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

Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia ("POTS" -- Postural Orthostatic Tachycardia Syndrome)Later in Life -- a Retrospective Analysis

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 Overview

• Status: Completed
• Conditions: Venous Insufficiency; Postural Orthostatic Tachycardia Syndrome; Dysautonomia; Ehlers Danlos Syndrome; External Hydrocephalus

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.

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• United States
  • Texas
    • Colleyville, Texas, United States, 76034
      • POTS Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• 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.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Ehlers-Danlos patients; Patients with diagnosed or suspected Classic or Hypermobile Ehlers-Danlos Syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Head Circumference in Ehlers-Danlos patients (retrospectively), between the ages of birth to 15 months of age.	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.	Retrospectively, between patients' birth to 15 months of age

Collaborators and Investigators

• Sponsor: Genetic Disease Investigators
• Investigators: Principal Investigator: Diana L Driscoll, O.D., Genetic Disease Investigators

Publications and helpful links

General Publications

• Alvarez LA, Maytal J, Shinnar S. Idiopathic external hydrocephalus: natural history and relationship to benign familial macrocephaly. Pediatrics. 1986 Jun;77(6):901-7.
• 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. doi: 10.3171/SPI-07/12/601.
• Kumar R. External hydrocephalus in small children. Childs Nerv Syst. 2006 Oct;22(10):1237-41. doi: 10.1007/s00381-006-0047-1. Epub 2006 Mar 23.
• Levy HP. Hypermobile Ehlers-Danlos Syndrome. 2004 Oct 22 [updated 2018 Jun 21]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1279/

Helpful Links

• Clinical trials by Pretty ill
• click here for information on all clinical studies at POTS Care

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: June 5, 2011
• First Submitted That Met QC Criteria: June 5, 2011
• First Posted (Estimated): June 7, 2011

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Dysautonomia; Postural orthostatic tachycardia syndrome; Ehlers Danlos Syndrome; External Communicating Hydrocephalus; Chronic cerebrospinal venous insufficiency
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Skin Abnormalities; Orthostatic Intolerance; Collagen Diseases; Syndrome; Tachycardia; Postural Orthostatic Tachycardia Syndrome; Primary Dysautonomias; Autonomic Nervous System Diseases; Venous Insufficiency; Hydrocephalus; Ehlers-Danlos Syndrome
• Other Study ID Numbers: 61/3528