Tuberous sclerosis and polycystic kidney disease in a 3-month-old infant

Abstract

Tuberous sclerosis (TSC) is an autosomal dominantly inherited multisystemic disease characterized by the development of hamartomas predominantly in brain and kidneys. The TSC2 gene for tuberous sclerosis is localized on chromosome 16p13.3 immediately adjacent to PKD1, the gene for autosomal dominant polycystic kidney disease (ADPKD). A TSC2-PKD1 contiguous gene syndrome caused by chromosomal microdeletions disrupting both the TSC2 and PKD1 genes has been identified in patients with TSC and early-onset severe ADPKD. We report a 3-month-old Caucasian girl of non-consanguineous parents with TSC and early manifestation of ADPKD. She presented with right-sided focal seizures, two small hypopigmented areas on the left flank, and elevated blood pressure requiring antihypertensive treatment. Brain magnetic resonance imaging revealed typical signs of tuberous sclerosis and abdominal ultrasonography showed bilaterally enlarged kidneys with multiple cysts resembling those seen in ADPKD. There was no family history of renal disease or of tuberous sclerosis. Findings were highly suspicious of TSC2-PKD1 contiguous gene syndrome. Using fluorescence in situ hybridization and plasmid probe CW23, which spans the adjacent 3' regions of TSC2 and PKD1 genes, we identified a submicroscopic deletion on only one of the chromosomes 16p13.3, thus permitting the diagnosis of the TSC2-PKD1 contiguous gene syndrome.

The economic burden of tuberous sclerosis complex in UK patients with renal manifestations: a retrospective cohort study in the clinical practice research datalink (CPRD)

“…A less common presentation of renal cysts involves co-manifestation with polycystic kidney disease, characterized by a multitude of symptomatic large cysts and poor patient prognoses 29 . The manifestation of renal cysts occurs due to the close proximity between the TSC2 locus and the polycystic kidney disease gene (PKD1), which are pre-disposed to contiguous deletions 33 . TSC guidelines recommend regular monitoring and surveillance of TSC patients 1 , and annual screening of those with established renal manifestations 26 .…”

Tuberous Sclerosis Complex With Polycystic Kidney Disease of the Adult Type: the TSC2/ADPKD1 Contiguous Gene Syndrome

“…Recently a similar adjacent gene syndrome in an infant has been successfully studied by means of fluorescent in situ hybridization technique, using a specific plasmid probe spanning the adjacent 3′ regions of TSC2 and PKD1 genes. 36 Finally, given the autosomal dominant mode of inheritance of both TSC and ADPKD and the total lack of any family history of both these conditions, this patient most likely represents a sporadic case. Sporadic cases do occur and constitute two thirds of the patients afflicted with TSC, 40 75% of whom appear to be caused by TSC2 gene mutations, 41 and 10% of the patients with polycystic kidney disease of the adult type, 9 respectively.…”

Selected Case From the Arkadi M. Rywlin International Pathology Slide Series

“…1,2,[24][25][26] "Glomerulocystic kidney," or "glomerulocystic pattern of kidney involvement," is a term for referring to the kidneys with glomerular cysts as a major pathologic feature, which may characterize complex inheritable malformation syndromes (syndromic GCK), such as TSC, orofaciodigital syndrome type I, brachymesomelia renal syndrome, trisomy 13, short-rib-polydactyly syndrome (Majewski type and Saldino-Noonan type), Jeune asphyxiating thoracic dystrophy syndrome, Zellweger cerebrohepatorenal syndrome, and familial juvenile nephronophtisis. 1,[27][28][29][30][31] It is the close company that these loci keep that make them vulnerable to a deletion/mutation that may compromise the integrity of both, and set the stage for altered primary cilium, the organelle primarily responsible for functional cell polarity and cystogenesis. Occasionally, GCK (sporadic GCK) may be featured by other diseases, both congenital (such as hypothyroidism, retinitis pigmentosa, cerebral vascular malformation) and acquired (drug induced or ischemic as in progressive systemic sclerosis).…”