Understanding the Role of Genetic Testing in Diagnosing a Complex Pediatric Case

Area of Science:

• Genetics
• Pediatrics
• Rare Diseases

Background:

• A 13-month-old female presented with multiple congenital anomalies including microcephaly, hypotonia, sensorineural hearing loss, visual impairment, alopecia, and hypoplastic kidneys with chronic kidney disease.
• Standard metabolic and immunodeficiency workups were inconclusive.

Purpose of the Study:

• To identify the genetic cause of the patient's complex multisystem phenotype.
• To evaluate the role of ZPR1 gene variants in pediatric congenital anomalies.

Main Methods:

• Comprehensive genetic evaluation using a stepwise approach.
• Whole exome sequencing (ES) was performed to identify causative genetic variants.
• Clinical data was compared with existing literature on ZPR1 gene variants.

Main Results:

• Exome sequencing identified two compound heterozygous variants of uncertain significance in the ZPR1 gene.
• These variants share similarities with previously reported pathogenic ZPR1 variants linked to a syndrome of growth restriction, craniofacial abnormalities, alopecia, and hypoplastic kidneys.
• The identified ZPR1 variants are strongly suspected to be pathogenic, explaining the patient's multisystem phenotype.

Conclusions:

• ZPR1 gene variants are implicated as a likely cause of the patient's complex congenital anomalies and chronic kidney disease.
• Exome sequencing is crucial for diagnosing rare and complex pediatric genetic disorders.
• This case expands the understanding of ZPR1-associated syndrome phenotypes.