Related Experiment Videos
A pedigree study of perinatally lethal renal disease
Insights
Perinatally lethal renal disease (PLRD) studies reveal genetic links between bilateral renal agenesis (BRA) and unilateral renal agenesis/renal dysplasia (URA/RD). Recurrence risks for PLRD vary, with higher risks for BRA and urogenital defects alone.
Area of Science:
- Medical Genetics
- Developmental Biology
- Pediatric Nephrology
Background:
- Perinatally lethal renal disease (PLRD) encompasses conditions like bilateral renal agenesis (BRA), unilateral agenesis with renal dysplasia (URA/RD), and bilateral renal dysplasia (BRD).
- Understanding the genetic basis and recurrence risks of PLRD is crucial for effective genetic counseling.
Purpose of the Study:
- To investigate the familial occurrence and recurrence risks of perinatally lethal renal disease (PLRD) in Victoria, Australia.
- To determine the genetic relationship between different forms of PLRD, specifically BRA and URA/RD.
Main Methods:
- A family study was conducted using hospital and necropsy records from 1961 to 1980, identifying 221 cases of PLRD.
- Parental interviews and renal ultrasound examinations were performed on 153 parents from 82 families.
- Recurrence risks were calculated based on affected siblings and first cousins in families with PLRD.
Main Results:
- Bilateral renal agenesis (BRA) was the most common form (134 cases), followed by bilateral renal dysplasia (BRD) (42 cases) and unilateral agenesis with renal dysplasia (URA/RD) (34 cases).
- For families with PLRD, 3.6% of siblings and 0.2% of first cousins were affected.
- When the index case had BRA with urogenital defects, the sibling recurrence risk was 8%; for BRA as part of a multiple malformation complex, the recurrence risk of multiple malformations was 12.5%.
Conclusions:
- Bilateral renal agenesis (BRA) and unilateral renal agenesis/renal dysplasia (URA/RD) are genetically related conditions.
- Genetic counseling should consider the specific presentation of PLRD; recurrence risk is higher for BRA with isolated urogenital defects (8%) compared to BRA within a malformation complex (low BRA recurrence, but 12.5% for malformations).
- Renal ultrasound findings in parents were not informative for predicting recurrence.
Abstract:
A family study of perinatally lethal renal disease (PLRD) was undertaken in the State of Victoria, Australia, for the years 1961 to 1980. A total of 221 cases was ascertained through hospital and necropsy records and confirmed by necropsy findings. There were 134 cases of bilateral renal agenesis (BRA), 34 cases of unilateral agenesis with dysplasia of the other kidney (URA/RD), 42 cases of bilateral renal dysplasia (BRD), and 11 cases of renal aplasia. Parents of 131 babies were interviewed and 153 parents from 82 families had a renal ultrasound examination. In the period of best ascertainment (1975 to 1980) the frequency of PLRD was 0.27 per 1000 and of BRA 0.16 per 1000. There were 10 cases of sirenomelia, a frequency of 0.008 per 1000. For all families of PLRD, 15 of 423 (3.6%) sibs and three of 1579 (0.2%) first cousins were affected. One family had three sibs with BRA and four had two sibs with BRA. One pair of sibs and two first cousins had BRA in one and URA/RD in the other affected. One baby had BRD with an affected first cousin. The nature of the renal lesion was not established. When the index case had BRA, 14 in 283 (5.6%) sibs had PLRD. Where the index case had BRA and urogenital defects, but no birth defects in other organs, 12 of 148 sibs (8%) were affected. None of the sibs had BRA when the index case had BRA as part of a multiple malformation complex. In the multiple malformation group, however, five of 40 (12.5%) sibs had similar patterns of malformations. Renal ultrasound abnormalities were no more frequent in parents of two affected babies (one of 18) than in the other parents (nine of 135). Our findings confirm that BRA and URA are genetically related. There are a number of conclusions which are important for genetic counselling. There is a high likelihood of recurrence (8%) in sibs when the index case has BRA and urogenital abnormalities alone. When BRA is part of a multiple malformation complex, the risk of recurrence of multiple malformations is significant (12.5%), but risk recurrence of BRA is low. The finding of renal ultrasound abnormalities in the parents was not informative.