It appears (as with many mutated genes) that a somatic mutation can lead to a form of cancer and the de novo mutation to a serious disease (syndrome). There is no evidence that children with BOS/de novo mutation in the ASXL1 gene will also have cancer.
However, there are cases of medulloblastoma (brain tumor) (Hasting et al. 2010), Wilms tumor (tumor of the kidney) (Russell et al. 2015 and 2023) as well as hepatoblastoma (liver cancer) occurred in Bohring-Opitz Syndrome (Russell et al. 2023; Patel et al. 2024).
Screening guidelines
Wilms tumor
Because of the 7% incidence of a renal neoplastic* process in patients with Bohring-Opitz syndrome, an association between BOS and bilateral Wilms Tumor is suspected. Therefore, these screening recommendations (Russell et al. 2015) have been published to detect the development of Wilms tumor in children with Bohring-Opitz Syndrome:
- Abdominal ultrasonography of kidney every three months in the first 8 years of life
Hepatoblastoma
Hepatoblastoma is a very rare malignant liver cancer occurring in infants and children, and can spread to other areas of the body. If early identified and treated, hepatoblastoma can be typically cured.
Up to date, there are three individuals diagnosed with hepatoblastoma described in the medical literature. Additional to the first reported case of hepatoblastoma (Russell et al. 2023), two more patients were described recently (Patel et al. 2024).
Patel et al. proposed liver tumor surveillance may be warranted for children with Bohring-Opitz Syndrome at young ages, including blood testing for alpha-fetoprotein (AFP) levels.
Even though the risk of hepatoblastoma in individuals with Bohring-Opitz is less than 1%, the occurrence of this cancer has led to update the tumor screening guidelines for Bohring-Opitz Syndrome. These guidelines are made by the ARRE Foundation Medical and Scientific Advisory Board, including Dr. Bianca Russell (University of California, Los Angeles) and Dr. Wen-Hann Tan (Boston Children’s Hospital) who are clinical geneticists with longstanding clinical research interests in Bohring-Opitz Syndrome. The screening recommendations for hepatoblastoma are:
- Abdominal ultrasonography of liver every three months from birth to eight years
- Discussion of the following additional screening options with your child’s care team:
- Measurement of alpha-fetoprotein (AFP) via blood draw every three months until age five
- Continuation of ultrasound screening past age 8 at a reduced frequency (e.g. every six months)
To avoid additional burdens, both abdominal screenings for Wilms tumor and hepatoblastoma can be done in one appointment, as long as it is guaranteed that liver as well as kidney are displayed at the ultrasonography.
*renal (=kidney) neoplastic (neoplasm = abnormal mass of tissue that forms when cells grow and divide more than they should or do not die when they should). Neoplasms may be benign (not cancer) or malignant (cancer).
Resources:
- Updated tumor screening guidelines by the ARRE foundation
- Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Health Professional Version and Patient Version
- Role of Asxl1 in kidney podocyte development via its interaction with Wtip
- Wilms tumor screening recommended for some patients with Bohring-Opitz Syndrome
- Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo
- Lipofibromatosis accompanied by several congenital anomalies, report of a rare case
Further read:
Bohring-Opitz Syndrome 