Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia Later in Life

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Genetic Disease Investigators.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Genetic Disease Investigators
ClinicalTrials.gov Identifier:
NCT01367977
First received: June 5, 2011
Last updated: NA
Last verified: June 2011
History: No changes posted
  Purpose

It is known that 33-50% of Classic and Hypermobile Ehlers-Danlos Syndrome patients eventually develop dysautonomia, otherwise known as "POTS" (Postural Orthostatic Tachycardia Syndrome). Some of these patients develop dysautonomia as a result of a retroflexed odontoid, Chiari 1 Malformation or cranial settling and the resulting basilar impression. Many Ehlers-Danlos patients suffer with the same symptomology with no evidence of a cause according to MRI imaging.

It is the author's hypothesis that low-level External Communicating Hydrocephalus appears to be responsible for the constellation of autonomic and cranial nerve symptoms, and if present in the very young, an analysis of head circumference growth in the first 15 months of life should reflect abnormally rapid head growth, supporting this hypothesis.


Condition
Ehlers Danlos Syndrome
External Hydrocephalus
Dysautonomia
Postural Orthostatic Tachycardia Syndrome
Venous Insufficiency

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia ("POTS" -- Postural Orthostatic Tachycardia Syndrome)Later in Life -- a Retrospective Analysis

Resource links provided by NLM:


Further study details as provided by Genetic Disease Investigators:

Primary Outcome Measures:
  • Measurement of Head Circumference in Ehlers-Danlos patients (retrospectively), between the ages of birth to 15 months of age. [ Time Frame: Retrospectively, between patients' birth to 15 months of age ] [ Designated as safety issue: No ]
    Measurements of head circumferences, weight and length of children (retrospectively), will be compared to "normals" as established by the U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC), 2008.


Estimated Enrollment: 25
Study Start Date: May 2011
Estimated Study Completion Date: November 2011
Estimated Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
Ehlers-Danlos patients
Patients with diagnosed or suspected Classic or Hypermobile Ehlers-Danlos Syndrome

Detailed Description:

It is known that 33-50% of Classic and Hypermobile Ehlers-Danlos Syndrome patients eventually develop dysautonomia, otherwise known as "POTS" - Postural Orthostatic Tachycardia Syndrome. Some of these patients develop dysautonomia as a result of a retroflexed odontoid, Chiari 1 Malformation or cranial settling and the resulting basilar impression. However, many Ehlers-Danlos patients suffer with the same symptomology with no evidence of cause according to MRI imaging. It is the author's hypothesis that low-level External Communicating Hydrocephalus appears to be responsible for the constellation of autonomic and cranial nerve symptoms, and if present in the very young, an analysis of head circumference growth in the first 15 months of life should reflect abnormally rapid head growth, supporting the hypothesis.

The investigators will evaluate the head circumference of Ehlers-Danlos patients who display dysautonomia later in life. The head circumference analyzed will be from birth to approximately 15 months of age, as the sutures of the skull generally fuse between 16 and 18 months. Additionally, pediatricians do not usually measure head circumference routinely beyond this age.

In a small subset of Ehlers-Danlos patients who developed postural orthostatic tachycardia syndrome in their childhood or teen years, retrospective analysis of their head circumferences indicates such megalocephaly. On average, the children's heads were found to increase from approximately the 35th percentile to over the 90th percentile. Their weights and lengths did not increase in the same fashion, although some of the children remained in the higher percentages for their length.

A review of literature indicates that studies of children with megalocephaly (not necessarily having the diagnosis of Ehlers-Danlos) were considered to have a benign condition ("Benign External Communicating Hydrocephalus") because CT's at the age of 2 or 3 years appeared normal and neurological exams also appeared normal. However, studies have also shown that a large percentage of these children exhibited delayed motor development and some of them had delayed speech development.In some studies these children were treated with Diamox, and in other studies the children were merely observed.

It is the author's hypothesis that delayed motor development found in Ehlers-Danlos children is due at least in part to hydrocephalus, and not merely due to flexible joints, as previously surmised.

It is the author's contention that mild symptoms of irritability, headaches, sleep disorders, emotional "fits", and the later development of dysautonomia were never considered in these studies, yet are the likely symptoms of a low level of pressure that continued to be exerted on the brains of these children.

High pressure on the brain (even if subtle) could be evidence of congenital CCSVI (cerebrospinal venous insufficiency) or increased CSF (cerebral spinal fluid) production, or the poor drainage of cerebral spinal fluid, or both. Retrospective examination of skull expansion is a necessary step to ascertain these possibilities, allowing for early treatment and the hope of avoidance of the neurological symptoms, and often disabling effects of dysautonomia (and/or multiple sclerosis). It is the author's contention that "Benign External Hydrocephalus" is not a benign condition.

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with Classic or Hypermobile Ehlers-Danlos Syndrome with dysautonomia, found through social media forums, internet advertising, local support groups, physicians working with this subset of patients.

Criteria

Inclusion Criteria:

  • Diagnosis, or suspected diagnosis of Classic or Hypermobile Ehlers-Danlos Syndrome and dysautonomia
  • Must be able to present their head circumferences, weight and length for the first 15 months of their lives

Exclusion Criteria:

  • Patients unable to present their head circumferences, weight and length for the first 15 months of their lives
  • Patients with dysautonomia due to stroke of the brain stem
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01367977

Contacts
Contact: Diana L Driscoll, O.D. 817.416.0333 DrDiana@Prettyill.com
Contact: Richard A Driscoll, O.D. 817.431.4900 RDriscoll@TotalEyeCare.net

Locations
United States, Texas
Total Eye Care Recruiting
Colleyville, Texas, United States, 76034
Contact: Richard A Driscoll, O.D.    817-416-0333    RDriscoll@TotalEyeCare.net   
Contact: Diana L Driscoll, O.D.    817.416.0333    DrDiana@Prettyill.com   
Sub-Investigator: Richard A Driscoll, O.D.         
Principal Investigator: Diana L Driscoll, O.D.         
Sponsors and Collaborators
Genetic Disease Investigators
Investigators
Principal Investigator: Diana L Driscoll, O.D. Genetic Disease Investigators
Study Director: Richard A Driscoll, O.D. Genetic Disease Investigators
  More Information

Additional Information:
Publications:
Responsible Party: Diana Driscoll, O.D., Study Director, Genetic Disease Investigators
ClinicalTrials.gov Identifier: NCT01367977     History of Changes
Other Study ID Numbers: 61/3528
Study First Received: June 5, 2011
Last Updated: June 5, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Genetic Disease Investigators:
Ehlers Danlos Syndrome
External Communicating Hydrocephalus
Dysautonomia
Postural orthostatic tachycardia syndrome
Chronic cerebrospinal venous insufficiency

Additional relevant MeSH terms:
Syndrome
Tachycardia
Ehlers-Danlos Syndrome
Postural Orthostatic Tachycardia Syndrome
Venous Insufficiency
Hydrocephalus
Autonomic Nervous System Diseases
Primary Dysautonomias
Disease
Pathologic Processes
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Intracranial Hypertension
Hemostatic Disorders
Hemorrhagic Disorders
Hematologic Diseases
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases
Skin Diseases
Orthostatic Intolerance

ClinicalTrials.gov processed this record on October 16, 2014