Clinical management of patients with ASXL1 mutations and Bohring-Opitz syndrome, emphasizing the need for Wilms tumor surveillance.

Abstract

Bohring-Opitz syndrome is a rare genetic condition characterized by distinctive facial features, variable microcephaly, hypertrichosis, nevus flammeus, severe myopia, unusual posture (flexion at the elbows with ulnar deviation, and flexion of the wrists and metacarpophalangeal joints), severe intellectual disability, and feeding issues. Nine patients with Bohring-Opitz syndrome have been identified as having a mutation in ASXL1. We report on eight previously unpublished patients with Bohring-Opitz syndrome caused by an apparent or confirmed de novo mutation in ASXL1. Of note, two patients developed bilateral Wilms tumors. Somatic mutations in ASXL1 are associated with myeloid malignancies, and these reports emphasize the need for Wilms tumor screening in patients with ASXL1 mutations. We discuss clinical management with a focus on their feeding issues, cyclic vomiting, respiratory infections, insomnia, and tumor predisposition. Many patients are noted to have distinctive personalities (interactive, happy, and curious) and rapid hair growth; features not previously reported.

• Authors: Bianca Russell, Jennifer J Johnston, Leslie G Biesecker, Nancy Kramer, Angela Pickart, William Rhead, Wen-Hann Tan, Catherine A Brownstein, L Kate Clarkson, Amy Dobson, Avi Z Rosenberg, Samantha A Schrier Vergano, Benjamin M Helm, Rachel E Harrison, John M Graham Jr
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 167A Issue 9 Pg. 2122-31 (Sep 2015) ISSN: 1552-4833 [Electronic] United States
• PMID: 25921057 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• ASXL1 protein, human
• Repressor Proteins

Topics

• Abnormalities, Multiple (genetics)
• Bone Marrow Neoplasms (genetics)
• Child
• Child, Preschool
• Craniosynostoses (genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Humans
• Infant
• Intellectual Disability (genetics)
• Male
• Mutation (genetics)
• Repressor Proteins (genetics)
• Wilms Tumor (genetics)