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J Hum Genet. 2019 Apr;64(4):291-296. doi: 10.1038/s10038-019-0565-9. Epub 2019 Jan 28.

WNT1-associated osteogenesis imperfecta with atrophic frontal lobes and arachnoid cysts.

Author information

1
Center of Excellence in Medical Genetics Research, Chiang Mai University; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand. dentaland17@gmail.com.
2
Dentaland Clinic, Chiang Mai, Thailand. dentaland17@gmail.com.
3
Department of Orthopaedic surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
4
Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
5
Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
6
Department of Anatomy and Cell Biology, University of Michigan, Ann Arbor, MI, USA.
7
Center of Excellence in Medical Genetics Research, Chiang Mai University; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
8
Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
9
Division of Genetics and Molecular Biology, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.

Abstract

A rare form of osteogenesis imperfecta (OI) caused by Wingless-type MMTV integration site family 1 (WNT1) mutations combines central nervous system (CNS) anomalies with the characteristic increased susceptibility to fractures. We report an additional case where arachnoid cysts extend the phenotype, and that also confirms the association of intellectual disabilities with asymmetric cerebellar hypoplasia here. Interestingly, if the cerebellum is normal in this disorder, intelligence is as well, analogous to an association with similar delays in a subset of patients with sporadic unilateral cerebellar hypoplasia. Those cases typically appear to represent vascular disruptions, and we suggest that most brain anomalies in WNT1-associated OI have vascular origins related to a role for WNT1 in CNS angiogenesis. This unusual combination of benign cerebellar findings with effects on higher functions in these two situations raises the possibility that WNT1 is involved in the pathogenesis of the associated sporadic cases as well. Finally, our patient reacted poorly to pamidronate, which appears ineffective with this form of OI, so that a lack of improvement is an indication for molecular testing that includes WNT1.

PMID:
30692598
DOI:
10.1038/s10038-019-0565-9
[Indexed for MEDLINE]

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