Antenatal diagnosis of Congenital Anomalies of Kidneys and Urinary Tract (CAKUT)
Genetics in Congenital Disorders of the Urinary Tract
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Genetics in Congenital Disorders of the Urinary Tract 26 th International Congress of Pediatrics, Tehran, Iran M. Rafati MD PhD Assistant Professor of Medical Genetics Avicenna Research Institute 1 10/18/2014
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Transcript of 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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High Incidence Rate
Represent 35% to 45% of all congenital abnormalities
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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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