Noonan syndrome – a new survey

Abstract

Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway are responsible for NS and other related disorders. Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients. Due to the high number of genes associated with NS and other RASopathy disorders, next-generation sequencing is the best choice for diagnostic testing. Patients with NS also have higher risk for leukemia and specific solid tumors. Age-specific guidelines for the management of NS are available.

Molecular and phenotypic spectrum of Noonan syndrome in Chinese patients

“… NGS‐based genetic testing is particularly useful for clinicians when the phenotypes of sporadic patients are ambiguous or complicated. Phenotypic heterogeneity is common in patients diagnosed with NS, which increases the difficulty of clinical differentiation and diagnosis . Our group has confirmed the clinical utility of NGS‐based testing in Chinese patients with genetic disorders, which includes patients with suspected NS …”

“…Phenotypic heterogeneity is common in patients diagnosed with NS, which increases the difficulty of clinical differentiation and diagnosis. 9,10 Our group has confirmed the clinical utility of NGSbased testing in Chinese patients with genetic disorders, which includes patients with suspected NS. 11 Here, NGS-based genetic testing was applied to identify pathogenic variants in 103 unrelated Chinese patients to assist with the diagnosis of Noonan syndrome (NS) in a single center over a short period of time (2016)(2017)(2018).Detailed clinical information was collected and analyzed, including pregnancy and perinatal period, facial images, growth/development, physical examination, echocardiography, routine blood tests, biochemical testing, a gastrointestinal ultrasonograph, an ultrasound of the urinary system, and hearing and eye examinations, to elucidate the possible underlying genotype-phenotype correlations.…”

Prevalence of Noonan spectrum disorders in a pediatric population with valvar pulmonary stenosis

“…14 NS displays significant genetic heterogeneity; at least nine genes are known to cause NS, with PTPN11 being the most common, although at least 17 genes in the RAS-MAPK signaling pathway have been associated with related RASopathies and Noonan spectrum disorders (NSD) which share a considerable phenotypic overlap. [15][16][17][18][19][20][21][22][23][24][25][26][27][28] Sharland et al reported an average age at diagnosis of 9 years and indicated that diagnosing patients at an earlier age would be beneficial. 8 A more recent study reported an average age at diagnosis of 7 years.…”

Cleft palate and hypopituitarism in a patient with Noonan‐like syndrome with loose anagen hair‐1

“…Individuals with NSLH1 are more likely to have intellectual disability, relative macrocephaly, sparse/loose anagen hair, and growth hormone deficiency (GHD) compared to individuals with Noonan syndrome (NS) caused by mutations in other genes. The clinical features of 84 patients with NSLH1 have been described (Table ) (Bader‐Meunier et al, ; Capalbo, Melis, et al, ; Capalbo, Scala, et al, ; Choi et al, ; Cordeddu et al, ; Ekvall, Hagenäs, Allanson, Annerén, & Bondeson, ; Ferrero et al, ; Garavelli et al, ; Gargano et al, ; Gripp et al, ; Hoban, Roberts, Demmer, Jethva, & Shephard, ; Kane et al, ; Komatsuzaki et al, ; Lo, Wang, Wong, & Lee, ; Mazzanti et al, ; Mazzanti et al, ; Şimşek‐Kiper et al, ; Tafazoli, Eshraghi, Koleti, & Abbaszadegan, ; Takenouchi et al, ; Tartaglia, Zampino, & Gelb, ; Tosti et al, ; Tosti et al, ; Tosti & Piraccini, ; Zmolikova et al, ). With the possible exception of one patient with unusual but not well‐defined palatal anatomy (Kumar, Chandar, Koduri, & Sankireddy, ), posterior cleft palate (CP) has not been reported in individuals with NS or with NSLH (Cao, Alrejaye, Klein, Goodwin, & Oberoi, ; Mallineni, Yung Yiu, & King, ).…”