Trip Answers

Question answered:28/05/08

We searched Medline and TRIP databases and found a number of articles suggesting genetic factors associated with unilateral renal agenesis (URA), which may sometimes occur as part of a multi-organ syndrome, although teratogenic causation has also been associated with URA.  The following, which cites a recommendation for screening of siblings, is taken from the most recent review article we found on URA [1].

 

“ASSOCIATED ANOMALIES, AND GENETIC AND TERATOGENIC CAUSATION
Anomalies outside the renal tract can be associated with URA, including absence of a uterine horn or vas deferens ipsilateral to the absent kidney, respectively, emphasizing close relationships between paramesonephric and mesonephric duct development and nephrogenesis itself. Dursun et al., detected non-urological anomalies in 44% of 87 consecutive cases of congenital SFK, with cardiac and gastrointestinal malformations being especially common. Sometimes RA occurs as part of a multi-organ syndrome (Table 1), and several of these have defined genetic bases. Not unexpectedly, the normal versions of genes mutated in such individuals are expressed during differentiation of normal kidneys and ureters. Gene mutations in branchio-oto-renal, Townes Brockes and the renal cysts and diabetes syndromes encode
transcription factor and related proteins that modulate expression of other genes; in Fraser and X-linked Kallmann syndromes, the relevant proteins are on surfaces of renal epithelia, and probably mediate cell–cell and cell–matrix interactions; in Rokitansky-Kuster-Hauser syndrome, there is a report of mutation of a locally acting growth factor.  Even in the absence of non-renal tract features, RA can be familial, sometimes apparently inherited as a dominant trait with incomplete penetrance. The risk to close relatives might be greater when the index case has bilateral RA, and Roodhooft et al. recommend ‘ultrasonographic screening for parents and siblings of infants born with agenesis or dysgenesis of both kidneys or with agenesis of one kidney and dysgenesis of the other, since renal malformations may have medical implications even for asymptomatic patients’.

 

Finally, regarding teratogenic causation, poorly controlled maternal diabetes mellitus and use of specific drugs during pregnancy (e.g. those which inhibit the reninangiotensin system) have been associated with RA in progeny. Other agents, such as high doses of vitamin A derivates, can cause RA in experimental animals.”

 

Table 1 referred to above is as follows:

 

TABLE 1
Multi-organ syndromes associated with RA
Syndrome
Branchio-oto–renal syndrome: EYA1(Eyes Absent 1) dominant mutation; hearing loss, pre-auricular pits, branchial clefts.
DiGeorge syndrome:deletion of 22q11: congenital heart disease, hypocalcaemia, immunodeficiency,and neurocognitive disorders.
Fanconi anaemia: caused by recessive mutation of several genes; pancytopenia.
Fraser syndrome:FRAS1 autosomal recessive mutations; cryptophthalmos, cutaneous syndactyly, malformations of the larynx and ambiguous genitalia.
Kallmann syndrome:Anosmin-1 X-linked recessive mutation: hypogonadotrophic hypogonadism and anosmia.
Klinefelter syndrome:47,XXY: small, firm testis, gynaecomastia, azoospermia and hypergonadotrophic hypogonadism.
Rokitansky-Kuster–Hauser syndrome:WNT4(wingless-type MMTV integration site family member 4) dominant mutation; absent/rudimentary upper vagina and uterus.
MURCS association: genetic basis undefined; Müllerian duct aplasia-hypoplasia (MU), renal malformations (R) and cervicothoracic somite dysplasia (CS).
Poland syndrome: genetic basis undefined; unilateral hypoplasia of pectoralis major muscle and ipsilateral syndactyly.
Renal cysts and diabetes syndrome:HNF1?(hepatocyte nuclear factor?) dominant mutations; diabetes mellitus, hyperuricaemia and uterine malformations.
Townes–Brocks syndrome:SALL1(sal-like 1/homologue of Drosophila spalt) dominant mutation: imperforate anus, triphalangeal/bifid thumb, rocker bottom feet, sensorineural hearing loss, hypospadias.
Williams–Beuren syndrome; deletion of 7q11.23; developmental delay, cardiovascular anomalies, mental retardation and facial dysmorphology.

 

The full text of this article is available via the link below.

 

Reference

1. Woolf AS and Hillman KA.  Unilateral renal agenesis and the congenital solitary functioning kidney: developmental, genetic and clinical perspectives. BJU International Sept 2006 (epub).
(http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1464-410X.2006.06504.x)

 

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