Unique phenotype in a patient with CHARGE syndrome

Area of Science:

• Genetics
• Pediatrics
• Endocrinology

Background:

• CHARGE syndrome is a complex, heterogeneous disorder with a known genetic basis in CHD7.
• Classic features include Coloboma, Heart defects, Atresia choanae, Retarded growth and development, Genitourinary abnormalities, and Ear anomalies/deafness.
• Phenotypic overlap with other genetic syndromes is increasingly recognized.

Purpose of the Study:

• To report a patient with an atypical presentation of CHARGE syndrome.
• To characterize a novel CHD7 mutation.
• To broaden the understanding of CHARGE syndrome's phenotypic spectrum.

Main Methods:

• Clinical case presentation and genetic analysis.
• Structural modeling of the CHD7 protein.
• Murine expression studies.

Main Results:

• The patient presented with primary hypoparathyroidism, a limb anomaly, and bilateral multicystic dysplastic kidneys, features not previously reported together in CHARGE syndrome.
• A putative CHD7 G744S missense mutation was identified and characterized.
• The findings expand the known phenotypic variability of CHARGE syndrome.

Conclusions:

• The CHARGE syndrome phenotype is more diverse than traditionally defined.
• Genetic testing for CHARGE syndrome should be considered even in the absence of all classic features.
• This case highlights the importance of comprehensive evaluation and genetic analysis in complex pediatric cases.