Lower urinary tract obstruction (LUTO)

LUTO presents prenatally as foetal megacystis with bilateral hydroureteronephrosis and variable oligohydramnios. On ultrasound, the bladder appears distended and thick-walled, and the ‘keyhole’ sign at the bladder neck is almost pathognomonic for posterior urethral valves. The condition is markedly more common in males, in whom isolated urethral anomalies account for the majority of cases, while non-obstructive megacystis (, , or cloacal malformations) underlies a smaller, often syndromic, fraction. Most foetuses come to attention on antenatal ultrasound before 20 weeks’ gestation, with severity ranging from isolated bladder distension with preserved amniotic fluid to severe oligo- or anhydramnios and associated secondary pulmonary hypoplasia. Both non-syndromic presentations (e.g., isolated posterior urethral valves) and syndromic forms within multisystem disorders are recognised, and persistent obstruction is one of the most frequent causes of paediatric end-stage kidney disease.

The estimated prevalence is 2.2 to 3.3 per 10,000 births. Generally, around 10% to 20% of all LUTO pregnancies involve an identifiable genetic aetiology.

A large number of genes have been associated with LUTO. The genetic forms of LUTO can be grouped into anatomical urethral obstruction, functional smooth-muscle disorders, and chromosomal or syndromic associations. The most common genetic cause is posterior urethral valves (predominant LUTO aetiology in males). Functional forms include (ACTG2-related smooth-muscle hypoperistalsis disorder). Chromosomal contributors include trisomy 18.

The genetic conditions associated with LUTO follow heterogeneous inheritance patterns. Reported modes include sporadic occurrence, autosomal dominant transmission (e.g., megacystis-microcolon-intestinal hypoperistalsis syndrome due to ACTG2), autosomal recessive transmission (e.g., the same syndrome due to LMOD1, MYH11, MYL9, or MYLK), and chromosomal aneuploidy. However, a significant proportion of cases remain genetically unexplained, which supports the assumption that the vast majority of isolated LUTO cases are multifactorial rather than monogenic in origin.

• Where LUTO 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.

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