KENT, England — In a rare and tragic sequence of events, a father and later his son died from cardiac complications linked to an underlying genetic disorder known as Alagille Syndrome (ALGS). The case illustrates how inherited conditions can silently elevate cardiac risk across generations and highlights the importance of genetic evaluation in families with unexplained cardiac issues.
In 2017, Jason Selvey, 47, died suddenly from cardiac arrest after reporting mild symptoms. Six years later, his son Daniel, then 24, experienced a similar fatal heart event. Genetic testing within the family ultimately identified ALGS as the common underlying factor in both deaths. Prior to Daniel’s diagnosis and sudden death, his cardiac issues had been investigated across multiple clinical settings without a definitive unifying diagnosis.
Amber Selvey told People that her husband, Jason, and their son, Daniel, died six years apart and that there was no known family history of Alagille syndrome before genetic testing was carried out.
Alagille syndrome can be very difficult to recognize because symptoms vary widely and often appear in isolation rather than as one clear condition.Amber Selvey, Wife of Jason Selvey
ALGS is a multisystem autosomal dominant genetic disorder. It arises primarily from mutations in the JAG1 gene and, less commonly, the NOTCH2 gene. These genes play a fundamental role in the Notch signaling pathway, which regulates embryonic development of the heart, liver, and other organs.1
The clinical manifestations of ALGS vary widely, even within the same family. Typical features include:
Abnormal development or paucity of bile ducts in the liver.
Structural heart abnormalities, such as narrowing of pulmonary arteries or defects in heart valves.
Skeletal anomalies like butterfly-shaped vertebrae.
Eye irregularities and distinctive facial features.
Cardiac involvement is a major component of ALGS and can include pulmonary artery stenosis, tetralogy of Fallot, and other congenital heart defects, contributing significantly to morbidity and mortality.2
Amber Selvey, Wife of Jason Selvey told PEOPLE magazine,
Heart problems are also common and may include narrowing of blood flow from the heart to the lungs (pulmonary stenosis), heart murmurs, or more complex defects such as tetralogy of Fallot. In my eldest son’s case, he had aortic valve stenosis and a bicuspid aortic valve, which was later found at post-mortem to be a unicuspid valve, which is extremely rare. When cardiac issues occur without obvious liver disease, the underlying genetic link can be missed.Amber Selvey, Wife of Jason Selvey
ALGS is inherited in an autosomal dominant manner, meaning an affected individual has a 50% chance of passing the condition to each child. However, the degree of manifestation varies widely; some carriers exhibit only subtle signs while others develop severe disease.3,5
This variable expressivity explains why some family members with the same gene mutation may have drastically different health outcomes. It also underscores why ALGS can go unrecognized across generations until multiple affected individuals emerge.
The case highlights several clinical lessons:
Family History: Unexplained cardiac deaths or congenital heart conditions in relatives should prompt consideration of genetic syndromes such as ALGS.
Early Genetic Counselling: In families with multiple members exhibiting cardiac or related systemic conditions, referral for genetic counselling and testing can identify at-risk individuals.
Multidisciplinary Care: Management of ALGS benefits from coordinated input across cardiology, genetics, hepatology, and primary care to monitor and address multisystem involvement.3,4
The Selvey family’s experience underscores the complexity of inherited cardiac conditions like ALGS. Recognizing patterns within family histories and integrating genetic evaluation into clinical practice can improve early detection and management of individuals at risk for serious cardiac outcomes.
References
1. Diaz-Frias J, Kondamudi NP. Alagille Syndrome. [Updated 2023 Aug 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.
2. Cleveland Clinic, What Is Alagille Syndrome? (2022). https://my.clevelandclinic.org/health/diseases/23540-alagille-syndrome?
3. Saleh M, Kamath B, Chitayat D. Alagille syndrome: clinical perspectives. Appl Clin Genet. 2016;9:75-82
https://doi.org/10.2147/TACG.S86420
4. Ayoub, Mohammed D., and Binita M. Kamath. 2020. "Alagille Syndrome: Diagnostic Challenges and Advances in Management" Diagnostics 10, no. 11: 907. https://doi.org/10.3390/diagnostics10110907
5. Mitchell E, Gilbert M, Loomes KM. Alagille Syndrome. Clin Liver Dis. 2018 Nov;22(4):625-641. doi: 10.1016/j.cld.2018.06.001. Epub 2018 Aug 22. PMID: 30266153.
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