Status:Not yet recruiting
Keywords:Malformations , Cerebral , Cavernous , Hereditary , Hemorrhagic , Telangiectasia
Specialty:Hereditary Hemorrhagic Telangiectasia
Hereditary vascular malformation syndromes such as Cerebral Cavernous Malformations (CCM) or Hereditary Hemorrhagic Telangiectasia (HHT) include problems due to abnormal blood vessels that result from inherited mutations. The mutations responsible for these abnormalities are found in all blood vessels of the patients, yet only a minority of blood vessels actually become abnormal. In addition to the genetic mutation, other factors must influence a given blood vessel to form an abnormality at a given site. While the genetic predisposition may be difficult to eliminate in treating these patients, if specific triggers can be identified that cause malformations to develop, modifying these triggers may improve the disease.
This study is designed to carefully characterize the extent and severity of blood vessel abnormalities in patients with either CCM or HHT and correlate disease severity with a broad panel of blood and urine markers directed against a variety of potential triggers that are known to influence blood vessel behavior. Those markers that are consistently elevated in patients with more severe disease will imply a potential cause for disease worsening. Any markers that are found more often in those with mild disease will imply a potential protective effect against disease.
The study is designed as a cross-sectional observational cohort study in which participants will provide only a single set of samples to be correlated at that point in time with their symptoms and with testing done to identify the extent and severity of their blood vessel abnormalities.
This is an observational, non-randomized cohort study designed to compare clinical disease severity with serum and urine biomarkers that may predict disease severity and indicate possible disease mechanisms for further study and potential treatment. The study will consist of two cohorts of patients, one for each of the two diseases under study. Patients will be enrolled at either of the two collaborating centers, the University of Utah or the University of New Mexico. Patients enrolled in New Mexico will be supervised by the local IRB.
1. A diagnosis of either familial cerebral cavernous malformation (fCCM) or definite hereditary hemorrhagic telangiectasia (HHT).
1A: fCCM diagnosis: either clinical or genetic evidence of familial CCM - clinical: MRI diagnosis of CCM based on typical lesion characteristics AND evidence of familial disease (either a first degree relative with a diagnosis of CCM, OR the presence of multiple CCM lesions by MRI). Genetic: presence of a pathologic mutation of either KRIT1 (CCM1), Malcavernin (CCM2), or PDCD10 (CCM3).
1B: HHT diagnosis: either clinical or genetic evidence of HHT - clinical: the presence of 3 or more of the 4 Curaçao criteria - i) spontaneous epistaxis, ii) multiple typical mucocutaneous telangiectasias, iii) arteriovenous malformation of either brain, lung, liver or GI tract, and iv) first degree relative with diagnosis of definite HHT. Genetic: presence of a pathologic mutation of either endoglin, ACVRL1, or SMAD4.
2. Age 7 or greater.
3. Willing to give consent (age 18 or older), or assent to parental/guardian permission (age 7-17).
4. Measures of disease severity are known and available.
4A. CCM: a brain MRI has been performed within the past 12 months, or will be performed within the next 2 months.
4B. HHT: an epistaxis severity score (ESS) is available, the results of a previous imaging evaluation for brain AVM are available, and screening for lung AVM (by either contrast echocardiography, chest CT, or chest MRI) has been performed in the past 24 months.
1. The presence of any active infection or malignancy felt to impact serum markers of inflammation or cytokines.