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

Angela L Duker,Christy Jordan,Michael B Bober,Louise Thompson,Carissa M Baker-Smith,Ricki S Carroll,Tim Niiler,David A Parry,Dagmar Kinderman

doi:10.1186/s13023-021-01852-y

Abstract

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.

Highlights

Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is the most common form of primordial dwarfism, caused by bialleic mutations in the pericentrin gene (PCNT)
To systematically ascertain the medical problems associated with MOPDII and other forms of microcephalic primordial dwarfism (MPD), a Primordial Dwarfism Registry was established in 2008 at the Alfred I. duPont Hospital for Children
One individual had a clinical diagnosis of MOPDII with classic features and MOPDII comorbidities, but did not have molecular testing as he died before it was clinically available

Summary

Introduction

Microcephalic 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. The frequency and extent of the vasculopathy was unclear To help address this question, a vascular substudy was initiated within our Primordial Dwarfism Registry. Aside from the classic features of severe pre- and post-natal growth failure together with microcephaly, individuals with MOPDII have characteristic facial features, skeletal dysplasia, abnormal dentition, and can develop insulin resistance as well as truncal obesity [2, 7,8,9,10,11]. Care has changed dramatically over the past decade for individuals with this diagnosis, and has become more proactive than reactive in some domains, as associated medical conditions became known and screening for these issues could be initiated. Appropriate charts are available for monitoring of growth [17, 18]

Methods

Results

Discussion

Conclusion