Genitopatellar Syndrome Secondary to De Novo KAT6B Mutation: The First Genetically Confirmed Case in South Korea

Abstract

Genitopatellar syndrome (GPS) is a rare disorder characterized by patellar hypoplasia, flexion contractures of the lower limbs, psychomotor retardation and genital and renal anomalies. We report the case of a female infant diagnosed with GPS to a KAT6B gene mutation, which was identified using whole exome sequencing.

Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants

“…13,[24][25][26][27][28] Affected individuals, including the ones in this report, often present with other cerebral/neurological anomalies such as colpocephaly, hydrocephaly, dilated ventricles, or ventriculomegaly (11 individuals); pachygyria or simplification of cortical sulci (4 individuals); delayed white matter myelination or hypomyelination (4 individuals); and gray matter heterotopia (3 individuals). 6,17,26,27,[29][30][31][32] Each of the following anomalies were described in two individuals: periventricular gliosis, agenesis of the septum pellucidum, telencephalic or periventricular leukoencephalopathy, and hypertonia/dystonia; other anomalies were reported in only one individual each: cortical atrophy, agenesis of the anterior commissure, cerebral palsy, lenticulostriate vasculopathy, brainstem hypoplasia, unspecified cerebellar abnormalities, spina bifida, Horner syndrome, nonspecific gray matter differences, partial agenesis of the cingulate gyrus, and wide Virchow-Robin spaces. 24,26,30,31,33 A newborn from this cohort presented with lissencephaly, cerebellar/cerebral hemorrhage, and hypoplasia/immaturity of the cerebellar cortex.…”

“…19,25,26,[30][31][32]34 Telecanthus, epicanthus inversus, and hypertelorism are also sometimes noted. 17,24,25,[27][28][29]32,36,37 Craniofacial features…”

“…Renal anomalies are more commonly observed in GPS, with hydronephrosis and multicystic kidneys being most common. 6,7,13,26,27,30,36 Kim et al reported a girl with GPS who had multicystic dysplastic kidneys leading to renal failure and pulmonary hypoplasia/hypertension. 27 In this cohort, two newborns with GPS also presented with an oligohydramnios sequence due to bilateral renal hypoplasia or dysplasia.…”

“…6,7,13,26,27,30,36 Kim et al reported a girl with GPS who had multicystic dysplastic kidneys leading to renal failure and pulmonary hypoplasia/hypertension. 27 In this cohort, two newborns with GPS also presented with an oligohydramnios sequence due to bilateral renal hypoplasia or dysplasia. In addition, one individual had stage III bilateral vesicoureteral reflux with renal hypoplasia, one had unilateral ureteropelvic junction obstruction, and another had lower urinary tract obstruction with reflux and dysplastic cystic kidneys.…”

A neonate with Say–Barber–Biesecker–Young–Simpson syndrome with a novel pathogenic mutation in KAT6B gene: A case report

“…Kim et al [16] reported the familial inherited mutation of the KAT6B variant (c.2292C>T, p.His767Tyr) causing relatively mild disease in three individuals with SBBYSS. In Korea, two cases have reported KAT6B mutation including GPS (NM_012330.3: c4543C>T, p.Gln1515Ter) and familial SBBYSS mentioned above [16,17].…”