Complications
Feeding difficulties occur in 77% of infants, and range from mild (e.g., poor sucking reflex) to severe, requiring tube-feeding.[29][30][31]
The feeding difficulties are usually related to hypotonia (low muscle tone) and poor coordination of oral musculature. However, immature gut motility and delayed GI motor development have been documented in some cases.[31]
Typically, the period of failure to thrive is self-limited, although poor weight gain may persist for up to 18 months.[30]
Although rare, juvenile myelomonocytic leukemia (JMML) and, less commonly, acute lymphoblastic leukemia (ALL) have been reported, and may be linked to particular mutations in PTPN11.[2][80] However, routine monitoring has not been advocated.
Earlier onset and milder presentation than sporadic JMML, with spontaneous remission, is suggestive of Noonan syndrome-associated JMML.
Neuroblastoma, low grade glioma and rhabdomyosarcoma are all reported in a handful of individuals with NS, but epidemiological studies are needed to estimate precise cancer risk.[81][82]
Regular physical exam and complete blood counts can be performed in children with Noonan syndrome if specific high-risk PTPN11 or KRAS mutations are present.[83]
Among the most common features of NS, and observed in up to 95% of cases.
They include strabismus (crossed eyes), refractive errors (astigmatism, myopia, hypermetropia), amblyopia (lazy eye), nystagmus (involuntary eye movement), and ptosis.
Anterior segment changes, such as prominent corneal nerves, anterior stromal dystrophy, cataracts, and panuveitis, are reported in approximately 66% of cases.
Fundal changes are less frequent, and include optic head drusen, optic disk hypoplasia, colobomas, and myelinated nerves.[29][30][43]
Children should have a thorough ophthalmology evaluation, to ensure that the problems are detected early and that they are treated accordingly.
Mild cognitive impairment is found in up to 33% of cases, and IQ ranges from 64 to 127.[29][34]
Specific visual-constructional problems, verbal-performance discrepancy, and language delay or impairment may be present even when IQ is normal.[29][35][36][37][60][39]
Children with NS have a specific impairment in the global processing of visuospatial information.[38]
Adults with NS may experience specific difficulties in information processing, but this rarely has an impact on cognition.[39]
Seizures are described in up to 10% of people with NS, with an average onset at 11 years of age.[30]
Multiple giant cell lesions (also known as cherubism) are rare complications of several disorders of the Ras/MAPK pathway, including NS, cardio-facio-cutaneous syndromes, and neurofibromatosis type 1.[84]
They are generally found in the mandible and would be detected by examination of the jaw, noting increased size or asymmetry, or by dental radiographs.
The lesions are sufficiently rare that routine monitoring is not recommended.
Polyarticular pigmented villonodular synovitis is even more unusual.
Scoliosis, pes planus, muscle weakness, and pectus anomalies are common.
A range of autoantibodies and associated autoimmune diseases have been reported in people with Noonan syndrome or related disorders, which suggest involvement of different genes of the Ras/MAPK pathway in immunity.[27]
Conditions reported include systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, primary antiphospholipid syndrome, autoimmune hepatitis, vitiligo, and autoimmune thyroiditis.[27]
Specialist referral should be considered for investigation and treatment. [27]
Use of this content is subject to our disclaimer