Page 15 - Clinical variability in Noonan syndrome with emphasison ear and eye

Musculoskeletal abnormalities, neurologic features, and motor development
Chest wall anomalies have a prominent role in diagnosing Noonan syndrome. In the clinical scoring system a pectus excavatum or pectus carinatum are major signs and a broad thorax is a minor sign (16). Pectus carinatum is superiorly and pectus excavatum is inferiorly seen in Noonan syndrome, together described in up to 95% of the patients (14). Spinal and vertebral deformities are seen including scoliosis. Other orthopedic features include talipes equinovarus, radio-ulnar synostosis, joint contractures, and hyperextensible joints (14-16,47).
Difficulties and delay in motor performance and hypotonia are frequently reported in Noonan syndrome. The average age for sitting unsupported is ten months and walking 21 months (14). Developmental coordination disorders including clumsiness are described in up to 50% (48). Impaired manual dexterity is also described and is correlated with nonverbal and verbal intellectual functions (49). Chronic pain (joints, extremities, muscles) is described in more than 50% of the Noonan syndrome patients (46,50). Neurologic problems and brain abnormalities are described seldom. Arnold- Chiari malformation and hydrocephaly are mentioned in literature. Other neurologic features are epilepsy, peripheral neuropathy and craniosynostosis (14,15,51).
Genitourinary problems
In up to 80% of the boys cryptorchidism, both unilateral and bilateral, is described and surgical orchiopexy is required (14). Male gonadal dysfunction is reported and suggested to be due to Sertoli cell dysfunction (52). Puberty in male can be delayed or inadequate and is associated with deficient spermatogenesis and puberty in female can be delayed but a normal fertility is expected (53).
Lymphatic issues
Lymphatic dysplasia is a feature in the clinical scoring system. Lymphatic dysplasia, hypoplasia or aplasia is described in approximately 20% of the Noonan syndrome patients and it can occur in all ages (54). Peripheral lymphedema is the most common manifestation. Different lymphatic issues are described in a few Noonan syndrome patients, including hydrops, chylous pleural effusion, pulmonary and intestinal lymphangiectasis and anomalous lymphatic vessels (31,33).
Hematology and oncology
Bleeding disorders are reported in 30-65% of the individuals with Noonan syndrome (14,55). Most have a positive bleeding history with mild symptoms of epistaxis, excessive bruising or bleeding with surgery. Different etiologies are described including platelet function defect, thrombocytopenia, Von Willebrand disease, and coagulation factor deficiency (56). Special care is required for surgery in Noonan syndrome patients.
INTRODUCTION
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