Microcephalic osteodysplastic primordial dwarfism type II is associated with global vascular disease

Orphanet Journal of Rare Diseases

Carissa M. Baker-Smith¹  Dagmar Kinderman²  Tim Niiler³  David A. Parry⁴  Christy Jordan⁵  Angela L. Duker⁶  Michael B. Bober⁶  Ricki S. Carroll⁶  Louise Thompson⁷ 

[1] Department of Cardiology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA;Department of Research, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA;Gait Laboratory, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA;MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK;Potentials Foundation, Sandoval, IL, USA;Skeletal Dysplasia Program, Division of Orthogenetics, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Road, 19803, Wilmington, DE, USA;The South East of Scotland Clinical Genetic Service, Western General Hospital, Edinburgh, UK;

关键词: MOPDII;    Primordial dwarfism;    Vascular disease;    Moyamoya;    Aneurysm;    Stroke;    Myocardial infarction;    Diabetes;    Chronic kidney disease;    Kaplan–Meier;   

DOI  :  10.1186/s13023-021-01852-y

来源: Springer

【 摘 要 】

BackgroundMicrocephalic osteodysplastic primordial dwarfism type II (MOPDII) is the most common form of primordial dwarfism, caused by bialleic mutations in the pericentrin gene (PCNT). Aside from its classic features, there are multiple associated medical complications, including a well-documented risk of neurovascular disease. Over the past several years, it has become apparent that additional vascular issues, as well as systemic hypertension and kidney disease may also be related to MOPDII. However, the frequency and extent of the vasculopathy was unclear. To help address this question, a vascular substudy was initiated within our Primordial Dwarfism Registry.ResultsMedical records from 47 individuals, living and deceased, ranging in age from 3 to 41 years of age were interrogated for this purpose. Of the total group, 64% were diagnosed with moyamoya, intracranial aneurysms, or both. In general, the age at diagnosis for moyamoya was younger than aneurysms, but the risk for neurovascular disease was throughout the shortened lifespan. In addition to neurovascular disease, renal, coronary and external carotid artery involvement are documented. 43% of the total group was diagnosed with hypertension, and 17% had myocardial infarctions. A total of 32% of the entire cohort had some form of chronic kidney disease, with 4% of the total group necessitating a kidney transplant. In addition, 38% had diabetes/insulin resistance. Ages of diagnoses, treatment modalities employed, and location of vasculopathies were notated as available and applicable, as well as frequencies of other comorbidities.ConclusionsIt is now clear that vascular disease in MOPDII is global and screening of the cardiac and renal vessels is warranted along with close monitoring of blood pressure. We recommend a blood pressure of 110/70 mmHg as a starting point for an upper limit, especially if the individual has a history of neurovascular disease, chronic kidney disease and/or diabetes. Additionally, providers need to be at high alert for the possibility of myocardial infarctions in young adults with MOPDII, so that appropriate treatment can be initiated promptly in an acute situation.

【 授权许可】

CC BY