Chest wall deformities and their possible associations with different genetic syndromes

Our primary objective was to identify discrete and syndromic cases of Pectus excavatum (PE) and Pectus carinatum (PC). We also intended to highlight the significance of further genetic exploration in clinically suspected syndromic cases of PC and PE. Pectus excavatum (PE) and Pectus carinatum (PC) are the most common morphological chest wall deformities. Although various hypotheses have been put forth, the pathogenesis of both entities is largely unknown. Clinicians often refer such cases for further genetic evaluation to exclude an associated underlying connective tissue disorder or a syndrome. Additionally, a detailed anamnesis with focused family history and thorough dysmorphological physical examination was done. PE and PC are considered isolated abnormalities if there is the absence of features of other syndromes, eliminating the need for further genetic evaluations. It is believed that the pattern of inheritance of these non-syndromic isolated PE and PC cases with positive family history could be multifactorial in nature. The recurrence risk of such isolated cases is thought to be low. Further diagnostic studies are indicated as PE and PC could be a part of a syndrome. Among the many syndromes, the most common monogenic syndromes associated with PE and PC are Marfan's and Noonan's.

After obtaining the consent, we compiled a database of the patients who presented with chest wall deformities during the period 2017-2019. We selected 70 cases with PC and PE deformities to identify the discrete and syndromic PC and PE cases. During the study, we perused the cytogenetic and/or molecular analyses, that had been conducted to confirm the clinically suspected syndromic cases. We also scrutinized for the presence of PC and PE cases that are associated with the rare syndrome (s).

Various genetic abnormalities were identified in 28 (40%) of the 70 cases that had been diagnosed with chest wall abnormalities. Along with PE and PC, other thoracic wall abnormalities were also identified, such as the broad chest, bell-shaped thorax, and elongated or enlarged thorax. One case of a rare genetic disorder of Morquio syndrome associated with PC was also identified. Novel (previously unpublished) genomic variants are reported here.

It is important to delve deeper when encountering cases of PE and PC by conducting a further genetic exploration of such cases to identify syndromic associations that cause other structural and functional disorders, diagnosis of which might be missed during the early developmental period. Early identification of such disorders may help us correcting the defects, slowing the progression of disease processes, and preparing better to deal with the potential outcome.