Wilms tumor in patients with osteopathia striata with cranial sclerosis

Abstract

Germline pathogenic variants in AMER1 cause osteopathia striata with cranial sclerosis (OSCS: OMIM 300373), an X-linked sclerosing bone disorder. Female heterozygotes exhibit metaphyseal striations in long bones, macrocephaly, cleft palate, and, occasionally, learning disability. Male hemizygotes typically manifest the condition as fetal or neonatal death. Somatically acquired variants in AMER1 are found in neoplastic tissue in 15-30% of patients with Wilms tumor; however, to date, only one individual with OSCS has been reported with a Wilms tumor. Here we present four cases of Wilms tumor in unrelated individuals with OSCS, including the single previously published case. We also report the first case of bilateral Wilms tumor in a patient with OSCS. Tumor tissue analysis showed no clear pattern of histological subtypes. In Beckwith-Wiedemann syndrome, which has a known predisposition to Wilms tumor development, clinical protocols have been developed for tumor surveillance. In the absence of further evidence, we propose a similar protocol for patients with OSCS to be instituted as an initial precautionary approach to tumor surveillance. Further evidence is needed to refine this protocol and to evaluate the possibility of development of other neoplasms later in life, in patients with OSCS.

Wilms tumour surveillance in at-risk children: Literature review and recommendations from the SIOP-Europe Host Genome Working Group and SIOP Renal Tumour Study Group

“…OSCS is an X-linked condition caused by germline loss-of-function variants affecting the AMER1 (WTX) gene. Currently, WT has been reported in four female heterozygotes [104,105], and bilateral nephrogenic rests were reported at autopsy in a male patient with OSCS [106]. Although two published OSCS cohorts, including 17 and 22 liveborn patients, respectively, did not report childhood tumours [107,108], we consider WT surveillance to be justifiable based on the well-established role of AMER1/WTX in WT development [109].…”

The phenotypic spectrum of AMER1‐related osteopathia striata with cranial sclerosis: The first Canadian cohort

“…Most recent publications have described other multisystem findings including Wilms tumor (Bach et al, 2020;Gear & Savarirayan, 2021;Mi et al, 2020). As seen in Tables 1 and 2 and Figure Paternal transmission of OSCS has been described twice (Ciceri et al, 2013;Mi et al, 2020).…”

“…aReview of approximately 90 individuals reported with OS-CS and an AMER1 pathogenic variants. b Extrapolated from recently published data(Bach et al, 2020).…”

Wilms tumour occurring in a patient with osteopathia striata with cranial sclerosis: A still unsolved biological question

“…3 Somatic mutations in AMER1 are found in 7-29% of Wilms tumours (WT). [4][5][6][7] To date, and to the best of our knowledge, just five cases of paediatric tumours, four WT and one hepatoblastoma, have been reported in patients with OSCS [8][9][10] despite two large studies investigating cohorts of patients (including adults) with OSCS did not find an increased risk of cancer. 3,11 Herein, we report a clinical and molecular description of an additional girl affected by OSCS who developed a WT.…”

“…Paola Quarello 1,2 Daniela Perotti 3 Diana Carli 1,2 Elisa Giorgio 5,6,7 Fabio Sirchia 6,7,8 Alfredo Brusco 5,9 Giovanni Battista Ferrero 10 Alessandro Mussa 2,4 Manuela Spadea 1 Sara Ciceri 3…”