Alternative titles; symbols
SNOMEDCT: 765331004; ORPHA: 88924;
Cytogenetic location: 16p13.3 Genomic coordinates (GRCh38): 16:1-7,800,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 16p13.3 | Polycystic kidney disease, infantile severe, with tuberous sclerosis | 600273 | Autosomal dominant | 4 |
A number sign (#) is used with this entry because of evidence that infantile severe polycystic kidney disease with tuberous sclerosis (PKDTS) is a contiguous gene deletion syndrome involving the PKD1 (601313) and TSC2 (191092) genes on chromosome 16p13.3.
In a small but well-documented minority of patients with tuberous sclerosis (see 191100), a striking clinical picture of enlarged and polycystic kidneys has been recognized at birth or shortly thereafter (Wenzl et al., 1970; O'Callaghan et al., 1975; Stapleton et al., 1980). In these patients, the polycystic kidneys are characterized by a multitude of variably sized cysts closely resembling those more commonly seen in later life in the advanced stages of autosomal dominant polycystic kidney disease (PKD1; 173900). The PKD1 gene lies immediately adjacent to the gene on 16p that is mutant in one form of tuberous sclerosis (TSC2; 191092). In a group of 196 unrelated tuberous sclerosis patients, Brook-Carter et al. (1994) had information on renal ultrasound examination in 45; 18 of these had renal cysts (in conjunction with angiomyolipomata in 11 cases). Only 1 was noted to have grossly enlarged polycystic kidneys within the first few months of life. After the discovery of a deletion involving both TSC2 and PKD1 in this patient, Brook-Carter et al. (1994) specifically ascertained other tuberous sclerosis patients who had presented during early infancy with severely polycystic kidneys. Absence of signs of tuberous sclerosis in parents and other family members suggested that all cases probably represented new mutations. All 6 patients had large deletions disrupting both TSC2 and PKD1. Deletions were found to inactivate PKD1, in contrast to the mutations reported in autosomal dominant polycystic kidney disease in which in each case abnormal transcripts have been detected. The TSC2 gene lies just distal to the PKD1 gene and has a genomic size of approximately 45 kb.
Brook-Carter, P. T., Peral, B., Ward, C. J., Thompson, P., Hughes, J., Maheshwar, M. M., Nellist, M., Gamble, V., Harris, P. C., Sampson, J. R. Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease: a contiguous gene syndrome. Nature Genet. 8: 328-332, 1994. [PubMed: 7894481] [Full Text: https://doi.org/10.1038/ng1294-328]
O'Callaghan, T. J., Edwards, J. A., Tobin, M., Mookerjee, B. K. Tuberous sclerosis with striking renal involvement in a family. Arch. Intern. Med. 135: 1082-1087, 1975. [PubMed: 1156071]
Stapleton, F. B., Johnson, D., Kaplan, G. W., Griswold, W. The cystic renal lesion in tuberous sclerosis. J. Pediat. 97: 574-579, 1980. [PubMed: 7420220] [Full Text: https://doi.org/10.1016/s0022-3476(80)80011-4]
Wenzl, J. E., Lagos, J. C., Albers, D. D. Tuberous sclerosis presenting as polycystic kidneys and seizures in an infant. J. Pediat. 77: 673-676, 1970. [PubMed: 5454714] [Full Text: https://doi.org/10.1016/s0022-3476(70)80211-6]