Fetal megacystis

Fetal megacystis occurs in the antenatal period in around 1 in 1,500 pregnancies. It is much more commonly seen in male fetuses than in female fetuses.

Diagnosis

• In the first trimester, fetal megacystis is defined as a longitudinal bladder diameter greater than 7mm.
• In the second and third trimesters, it is defined as an enlarged bladder failing to empty during an extended ultrasound examination lasting at least 40 minutes.
• The main cause of fetal megacystis is bladder outlet obstruction, also known as lower urinary tract obstruction.

Prognosis

• If the bladder diameter is 7mm to 15mm at the first trimester scan, resolution occurs in around 90% of cases.
• If the bladder diameter is greater than 15mm, it is likely to be associated with a poor prognosis: usually hydronephrosis is progressive and results in dysplastic, non-functioning kidneys.
• Additionally, where the bladder obstruction is significant, there may be oligohydramnios and resultant pulmonary hypoplasia (poor lung development), which is associated with perinatal death.

For an example of bladder obstruction, take a look at the ultrasound video on this Fetal Medicine Foundation webpage.

Megacystis diagnosed during a first trimester ultrasound can be associated with aneuploidy, usually trisomy 18 (Edward syndrome), trisomy 13 (Patau syndrome) or rarer genetic syndromes.

The chance of an underlying genetic diagnosis varies depending on the extent of obstruction and bladder dilatation. There is:

• a 25% chance where the measurement is 7mm to 15mm; and
• a 10% chance where the measurement is greater than 15mm.

The presence of other congenital anomalies or markers of aneuploidy increases the change of an underlying genetic diagnosis.

Diagnosis of the underlying cause of fetal megacystis can help inform pregnancy decision-making and management.

Consideration must be given to both genetic and non-genetic causes. Genetic causes can be split into chromosomal causes, including aneuploidy, and single gene causes, including the autosomal recessive condition megacystis-microcolon-intestinal hypoperistalsis syndrome. Mechanical obstruction, including posterior urethral valves in male fetuses, is the most common non-genetic cause.

In isolated cases, parents should be offered common aneuploidy testing. For further information, please see Fetus with an isolated congenital anomaly.

When additional congenital anomalies are present, the family may be eligible for fetal exome sequencing via the National Genomic Test Directory test code R21 Rapid prenatal exome sequencing, in addition to aneuploidy testing.

Megacystis is not thought to be an inherited condition in itself. If an underlying genetic cause is found, the recurrence risk will depend on the specific diagnosis.

If a trisomy (such as Down syndrome, Edwards syndrome or Patau syndrome) is identified, the recurrence risk is likely to be low, as most cases of trisomy are caused by nondisjunction (an error in cell division in which chromosomes fail to separate properly during the creation of the egg or sperm). However, trisomies can also arise from balanced structural chromosomal rearrangements in parents – for example, reciprocal chromosome translocations or Robertsonian chromosome translocations. In such cases, the recurrence risk can be substantially higher, and additional reproductive options are often available; in these cases, patients should be referred for tailored genetic counselling. Genomic laboratories can advise clinicians regarding the need for parental testing for underlying structural rearrangements.

When trisomy arises from nondisjunction, the recurrence risk is slightly raised compared to the baseline, and non-invasive testing is available. For more information, please see Pregnant woman with a previous pregnancy or baby diagnosed with full trisomy 21, 18 or 13.

If a single gene condition is identified through fetal exome sequencing, recurrence risks will depend on the inheritance mechanism and the outcome of parental genomic testing. For example, megacystis-microcolon-intestinal hypoperistalsis syndrome can be autosomal recessive or autosomal dominant, depending on the specific genetic cause. For autosomal recessive cases, parents are typically asymptomatic carriers, which confers a 25% recurrence risk for subsequent pregnancies. Genetic counselling that covers reproductive options is advised.

Typically, obstructive causes of fetal megacystis do not have a genetic basis and are associated with a low risk of recurrence.

If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

Management of fetal megacystis depends on the cause, and patients are typically referred to fetal medicine services for ongoing care. Serial ultrasound scans are recommended to monitor the megacystis and look for any associated malformations or markers.

The prognosis of megacystis varies widely depending on the severity, cause and associated complications. In the most severe cases, it can cause pulmonary hypoplasia and irreversible renal dysplasia; however, many cases are transient and self limiting.

Postnatally, affected children are often more susceptible to kidney infections and kidney failure. Some may eventually require renal replacement therapy, including transplantation. Individuals who were affected by antenatal megacystis may also experience long-term bladder symptoms and/or bladder dysfunction, as well as poor growth and musculoskeletal problems.

Long-term follow-up is overseen by a paediatric urologist and nephrologist.

For clinicians

• NHS England: National Genomic Test Directory
• The Fetal Medicine Foundation: Urethral obstruction

References:

• Lesieur E, Barrois M, Bourdon M and others. ‘Megacystis in the first trimester of pregnancy: Prognostic factors and perinatal outcomes‘. PLOS One 2021: volume 16, issue 9. DOI: 1371/journal.pone.0255890

For patients

• Antenatal Results & Choices
• International Society of Ultrasound in Obstetrics and Gynaecology (ISUOG): Fetal megacystis