Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports

Area of Science:

• Genetics
• Pediatrics
• Cardiology

Background:

• CHARGE syndrome and 22q11.2 deletion syndrome (DiGeorge anomaly) are associated with significant cardiovascular malformations.
• Specific heart defects like interrupted aortic arch type B are linked to 22q11.2 deletion syndrome, while CHARGE syndrome shows overrepresentation of conotruncal and atrioventricular septal defects.
• CHD7 gene mutations are found in ~66% of CHARGE syndrome cases, and 22q11.2 microdeletions are present in >95% of 22q11.2 deletion syndrome cases.

Purpose of the Study:

• To report two cases with overlapping dysmorphic features of both CHARGE syndrome and 22q11.2 deletion syndrome.
• To highlight the diagnostic challenge when cardiovascular malformations typical of 22q11.2 deletion syndrome are present without the deletion.
• To emphasize the importance of investigating CHARGE syndrome in such cases.

Main Methods:

• Clinical case reporting of two patients.
• Review of dysmorphic features, cardiovascular malformations, and genetic testing (CHD7 mutation, 22q11.2 deletion).

Main Results:

• Two patients presented with features of both syndromes, including interrupted aortic arch type B, but lacked 22q11.2 deletion.
• Both patients exhibited characteristic CHARGE syndrome features: ear and genital malformations, limb abnormalities, and endocrinopathies.
• CHD7 gene mutation was confirmed in one patient.

Conclusions:

• When cardiovascular malformations typically associated with 22q11.2 deletion syndrome are observed without the deletion, CHARGE syndrome should be considered.
• This suggests a potential overlap or diagnostic confusion between these syndromes, necessitating a thorough evaluation for CHARGE syndrome features.