
The growth disturbance in Noonan syndrome follows a characteristic temporal pattern that is important to understand:
- Birth weight is typically normal in infants with Noonan syndrome, indicating that intrauterine growth is generally preserved 1, 2.
- Growth failure is mainly postnatal in character, dominated by slow maturation and delayed puberty, with the postnatal early decline appearing to be an intrinsic part of the syndrome 3.
- Adult heights average approximately -2 standard deviations below the mean, but this results from cumulative postnatal growth failure rather than fetal growth restriction 3.
Prenatal Manifestations When Present
While FGR is not the hallmark of Noonan syndrome, when prenatal abnormalities do occur, they typically manifest as:
- Third-trimester findings including polyhydramnios, skin edema, hydrothorax, and cardiac malformations rather than growth restriction 1.
- First and second-trimester ultrasounds are usually normal, with the diagnosis of Noonan syndrome typically suggested only during the third trimester or after birth 1.
- Transient nuchal translucency or cystic hygroma may be seen in early gestation but often resolve spontaneously 1.
Differential Diagnosis Context
Noonan syndrome is listed among genetic and teratogenic conditions to be considered in the differential diagnosis of fetal alcohol spectrum disorders (FASD), which do present with growth restriction 4. However, this inclusion reflects overlapping dysmorphic features rather than FGR being a primary feature of Noonan syndrome itself.
When evaluating early-onset FGR, chromosomal abnormalities account for approximately 6.4% of cases, and genetic syndromes should be considered 5. However, Noonan syndrome would be an uncommon genetic cause of isolated FGR given its predominantly postnatal growth pattern 3, 6.
Clinical Implications
- If a fetus presents with isolated FGR without structural abnormalities, Noonan syndrome would be a low-probability diagnosis 1, 3.
- If a fetus presents with third-trimester polyhydramnios, cardiac defects (especially pulmonary stenosis), hydrothorax, or nuchal abnormalities, Noonan syndrome should be considered even if growth is normal 1.
- Chromosomal microarray analysis should be offered when FGR is detected with fetal malformation or when unexplained isolated FGR is diagnosed at <32 weeks gestation 5.
Mechanism of Growth Delay
The growth failure in Noonan syndrome appears to result from partial growth hormone insensitivity at a post-receptor level and possible derangements in the RAS/MAPK signaling pathway, rather than from placental insufficiency that would cause fetal growth restriction 7.