Kidney agenesis / dysgenesis

Kidney agenesis and dysgenesis form a contiguous developmental spectrum encompassing unilateral and bilateral renal agenesis, renal hypoplasia and dysplasia, and multicystic dysplastic kidney, and represent a core subset of . Onset is prenatal: most cases are detected on antenatal ultrasound or at birth. Unilateral renal agenesis is more prevalent and may lead to long-term renal complications, whereas bilateral renal agenesis is typically lethal in the neonatal period. Both nonsyndromic (isolated) and syndromic presentations are clinically relevant; in syndromic forms, renal hypodysplasia or agenesis occurs alongside extrarenal features such as ocular, branchio-otic, pancreatic, cardiac, palatal, or neurodevelopmental anomalies. CAKUT collectively accounts for a substantial proportion of paediatric chronic kidney disease and of children requiring kidney replacement therapy.

The estimated overall prevalence of renal agenesis is 2.28 per 10,000 births (unilateral 1.94 per 10,000; bilateral 0.30 per 10,000), as reported in a large-scale Chinese national surveillance cohort of approximately 25.9 million births. This aligns closely with European epidemiological data curated by Orphanet and the European Reference Networks (ERKNet), where the birth prevalence of unilateral renal agenesis is estimated at approximately 1 in 2,000 births (~5 per 10,000) and the foetal prevalence of bilateral renal agenesis is estimated at 1 in 8,500 births (~1.18 per 10,000). The proportion of cases directly attributable to monogenic and genetic forms across the full spectrum remains unquantified.

A large number of genes have been associated with kidney agenesis and dysgenesis, and submicroscopic microdeletions and microduplications represent a further mechanistic class. The genetic forms can be grouped into isolated (nonsyndromic) CAKUT and syndromic or chromosomal/genomic CAKUT. HNF1B (sequence variants and the recurrent 17q12 microdeletion) is the most frequently detected single-gene cause. Other examples include renal coloboma syndrome (PAX2) among isolated forms and 22q11.2 deletion syndrome (CRKL) among syndromic forms.

The genetic conditions associated with kidney agenesis and dysgenesis follow heterogeneous inheritance patterns. Across the spectrum, autosomal dominant transmission predominates among identified monogenic causes; autosomal recessive, X-linked, and multifactorial contributions are also documented, with both monogenic variants and complex inheritance recognised.

• Where kidney agenesis or dysgenesis is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

• Hilger AC, Westland R, Hoefele J. Genetics of CAKUT. Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V. 2026;38(1):3-10. doi: 10.1515/medgen-2025-2053. PMID: . PMCID: PMC12910339.
• Gao Y, Xu W, Li W, Chen Z, Li Q, Liu Z, et al. A surveillance-based epidemiological study of renal agenesis in 25 million births in china, 2007-2020. BMC pregnancy and childbirth. 2025;25(1):689. doi: 10.1186/s12884-025-07807-6. PMID: . PMCID: PMC12225177.
• Vendrig LM, Ten Hoor MAC, König BH, Lekkerkerker I, Renkema KY, Schreuder MF, et al. Translational strategies to uncover the etiology of congenital anomalies of the kidney and urinary tract. Pediatric nephrology (Berlin, Germany). 2025;40(3):685-699. doi: 10.1007/s00467-024-06479-2. PMID: . PMCID: PMC11753331.