Noonan syndrome (NS) is a multiple congenital anomaly syndrome inherited in an autosomal dominant pattern. Noonan syndrome is characterized by dysmorphic facies, short stature, ear abnormalities, cryptorchidism, ocular abnormalities, cardiovascular anomalies, cubitus valgus, webbed neck, and cutaneous and hair abnormalities.
Despite the presumed genetic link, the exact etiology is unknown; it has been hypothesized that NS patients have a genetic defect which alters prenatal development of the lymphatic vessels and disrupts tissue migration and organ placement during a critical period. A candidate gene for this disorder has been mapped to 12q22-qter. Autosomal dominant inheritance with variable expression has been well documented, but many cases appear to be sporadic. Recent research suggests that parent-to-child transmission is more common than originally assumed.
Noonan syndrome is second only to Downs syndrome as one of the most common syndromes associated with congenital heart disease, accounting for 1.4% of children with cardiac defects and 17% of children undergoing surgery for pulmonary stenosis.
Growth retardation is a consistent feature of NS. Although children are not typically growth hormone deficient, a minority may have suboptimal growth hormone levels. The use of growth hormone therapy in NS is controversial and the subject of numerous current and previous research studies.
Developmental delay is frequent, and mild mental retardation, although relatively common (25%), is not constant. Children with NS have strengths in non-verbal reasoning, verbal comprehension, social judgment, and visual motor abilities. Specific weaknesses are found in spatial knowledge and planning abilities. Frequently, NS-affected individuals demonstrate problems with organization, memorization, and concentration. Studies show a wide range of IQ and a variable pattern of verbal-performance discrepancy.
The phenotype in Noonan syndrome changes consistently and predictably between infancy and adulthood. The differential diagnosis for patients with NS is extensive and includes XO/XX mosaicism, fetal hydantoin syndrome, fetal mysoline syndrome, Watson syndrome, cardiofaciocutaneous syndrome, Costello syndrome, and fetal alcohol syndrome have all been considered in patients with this phenotype.
Marked phenotoypic variability makes Noonan syndrome difficult to recognize in the newborn, and the changing phenotype with time often makes mild Noonan syndrome difficult to recognize in adults. Karyotype is normal; accurate prenatal diagnosis is not available, and no diagnostic tests exist. Diagnosis is purely clinical and subjective at present. In addition, maternal use of alcohol or other teratogens and identification of other chromosomal abnormalities must be considered to rule out competing diagnoses. Noonan syndrome should be suspected in infants who present with hypertrophic cardiomyopathy, (particularly if they also have valve dysplasia) and neonatal edema of the dorsum of hands and feet.
To help in making a diagnosis, Noonan (1994) indicates that the following features are typically present, though often difficult to discern in newborns: sloping forehead; thick ears which may be posteriorly positioned; hypertelorism with down-slanting of the palpebral fissures; deep-set groove of the upper lip; occasional retrognathia; marked edema of the neck, with excess skin on the back of the neck; relatively enlarged head from infancy through age 2; flat cheekbones with prominent, round eyes; depressed nasal bridge; stocky body, with chest deformities that become more prominent with age; and a short neck.
Note: These considerations are in addition to the normal medical care provided to an individual without Noonan syndrome. All recommendations can be addressed through clinical examination by the primary care provider, unless otherwise noted.
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van der Burgt, I., Thoonen, G., Roosenboom, N., Assman-Huylsmans, et al. (1999). Patterns of Cognitive Functioning in School-aged Children with Noonan Syndrome Associated with Variability in Phenotypic Expression. The Journal of Pediatrics, 135(6), 707-713.
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