Clinical management of patients with ASXL1 mutations and Bohring-Opitz syndrome, emphasizing the need for Wilms tumor surveillance.
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 We report on eight previously unpublished patients with Bohring-Opitz syndrome caused by an apparent or confirmed de novo mutation in ASXL1.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.
Division of Human Genetics, Cincinnati Children's Hospital, Cincinnati, Ohio.
Bianca
B
Russell
National Human Genome Research Institute, National Institute of Health, Bethesda, Maryland.
Jennifer J
JJ
Johnston
National Human Genome Research Institute, National Institute of Health, Bethesda, Maryland.
Leslie G
LG
Biesecker
Medical Genetics Institute, Cedars Sinai Medical Center, Division of Medical Genetics, Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California.
Nancy
N
Kramer
Section of Medical Genetics, Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
Angela
A
Pickart
Section of Medical Genetics, Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
William
W
Rhead
Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts.
Wen-Hann
WH
Tan
Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts.
Catherine A
CA
Brownstein
Greenwood Genetic Center, Columbia, South Carolina.
L
L
Kate Clarkson
Greenwood Genetic Center, Columbia, South Carolina.
Amy
A
Dobson
Laboratory of Pathology, National Cancer Institute, National Institute of Health, Bethesda, Maryland.
Avi Z
AZ
Rosenberg
Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia.
Samantha A Schrier
SA
Vergano
Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia.
Benjamin M
BM
Helm
Clinical Genetics Service, Nottingham University Hospitals Trust, Nottingham, United Kingdom.
Rachel E
RE
Harrison
Medical Genetics Institute, Cedars Sinai Medical Center, Division of Medical Genetics, Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California.
John M
JM
Graham
D000015:Abnormalities, Multiple / Q000235:genetics; D019046:Bone Marrow Neoplasms / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics*
C473949:ASXL1 protein, human; D012097:Repressor Proteins
ASXL1; Bohring-Opitz syndrome; Wilms tumor; cyclic vomiting; failure to thrive; hypertrichosis; intellectual disability; myopia; nevus flammeus