Sudden infantile death associated with a de novo genetic mutation of the SOS1 gene

A previously healthy infant who suffered sudden aborted heart death was found to have Again genetic mutation in the SOS1 uncomfortable. Such mutations are typical of Noonan syndrome and suggest that the syndrome may be an unrecognized cause of sudden death in infancy. The case is reported in Heart Rhythm Case Reports, an official journal of the Heart Rhythm Society, published by Elsevier.

Noonan syndrome is a genetic disorder that affects normal development, causing skeletal, cardiac and neurocognitive delays. The infant did not have any of the usual structural heart signs of Noonan syndrome, such as damaged heart valves or abnormally thick heart muscle tissue. However, they can appear later in development.

Genetic testing in cases of unexplained abortion or sudden cardiac death, even in previously healthy children, can be useful in making a diagnosis, determining prognosis, and assessing risk to family members. ”

Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, co-authors of Ward Family Heart Center, Children’s Mercy Kansas City and University of Missouri School of Medicine Kansas City, Kansas City, MO, USA

A two-month-old baby girl did not wake up as usual for her morning feed; her mother found her limp, pale and suffering from breathing difficulties. EMS arrived quickly and found the infant without a pulse. Three shocks from a defibrillator were required to restore sinus rhythm. On presentation to the ICU, the patient had incessant and rapid episodes of ectopic atrial tachycardia. This potentially serious arrhythmia is an unusual finding in the post-arrest neonatal period. Normal heart function was restored after medication and treatment. An echocardiogram revealed a structurally normal heart with normal valves, and no ventricular hypertrophy, dilation, or non-compaction was noted. The other tests were normal.

The genetics team was consulted and a standard family history was obtained. An older brother had no known medical problem. The child’s paternal grandfather had died of a suspected heart attack in his 50s, but no autopsy had been performed. There was no family history of congenital heart disease, sudden death, developmental delay, or other conditions. A next-generation sequencing panel revealed the probable pathogenic variant of the SOS1 gene associated with Noonan syndrome.

Noonan syndrome belongs to a family of related genetic syndromes known as RASopathies with overlapping phenotypic features including skeletal, dermatological and neurocognitive findings. Cardiac phenotypes are also common. SOS1Mediated Noonan syndrome may have a mild phenotype, which may not be apparent until the child grows older, when the neurocognitive findings become more noticeable, as appears to be the case with this patient.

“To the best of our knowledge, our case is the first reported ventricular fibrillation arrest associated with RASopathy in the absence of the structural cardiac phenotypes typical of hypertrophic cardiomyopathy or pulmonary stenosis. In the case of this patient, it will allow monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows, ”observed Dr Follansbee and Dr Malloy-Walton. “Further research is essential to uncover the underlying causes of sudden unrecognized deaths in infants.”