title: Familial clustering of medullary sponge kidney is autosomal dominant with reduced penetrance and variable expressivity.
abstract: Medullary sponge kidney (MSK) is a renal malformation typically associated with nephrocalcinosis and recurrent calcium nephrolithiasis. Approximately 12% of recurrent stone formers have MSK, which is generally considered a sporadic disorder. Since its discovery, three pedigrees have been described in which an apparently autosomal dominant inheritance was suggested. Here, family members of 50 patients with MSK were systematically investigated by means of interviews, renal imaging, and biochemical studies in an effort to establish whether MSK is an inheritable disorder. Twenty-seven MSK probands had 59 first- and second-degree relatives of both genders with MSK in all generations. There were progressively lower mean levels of serum calcium, urinary sodium, pH, and volume, combined with higher serum phosphate and potassium from probands to relatives with bilateral, to those with unilateral, and to those unaffected by MSK. This suggests that most affected relatives have a milder form of MSK than the probands, which would explain why they had not been so diagnosed. Thus, our study provides strong evidence that familial clustering of MSK is common, and has an autosomal dominant inheritance, a reduced penetrance, and variable expressivity.
authors.affiliation: Division of Nephrology, Department of Biomedical and Surgical Sciences, University Hospital of Verona, Verona, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Fabris
authors.forename: Antonio
authors.initials: A
authors.lastname: Lupo
authors.forename: Pietro M
authors.initials: PM
authors.lastname: Ferraro
authors.forename: Franca
authors.initials: F
authors.lastname: Anglani
authors.forename: York
authors.initials: Y
authors.lastname: Pei
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Danza
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gambaro
mesh_terms: D016000:Cluster Analysis; D005190:Family; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics; D006801:Humans; D008297:Male; D007691:Medullary Sponge Kidney / Q000000981:diagnostic imaging / Q000235:genetics*; D019683:Penetrance; D014463:Ultrasonography
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor