genetics in congenital disorders of the urinary tract

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Genetics in Congenital Disorders of the Urinary Tract

26th International Congress of Pediatrics, Tehran, Iran M. Rafati MD PhD

Assistant Professor of Medical Genetics

Avicenna Research Institute

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Rafati M

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High Incidence Rate

Represent 35% to 45% of all congenital abnormalities

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Rafati M

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Congenital Urinary Tract Anomalies (UTA)

Include anomalies of: Kidneys Ureters Bladder Urethra

Classification: Errors of organogenesis Errors of migration and position Obstruction

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Prenatal Hydronephrosis

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Prenatal Hydronephrosis

Hydronephrosis is the most common abnormality detected on prenatal ultrasonography.

In the United States, 3 million maternal ultrasounds are performed annually with hydronephrosis being the most commonly detected anomaly (as many as 42,000 fetuses, 1.4%)

It accounts for about 50% of all prenatally detected defects. 

up to one half of these neonates do not have hydronephrosis on the postnatal ultrasound.

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Prenatal Hydronephrosis

Etiology: Physiologic or benign dilation Ureteropelvic junction (UPJ) obstruction (64%) The remaining 36% are secondary to:

Vesicoureteral reflux Megaureter Posterior urethral valves

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Contribution of Genetics

Isolated or Associated with

Other Anomalies?

Unilateral or Bilateral?Severity?

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Association with other anomalies UTA are frequently associated (72%) with other structural

anomalies Structural anomalies of most organ systems have an

increased risk for association with UTA

%with renal anomalies

Structural anomaly

42 Absent gallbladder25 Anencephaly80 Caudal dysplasia10 Heart defects20 Anorectal malformations4 Gastroschisis100 Sirenomelia VATER

association

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Genetics in hydronephrosis

Multifactorial disorder Low recurrence risk

Chromosome abnormalities Risk of fetal chromosome abnormality

Isolated hydronephrosis: 3 times Hydronephrosis associated with other anomalies: 30 times

risk Autosomal dominant inheritance

Few reported families

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Chromosomal Aneuploidies among Fetuses with Hydronephrosis

Bilateral Unilateral Renal Anomaly

Other Anomalies

Isolated Other Anomalies

Isolated

32%) 30/95( 3%) 5/163( 25%) 2/8( 0%) 0/10( Mild Hydronephrosis

26%) 10/38( 6%) 5/81( - - Moderate Hydronephrosis

- - 44%) 7/11( 1%) 1/76( Severe Hydronephrosis

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Importance of Diagnosis

Pathology and genetic investigation of products of conception

Diagnosis

Genetic Investigation

Prevention in Future Pregnancies

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Diagnostic approach

Chromosome study Karyotype Array-based techniques

Monogenic disorders Targeted molecular genetic study Genomic studies (next-generation sequencing

technique)

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Chromosome study

Normal karyotype does not rule out chromosome abnormalities

Array-based techniques Different resolution

CGH array Oligoarray SNP array

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Next generation sequencing techniques

High throughput Molecular investigation of a wide range of genetic

disorders in a single experiment Whole exome sequencing

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Thanks for Your Attention

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