Noonan's Syndrome – History and Present
The genetically determined syndrome linking congenital heart defect with a typical facial phenotype is named after Jacqueline Noonan, a pediatric cardiologist who practiced in the second half of the 20th century. She was the first to recognize and describe it. In the following text, we will briefly introduce it and discuss the circumstances of its discovery.
Six Decades with Pediatrics
Jacqueline Noonan was born on October 28, 1928, in Burlington, Vermont, USA. At the age of five, she decided to become a doctor and work with children. From the age of 28, she dedicated herself to cardiology as a certified pediatrician until her retirement in 2007, although she remained active even after. She passed away recently, on July 23, 2020, at the age of nearly 92 years.
Discovery Through Diligent Work
While working at the University of Iowa, where Dr. Noonan specialized in cardiac catheterizations, she noticed that some pediatric patients with congenital heart defects also had other congenital anomalies. Being very meticulous and systematic, she set up a system of cards where she noted down birth data, family history, and clinical characteristics of each patient. She reviewed the cards of 835 children she observed from July 1959 to June 1961 and found that in cases of pulmonary valve stenosis, patients often had a similar – typical – facial appearance.
“Male Turner Syndrome”
She presented her findings at a pediatric conference in Cincinnati in 1962, where she first described the typical phenotype of patients as so-called male Turner syndrome with a normal karyotype: short stature, broad nasal bridge, mild mental retardation, ptosis of the eyelids, undescended testes, and skeletal malformations. After six more years of research, she published an article adding exophthalmos, low-set ears, curly hair, short neck, elbow deformity (cubitus valgus), and skin fold on the neck (pterygium colli) to the classic symptoms.
It is presumed that the first documented patient with Noonan syndrome was a 20-year-old Estonian in 1883 based on clinical phenotype.
The Eponym's Origin
This newly described syndrome still lacked a name and was described as “broad nasal bridge with Turner-like phenotype.” The name gradually came about thanks to Dr. John Opitz, whom Dr. Noonan had taught at the university while he was still a student. He later frequently used the term “patient with Noonan's syndrome,” which no one knew. It was an unofficial term, and Jacqueline Noonan herself did not use it until 1972 when, after presenting the syndrome at a pediatric endocrinology conference, a doctor from the audience allegedly asked, “And who is Noonan anyway?” The future long-time chairwoman of the American Pediatric Society stood up and said, “I am.”
Genetic Basis
From the beginning, Dr. Noonan hypothesized a genetic basis for this condition based on her observations. However, it wasn't until the development of molecular genetics that a mutation in the PTPN11 gene, located on the long arm of chromosome 12, significant for Ras-MAPK kinase signaling, was identified in 2001. Further research revealed that the condition is not caused by pathogenic variants of a single gene, and in subsequent years, several other causal genes were discovered.
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Source: Miller B. S. The history of Noonan syndrome. Ped Endocrinol Rev 2019; 16 (Suppl. 2): 424–427, doi: 10.17458/per.vol16.2019.m.historynoonan.
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