Previously unrecognized genetic mutation may underlie some cases of sudden infant death

Identification of genetic mutation in a healthy infant who survived a sudden cardiac arrest at home underscores the need for genetic testing, physicians report in Heart Rhythm Case Reports

A previously healthy infant who suffered aborted sudden cardiac death was found to have a de novo genetic mutation in the SOS1 gene. Such mutations are typical of Noonan syndrome and suggests the syndrome may be a cause of unrecognized 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 had none of the usual structural cardiac findings of Noonan syndrome, such as damaged heart valves or abnormally thick heart muscle tissue. However, they may appear later in development.

'Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis and assessing risk to family members,' said co-authors Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, of the 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 female infant did not awaken as usual for her morning feeding; her mother found her limp, pale and suffering from breathing difficulties. EMS arrived quickly and found the infant pulseless. Three shocks from a defibrillator were needed to restore sinus rhythm. On presentation to the ICU, the patient had incessant, rapid episodes of ectopic atrial tachycardia. This potentially serious arrhythmia is an unusual finding in the neonatal postarrest period. Normal cardiac function was restored after medication and treatment. An echocardiogram revealed a structurally normal heart with normal valves and there was no ventricular hypertrophy, dilation, or noncompaction noted. Other tests were normal.

Apical 4-chamber at (A)end diastole and (B) end systole at initial presentation. M-mode from (C) parasternal short axis view at presentation. Ejection fraction was 48.7% and shortening fraction 24.8%, which improved to 63.3% and 38.5%, respectively, at 1 month. There was normal valve morphology and function without evidence of ventricular hypertrophy, dilation, or noncompaction (Credit: Heart Rhythm Case Reports).

The genetics team was consulted and a standard family history was obtained. An older sibling had no known medical conditions. The child's paternal grandfather had died of a presumed heart attack in his 50s, but no autopsy had been performed. There was no family history of congenital heart disease, sudden death, development delay, or other conditions. A next-generation sequencing panel revealed the likely pathogenetic 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, dermatologic and neurocognitive findings. Cardiac phenotypes are also common. SOS1-mediated Noonan syndrome can have a mild phenotype, which may not be apparent until the child becomes older, when neurocognitive findings become more noticeable, as seems to be the case with this patient.

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

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Notes for editors
The article is 'Ventricular fibrillation due to a likely pathogenic SOS1 variant: An unrecognized etiology of infantile sudden death?' by Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO (https://doi.org/10.1016/j.hrcr.2021.06.010). It appears in Heart Rhythm Case Reports, volume 7, issue 8 (August), published by Elsevier.

The article is freely available to all at https://www.heartrhythmcasereports.com/article/S2214-0271(21)00134-2/fulltext.

For additional information contact Jane Grochowski at +1 406 542 8397 or [email protected]. Journalists who wish to interview the case report authors should contact Lisa Augustine, Media Relations Manager, Children's Mercy Kansas City, at +1 816 302 0197 or [email protected].

About Heart Rhythm Case Reports
Heart Rhythm Case Reports is an official Journal of the Heart Rhythm Society. It is an open access companion journal to the respected Heart Rhythm. It provides rapid online electronic publication of the most important current case reports, illustrations, and educational vignettes in the field of cardiac arrhythmias and electrophysiology. The Journal publishes case reports and series devoted to the diagnosis and treatment of heart rhythm disorders, as well as the electrophysiology of the heart and blood vessels. All articles are peer-reviewed. www.heartrhythmcasereports.com

About the Heart Rhythm Society
The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal healthcare policies and standards. The Heart Rhythm Society is the preeminent professional group representing more than 6,500 specialists in cardiac pacing and electrophysiology from more than 70 countries. www.HRSonline.org

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