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

We report the case of a 13-month-old female with multiple congenital anomalies including microcephaly, generalized hypotonia, sensorineural hearing loss, visual impairment, alopecia, and hypoplastic kidneys with chronic kidney disease, and dysmorphic craniofacial features. Extensive metabolic and immunodeficiency workups were unremarkable. Genetic evaluation was conducted in a stepwise approach, and with exome sequencing (ES), we identified two compound heterozygous variants of uncertain significance in the ZPR1 gene. These variants resembled previously reported pathogenic ZPR1 variants associated with a syndrome characterized by growth restriction, craniofacial abnormalities, alopecia, and hypoplastic kidneys. With variant interpretations and clinical comparisons to our patient, we strongly suspect a likely pathogenic role for the ZPR1 variants in this patient's multisystem phenotype, highlighting the importance of exome sequencing in diagnosing medically complex pediatric patients.