Discussion
Phenotypically Noonan syndrome especially in female share similar features with Turner syndrome such as short stature, webbed neck, wide space nipple, mental retardation, urogenital and cardiac abnormalities, and craniofacial dysmorphism. Karyotyping is the only investigation on the basis of which we can differentiate between these two conditions. [5] Noonan syndrome is a genetic condition and the common mutations involve are PTPN11, SOS1, RAF1, KRAS, NRAS, and BRAF genes. Among these mutations, PTPN11 gene mutations account for about 50%, SOS1 gene mutation for 10%–15%, and RAF1 gene mutation for 5%–10% of Noonan syndrome. KRAS, NRAS, and BRAF genes account for a relatively small percentage of Noonan syndrome. [6, 7] Diagnosis of Noonan syndrome can be made either by genetic testing or clinical diagnostic criteria. Both are equally specific because 25 percent of the genetic testing for Noonan syndrome is nonconclusive. The scoring system for the diagnosis of Noonan syndrome was developed by Van der Burgt et al in 1997 which are made of 6 major features and 6 minor features. According to this criteria, Noonan syndrome can be diagnosed with typical facial features plus 1 major or 2 minor characteristics or suggestive facial features plus 2 major or 3 minor signs. [8] Our patient had typical facial features with 1 major criterion i.e. short stature (below 3rd percentile). The following shows table shows the scoring system for Noonan syndrome (Table.2)
Differential diagnoses of Noonan syndrome include Turner syndrome (45, XO), Cardio-Facio-Cutaneous (CFC) syndrome, Costello syndrome, Neurofibromatosis type 1 (NF1), and LEOPARD syndrome. Syndromes that are characterized by facial dysmorphology, short stature, and cardiac defects may sometimes be difficult to differentiate from NS, notably Williams syndrome and Aarskog syndrome. As the syndrome has a wide spectrum of disorders, patients with Noonan syndrome have to undergo hematological investigations, karyotyping and mutation analysis cardiac investigations, and Assessment of development (IQ, Identifying any delays, mental retardation). [9,10]
Previously a study has shown the association between hypothyroidism and Noonan’s syndrome although few studies report autoimmune thyroiditis the cause is unknown, but factors that may predispose to the condition include genetics, high iodine consumption, and age. Vesterhus P et al in a study showed thyroid antibodies were found to be more common in Noonan syndrome, but hypothyroidism is not more common in Noonan syndrome compared to the general population. [11,12] There is no single treatment available for Noonan syndrome, a multidisciplinary approach is needed to address the patient’s concerns and to treat the complications or associated conditions.