In a review of the spectrum of genetic diseases in Bahrain, Al-Arrayed (1999) found an increased rate of families with Noonan syndrome. In 2006, Al-Arrayed (Personal communication, Dubai, 2006) reported 10 cases of NS from Bahrain; including four Bahraini boys and six Pakistani girls (3 alive and 3 deceased). One of the Bahraini boys was a sporadic case, while the other three were siblings of one family. It was conjectured that the father could be the transmitting parent as he had ptosis, but was normal mentally. A changing phenotype with age was found to manifest in this family (Allanson et al., 1985). The 2- year old boy had more severe edema, ptosis and a round face whereas the eldest boy had EEG abnormality and seizures.

[Al-Arrayed SS. Review of the spectrum of genetic diseases in Bahrain. East Medit Health J. 1999; 5(6):1114-20.]

Aglan et al. (2003) compared the clinical features of 14 Egyptian patients (eight males and 6 females) diagnosed with NS, with patients diagnosed with CFC syndrome. Analysis involved three generation pedigree construction, clinical examination, anthropometric and IQ measurements, cytogenetic studies, echocardiography, and ultrasound examination. Except for one case, where two of the patient's cousins were reported to have clinical symptoms of NS, all other cases were sporadic. Parental consanguinity was observed in 42.8% of the cases. Aglan et al. (2003) showed that in the cases they studied, clinical features could be used to differentiate between NS and CFC. The important features which were found in a significantly higher frequency in NS cases, compared to CFC were antimongoloid staining (57% NS, 17% CFC), ptosis (50% NS, 17% CFC), neck webbing (71% NS, absent in CFC), and shieldchest (64% NS, 17% CFC). On the other hand, features like gastrointestinal problems (7% NS, 66% CFC), bitemporal constriction (66% CFC, absent in NS), short nose (29% NS, 100% CFC), sparse hair (absent in NS, 100% CFC), and relative macrocephaly (7% NS, 100% CFC) were present in higher frequencies in CFC cases. One of the patients with NS had factor XI deficiency. Undescended testicles and hypogonadism were observed in three of the NS male patients. Mental retardation was observed in 50%, and absolute microcephaly in 14% of the cases. Aglan et al. (2003) proposed that comprehensive clinical examination and scoring indices are important towards identifying cases of NS, and differentiating them from other symptoms with overlapping manifestations.

[Aglan MA, Afifi HH, el-Kotoury AIS, Ashour AM. Noonan and cardiofaciocutaneous syndromes: clinical evaluation of overlapping manifestations. J Arab Child 2003; 14(5):499-513.]

Mansour et al. (2005) conducted a retrospective study of 240 consecutive patients with congenital heart disease. In all, 105 syndromic subjects included the velocardiofacial syndrome (18), Down's syndrome (17), CHARGE association (6), DiGeorge syndrome (5), Williams syndrome (3), Edwards syndrome (3), Noonan syndrome (3), VACTERL association (2), and Patau syndrome (trisomy 13) (2).

Soliman et al. (1998) compared auxological and endocrine data from 12 prepubertal children (3 males, 9 females) with Noonan syndrome (NS) with those of 15 children with constitutional short stature (CSS), 20 children with partial GH deficiency (GHD), and 6 children with Turner syndrome (TS). Four children with NS were treated with human growth hormone (hGH) (n = 4) (25 units/m2 week, divided on daily s.c. doses). In children with NS, the peak serum GH response to clonidine (5.4 +/- 2.7 ug/L) and glucagon (7.4 +/- 3.4 ug/L) were significantly lower than those for children with CSS (14.8 +/- 3.4 and 12.8 +/- 2.8 ug/L respectively). Nine out of the 12 (75%) children with NS did not mount normal GH peak (10 ug/L or more) after provocation. The 12-h integrated GH secretion in the 3 children with NS who had normal GH response to provocation (2.7 +/- 0.7 ug/L) was markedly lower compared to that for children with CSS (6.7 +/- 1.2 ug/L). On the other hand, the serum insulin-like growth factor-1 (IGF-I) concentrations were lower in children with NS (67 +/- 32 ng/ml) vs CSS (165 +/- 35 ng/ml), but not different from those for GHD children (59 +/- 33 ng/ml). In 4 children with NS, hGH therapy for a year increased height growth velocity from 4.1 +/- 0.3 cm/yr to 7.4 +/- 0.6 cm/yr and height standard deviation score (Ht SDS) from -2.2 +/- 0.6 to -1.45 +/- 0.3. This growth acceleration was accompanied by an increase in IGF-I concentration (from 52 +/- 21 ng/ml to 89 +/- 25 ng/ml). Soliman et al. (1998) concluded that in children with NS there exists a defect of the GH secretion and suggested that GH therapy has an important role in the management of their short stature.

Sawardekar (2005) conducted a study to establish the prevalence of major congenital malformations in children born during a 10-year period in an Omani hospital in Nizwa. Of the 21,988 total births in the hospital, four children were born with Noonan Syndrome. Sawardekar (2005) hinted for a possible genetic contribution in these children.