Expired Study
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Colleyville, Texas 76034


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.


Study summary:

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.


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


Study is Available At:


Original ID:

61/3528


NCT ID:

NCT01367977


Secondary ID:


Study Acronym:


Brief Title:

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


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


Overall Status:

Completed


Study Phase:

N/A


Genders:

Both


Minimum Age:

5 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Genetic Disease Investigators


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Observational


Study Design:

Observational Model: Case-Only, Time Perspective:


Number of Arms:

0


Number of Groups:

1


Total Enrollment:

21


Enrollment Type:

Actual


Overall Contact Information

Official Name:Diana L Driscoll, O.D.
Principal Investigator
Genetic Disease Investigators

Study Dates

Start Date:May 2011
Completion Date:April 2015
Completion Type:Actual
Primary Completion Date:April 2015
Primary Completion Type:Actual
Verification Date:April 2015
Last Changed Date:April 2, 2015
First Received Date:June 5, 2011

Study Outcomes

Outcome Type:Primary Outcome
Measure: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
Safety Issues:False
Description: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.

Study Interventions

There are no available Study Interventions

Study Arms

Study Arm Type:Other
Arm Name:Ehlers-Danlos patients
Description:Patients with diagnosed or suspected Classic or Hypermobile Ehlers-Danlos Syndrome

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Genetic Disease Investigators

Samples and Retentions

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.
Sample Method:Non-Probability Sample

Study References

Reference Type:Reference
Citation:Kumar R. External hydrocephalus in small children. Childs Nerv Syst. 2006 Oct;22(10):1237-41. Epub 2006 Mar 23.
PMID:16555081
Reference Type:Reference
Citation:Milhorat TH, Bolognese PA, Nishikawa M, McDonnell NB, Francomano CA. Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and chiari malformation type I in patients with hereditary disorders of connective tissue. J Neurosurg Spine. 2007 Dec;7(6):601-9.
PMID:18074684
Reference Type:Reference
Citation:Levy HP. Ehlers-Danlos Syndrome, Hypermobility Type. 2004 Oct 22 [updated 2012 Sep 13]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from http://www.ncbi.nlm.nih.gov/books/NBK1279/
PMID:20301456
Reference Type:Reference
Citation:Alvarez LA, Maytal J, Shinnar S. Idiopathic external hydrocephalus: natural history and relationship to benign familial macrocephaly. Pediatrics. 1986 Jun;77(6):901-7.
PMID:3714384

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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