Nephrology Dialysis Transplantation, Vol 12, Issue 11 2284-2288, Copyright © 1997 by Oxford University Press
M Griffin, V Gamble, D Milliner, M Gomez, P Harris and E Torres
Background: Childhood presentation of polycystic
kidney disease has been reported with tuberous sclerosis complex (TSC).
Recently some such cases have been shown to be due to combined deletion of
the PKD1 and TSC2 genes, which
lie close together on chromosome 16. The phenomenon of anticipation,
whereby disease presentation occurs at a progressively earlier age in each
generation, has been suggested to occur in autosomal dominant polycystic
kidney disease (ADPKD). We have carried out a genetic study of a family in
which these issues became clinically relevant. Neonatal presentation of
polycystic kidneys occurred in an individual with a maternal family history
of epilepsy and features of TSC without renal cystic disease.
Method: Detailed historical and clinical profiles were
gathered for three generations of the maternal and paternal families. Both
parents underwent renal ultrasound scanning. Genomic DNA was obtained from
affected and unaffected individuals from the maternal family and used for
linkage analysis to gene loci for TSC. Results: Renal
cysts were not present in the mother by ultrasound. Linkage to
TSC2 was found for members of the maternal family with
clinical features of TSC. While a diagnosis of TSC was confirmed in her
mother the child was found not to have inherited the disease-related
allele. The father was found to have asymptomatic bilateral polycystic
kidneys consistent with ADPKD. The presence of ADPKD in other paternal
relatives could not be confirmed. Conclusions: The
index case was found to have paternally inherited ADPKD with unusually
early presentation. While at risk for concomitant maternal inheritance of
TSC this diagnosis was ruled out by linkage analysis studies. The ability
to clarify the true nature of a complex inherited condition greatly
facilitates future management and counselling. The mechanisms underlying
phenotypic heterogeneity in ADPKD remain to be clearly defined and are the
subject of ongoing investigation. Key words:
hereditary disease; linkage analysis; PKD1, polycystic kidney disease;
tuberous sclerosis; TSC2
ORIGINAL ARTICLES
Neonatal presentation of autosomal dominant polycystic kidney disease with a maternal history of tuberous sclerosis
Department of Internal Medicine, Division of Nephrology and Internal Medicine, Mayo Clinic, 200 Second St., SW, Rochester, MN 55905, USA; Department of Paediatric Neurology, Mayo Clinic and Mayo Foundation, Rochester, MN, USA; MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK; Corresponding author
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