TSC2/PKD1 contiguous gene syndrome, with emphasis on a case with an atypical mild polycystic kidney phenotype and a novel genetic variant

About 80% of patients with tuberous sclerosis complex (TSC) present renal involvement, usually as angiomyolipomas followed by cystic disease. An early diagnosis of polycystic kidney disease (PKD) in such patients is frequently related to the TSC2/PKD1 contiguous gene syndrome (PKDTS). Molecular confirmation of PKDTS is important for a prompt diagnosis, which can be complicated by the phenotypic heterogeneity of PKD and the absence of a clear phenotype–genotype correlation. Herein, we report three PKDTS pediatric patients. The case 3 did not present a classic PKDTS phenotype, having only one observable cyst on renal ultrasound at age 4 and multiple small cysts on magnetic resonance imaging at age 15. In this patient, chromosomal microarray analysis showed a gross deletion of 230.8kb that involved TSC2, PKD1 and 13 other protein-coding genes, plus a heterozygous duplication of a previously undescribed copy number variant of 242.9kb that involved six protein-coding genes, including SSTR5, in the 16p13.3 region. Given the observations that the case 3 presented the mildest renal phenotype, harbored three copies of SSTR5, and the reported inhibition of cystogenesis (specially in liver) observed with somatostatin analogs in some patients with autosomal dominant PKD, it can be hypothesized that other genetic factors as the gene dosage of SSTR5 may influence the PKD phenotype and the progression of the disease; however, future work is needed to examine this possibility. Un 80% de los pacientes con complejo de esclerosis tuberosa (CET) presentan afectación renal, generalmente angiomiolipomas, seguidos de enfermedad quística. Un diagnóstico temprano de la enfermedad renal poliquística (ERP) en estos pacientes se relaciona con frecuencia con el síndrome de genes contiguos TSC2/PKD1 (PKDTS). La confirmación molecular de PKDTS es importante para establecer un diagnóstico oportuno, que puede complicarse por la heterogeneidad fenotípica de PKD y la ausencia de una clara correlación entre fenotipo y genotipo. En este artículo presentamos los casos de 3 pacientes pediátricos con PKDTS. El caso 3 no presentó un fenotipo PKDTS clásico, con solo un quiste observable en la ecografía renal a los 4 años y numerosos quistes pequeños en la resonancia magnética a los 15 años. En este paciente, el análisis de microarreglos para análisis cromosómico global mostró una eliminación total de 230,8kb que involucró a TSC2,PKD1 y otros 13 genes codificantes de proteínas, más una duplicación