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Early-Onset Pectus Excavatum Is More Likely to Be Part of a Genetic Variation
Ryan Billar1, Stijn Heyman2, Sarina Kant3
1Department of Pediatric Surgery, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands.
Insights
Early-onset pectus excavatum (PE) is frequently linked to genetic variations. This suggests that genetic counseling should be considered for children diagnosed with early-onset PE.
Area of Science:
- Medical Genetics
- Pediatric Surgery
Background:
- Pectus excavatum (PE) is a chest wall deformity.
- Genetic variations underlying PE are considered rare.
- Congenital PE cases are typically identified within the first decade of life.
Purpose of the Study:
- To investigate the association between early-onset PE and genetic variations.
- To compare the likelihood of genetic involvement in early-onset PE versus PE presenting later in life.
Main Methods:
- Retrospective analysis of young PE patients (<11 years) referred for genetic counseling.
- Screening by two clinical geneticists.
- Molecular analysis based on differential diagnosis.
Main Results:
- Pathogenic genetic variations were identified in 44% (8/18) of participants.
- Identified variations included syndromic disorders (e.g., Noonan syndrome), chromosomal abnormalities, connective tissue disease (Loeys-Dietz syndrome), and neuromuscular disorders (BICD2 gene).
Conclusions:
- Early-onset PE is more strongly associated with genetic variations compared to PE that manifests during puberty or adolescence.
- Genetic counseling referral is recommended for pediatric patients with early-onset PE.
Background:
Potential underlying genetic variations of pectus excavatum (PE) are quite rare. Only one-fifth of PE cases are identified in the first decade of life and thus are of congenital origin. The objective of this study is to test if early-onset PE is more likely to be part of genetic variations than PE that becomes apparent during puberty or adolescence.
Materials And Methods:
Children younger than 11 years who presented with PE to the outpatient clinic of the Department of Pediatric Surgery at our center between 2014 and 2020 were screened by two clinical geneticists separately. Molecular analysis was performed based on the differential diagnosis. Data of all young PE patients who already had been referred for genetic counseling were analyzed retrospectively.
Results:
Pathogenic genetic variations were found in 8 of the 18 participants (44%): 3 syndromic disorders (Catel-Manzke syndrome and two Noonan syndromes), 3 chromosomal disorders (16p13.11 microduplication syndrome, 22q11.21 microduplication syndrome, and genetic gain at 1q44), 1 connective tissue disease (Loeys-Dietz syndrome), and 1 neuromuscular disorder (pathogenic variation in BICD2 gene).
Conclusion:
Early-onset PE is more likely to be part of genetic variations than PE that becomes apparent during puberty or adolescence. Referral for genetic counseling should therefore be considered.
Trial Registration:
NCT05443113.
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