A case of being ‘double unlucky’

A 5-year-old girl presented with a history of global developmental delay and recurrent focal seizures since 2 years of age. Her parents had also noticed a progressive abdominal distension for the last 1 year. Physical examination revealed facial angiofibroma/adenoma sebaceum (Figure 1), blood pressure of 110/ 80 mmHg (between the 95th and 99th percentiles for age sex and height percentile) and a soft but distended abdomen with bilaterally palpable kidneys. Her laboratory investigations were unremarkable, and she had no proteinuria, microscopic haematuria or renal dysfunction. Imaging studies showed a bilateral nephromegaly with multiple cysts on ultrasonography (Figure 2) and periventricular tubers on computed tomography scan of the brain (Figure 3). In view of the presence of features of both autosomal dominant polycystic kidney disease (enlarged kidneys with multiple cysts) as well as tuberous sclerosis (facial angiofibroma/adenoma sebaceum and periventricular tubers) but absent family history of renal diseases and normal screening parental ultrasound, a clinical diagnosis of polycystic kidney disease 1/tuberous sclerosis complex 2 (TSC2) contiguous gene syndromes (PKDTS) was made. TSC2 (located at 16p13.3) and PKD1 (16p13.3) genes lie immediately adjacent to each other in a tail-to-tail configuration with ∼3 kb of genomic DNA in the intergenic region [1]. Mutation analysis has shown that 2–3% of TSC2 mutations are large genomic DNA deletions in which some part of both TSC2 and PKD1 are involved [2], leading to a novel contiguous gene syndrome PKDTS (Mendelian Inheritance of Mankind: 600273). In contrast with the typical TSC, the renal lesion in the PKDTS consists of PKD, which has an earlier onset and progresses more rapidly [3]. This feature of PKDTS also contrasts with isolated ADPKD, where onset is usually later and progression slower. To conclude, PKDTS is a distinct clinical entity and should be considered in patients with an early manifestation of PKD without a positive family history, but having clinical features of TSC.