ESPN 54th Annual Meeting

ESPN 2022


 
Novel Renal Phenotypes in KBG syndrome: A case series
NATALIE WYATT 1 FAIDRA VELIGRATLI 1 AOIFE WATERS 1

1- GREAT ORMOND STREET HOSPITAL
 
Introduction:

KBG syndrome is a rare autosomal dominant syndrome associated with mutations or deletions in ANKRD11. Named for the three families first identified, features of KBG syndrome include macrodontia of upper central incisors, distinctive facies, skeletal abnormalities, seizures, and developmental delay. To date renal manifestations have not been described in the literature. ANKRD11 gene encodes for ankyrin repeat domain-containing protein which inhibits ligand-dependent activation of transcription. It is expressed in the kidney. We present two cases which, for the first time, describe kidney anomalies in children with KBG syndrome.

Material and methods:

We retrospectively reviewed paediatric cases of KBG syndrome associated with renal anomalies presenting to Great Ormond Street Hospital in 2021. Genetic diagnosis was made with the GOSHome gene panel test (DDTOP).

Results:

Two cases have been identified. A 4-year-old female presenting with seizures, developmental delay, and bilateral conductive hearing loss. Genetic testing identified a heterozygous frameshift mutation in ANKRD11 c.1356_1359del p.(Asn452Lysfs*2). Ultrasound revealed a left kidney duplex malformation and a normal right kidney in the context of normal kidney function, blood pressure and negative urine dipstick test. A second unrelated, female with developmental delay and abnormal feet posturing with a heterozygous mutation in ANKRD11 c.6538dup, p.(SER2180fs) was incidentally found to have chronic kidney disease (eGFR is 45ml/min/1.73m2) during investigation of suboptimal growth. Ultrasound revealed bilateral pelvicalyceal and ureteric dilatation, loss of corticomedullary differentiation but appropriately grown kidneys. The long-term prognosis is unknown and thus both are undergoing follow up. 

Conclusions:

To date more than 200 cases of KBG syndrome have been reported in the literature. This is the first description of an association with kidney anomalies. Imaging and assessment of kidney function should be performed in those diagnosed with KBG syndrome. Furthermore, these cases highlight the importance of investigating the genetic basis of CAKUT in the context of extra-renal manifestations.