Co-occurrence of Neurofibromatosis Type 1 and Polycystic Liver Disease: A Case of Hypertension with PKHD1 Variant

BACKGROUND Neurofibromatosis type 1 (NF1) is a common genetic condition; 0.1-5.7% of patients with NF1 will develop pheochromocytomas in their lifetime. However, other causes of hypertension (HT) in young patients can be present, and polycystic liver disease is not a part of NF1 syndrome. Polycystic liver disease had been described among patients with heterozygotic polycystic kidney and hepatic disease 1 (PKHD1) variant. We report a rare case of a young patient with NF1 who presented with HT and polycystic liver disease. CASE REPORT A 37-year-old Thai woman with history of NF-1 (clinically diagnosed at the age of 20 years from presence of cafe-au-lait spots and neurofibromas) had HT for 2 years without other symptoms. Abdominal computed tomography revealed polycystic liver disease and a simple renal cyst with both adrenal glands normal. Laboratory studies showed normal results. Whole-exome sequencing (WES) confirmed the molecular diagnosis of NF1 with heterozygous pathogenic variants c.5268+1G>A of NF1 and heterozygous pathogenic variants c.7594_7597del of PKHD1 gene. Given the results of genetic testing and no other identified causes of HT, co-occurrence of NF1 and HT-associated heterozygotic PKHD1 variant was diagnosed. CONCLUSIONS Our case highlights the diagnostic challenges of atypical phenotypes among individuals with NF1, which can depend on the background of other genes. With increasing affordability of WES, its utility in uncovering the possibility of being affected by 2 inherited genetic conditions should be considered when findings are incompatible with the primary disease.