Endocrine Abstracts

JOINT5

Background: Neurofibromatosis type 1 (NF1) is a common genetic condition (estimated prevalence at 1:3000 live births) and 0.1-5.7% of patients with NF1 will develop pheochromocytomas and paragangliomas in their lifetime. However, other causes of hypertension (HT) in the young among these patients could be presented and polycystic liver disease is not a part of NF1 syndrome. While autosomal recessive polycystic kidney disease (ARPKD) caused by biallelic pathogenic variants in the polycystic kidney and hepatic disease 1 (PKHD1) gene are rare (estimated prevalence at 1:20,000 live births), the frequency of heterozygous carrier state of PKHD1 gene is relatively common at 1 in 70 among general population. Polycystic liver disease had been described among patients with heterozygotic PKHD1 variant. We herein report a rare case of an NF1 patient who presented with HT in the young and incidental finding of polycystic liver disease.

Case Report: A 37-year-old Thai patient with history of NF-1 (clinically diagnosed at the age of 20 from presence of café au lait spots and neurofibromas) consulted with HT in the young for 2 years without other symptoms. No family history of hypertension or other genetic disorders had been reported. Abdominal computed tomography revealed polycystic liver disease and a simple renal cyst with normal both adrenal glands. Laboratory studies showed normal results. Whole exome sequencing (WES) confirmed 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 identified other causes of HT, co-occurrence of NF1 and HT-associated heterozygotic PKHD1 variant were diagnosed in this patient.

Conclusions: Our case highlights the diagnostic challenges of atypical phenotypes among individuals with NF1 might depend on the background of other genes. With increasing affordability of WES, its utility in uncovering the possibility of being affected by two inherited genetic conditions should be considered when findings are incompatible with the primary disease. The co-occurrence of NF1 and PKHD1 variants by chance or causative relationship should be further investigated in the future.