Identification of a pathogenic variant in KAT6B in a patient with genitopatellar syndrome: A case report

We present the case of a two-year-old female patient, the only child of a non-consanguineous Latin American couple. The child was referred for genetic investigation due to multiple congenital malformations and neurological impairment. Her clinical history revealed low weight for age, agenesis of the corpus callosum, cleft palate, retrognathia, ambiguous genitalia. She showed epileptic seizures, limb hypotonia, bilateral hydronephrosis associated with ureteral stenosis, need for bilateral nephrostomy, stage 1 chronic kidney disease, as well as dysphagia, and recurrent hematochezia. This constellation of findings initially raised the suspicion of a malformation syndrome of genetic origin. Chromosomal microarray analysis (CMA), as well as conventional karyotyping, did not reveal any significant abnormalities. However, whole exome sequencing (WES) identified a pathogenic heterozygous variant in the KAT6B gene, associated with Genitopatellar Syndrome (OMIM #606170). The variant was confirmed by Sanger sequencing, and parental segregation analysis demonstrated that it was a de novo event. The molecular finding is consistent with the clinical presentation, since Genitopatellar Syndrome is mainly characterized by neurological, craniofacial, renal, and genital anomalies. Although the patient did not present with absence or anomalies of the patellae, a frequent finding in this syndrome, the presence of the other clinical manifestations, together with pathogenic variant validation, supported the establishment of a definitive diagnosis.