Partial deletion of ANKRD11 results in the KBG phenotype distinct from the 16q24.3 microdeletion syndrome.

Abstract

KBG syndrome (OMIM 148050) is a very rare genetic disorder characterized by macrodontia, distinctive craniofacial abnormalities, short stature, intellectual disability, skeletal, and neurologic involvement. Approximately 60 patients have been reported since it was first described in 1975. Recently mutations in ANKRD11 have been documented in patients with KBG syndrome, and it has been proposed that haploinsufficiency of ANKRD11 is the cause of this syndrome. In addition, copy number variation in the 16q24.3 region that includes ANKRD11 results in a variable phenotype that overlaps with KBG syndrome and also includes autism spectrum disorders and other dysmorphic facial features. In this report we present a 2½-year-old African American male with features highly suggestive of KBG syndrome. Genomic microarray identified an intragenic 154 kb deletion at 16q24.3 within ANKRD11. This child's mother was mosaic for the same deletion (present in approximately 38% of cells) and exhibited a milder phenotype including macrodontia, short stature and brachydactyly. This family provides additional evidence that ANKRD11 causes KBG syndrome, and the mild phenotype in the mosaic form suggests that KBG phenotypes might be dose dependent, differentiating it from the more variable 16q24.3 microdeletion syndrome. This family has additional features that might expand the phenotype of KBG syndrome.

• Authors: Mohamed Khalifa, Jennifer Stein, Lance Grau, Valery Nelson, Jeanne Meck, Swaroop Aradhya, John Duby
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 161A Issue 4 Pg. 835-40 (Apr 2013) ISSN: 1552-4833 [Electronic] United States
• PMID: 23494856 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2013 Wiley Periodicals, Inc.

Chemical References

• ANKRD11 protein, human
• Repressor Proteins

Topics

• Abnormalities, Multiple (diagnosis, genetics)
• Bone Diseases, Developmental (diagnosis, genetics)
• Chromosome Deletion
• Chromosomes, Human, Pair 16
• Comparative Genomic Hybridization
• Diagnosis, Differential
• Facies
• Female
• Gene Deletion
• Humans
• In Situ Hybridization, Fluorescence
• Infant
• Intellectual Disability (diagnosis, genetics)
• Male
• Mosaicism
• Phenotype
• Repressor Proteins (genetics)
• Syndrome
• Tooth Abnormalities (diagnosis, genetics)