Study of Quality of Life in Freeman-Sheldon Syndrome and Related Conditions

Terminated

• Conditions: Arthrogryposis; Depressive Disorder; Craniofacial Abnormalities; Posttraumatic Stress Disorder
• Interventions: Other: PTSD Checklist-Specific; Other: Modified Flanagan Quality of Life Scale; Other: Center for Epidemiologic Studies Depression Scale; Other: Functional Enquiry Form; Other: Strength, Joint ROM, Girth and Length Measurements; Other: Study Physical Examination; Other: PTSD, Depression, and FSS-Focused Examination; Other: Freeman-Sheldon Specific Quality of Life Survey; Other: Lactate, Glucose, and Adenosine Triphosphate Blood Levels

• Registration Number: NCT01307475
• Lead Sponsor: Freeman-Sheldon Research Group, Inc.

Brief Summary

Freeman-Sheldon syndrome (FSS) is a rare human neuromusculoskeletal disorder present before birth, involving primarily limb and craniofacial deformities.

The hypotheses in the present study of FSS and related conditions are: (1) FSS and related conditions are associated with higher rates of posttraumatic stress symptoms (PTSS), depression, and reduced quality of life than is observed in the general population; (2) persons close to an individual with FSS or related condition suffer similarly; and (3) current measures, which are single-disease specific (i.e., PTSS, depression, craniofacial deformities, or limb deformities), do not capture the unique picture of FSS and related conditions, which involve both limb and craniofacial deformities in an intellectually capable individual.

There have been no studies looking at quality of life associated with FSS. Some authors have looked at quality of life in persons with facial differences; other authors have looked at bone and joint problems. Many other authors have looked at PTSS and depression caused by health problems and bad medical experiences. No authors have looked at these problems when they happen together, as they do in FSS. Because of the above, there may be differences in patients that have FSS versus patients in previous quality of life studies. The study will also develop and validate an outcomes-based quality of life survey for FSS and related conditions.

Detailed Description

This study is a research project initiated by the graduate research student (Mikaela I. Poling) and assisted by the clinical genetics fellow and graduate student (Andrés Morales) in partial fulfilment the requirements for their Masters degrees in Clinical and Applied Physiology, under approval, direction, and supervision of the study PI (Rodger J. McCormick).

Mental Health and Congenital Deformities:

Apajasalo et al. (1998) found significantly decreased health-related quality of life versus controls among adults and youth ages with chondrodysplasias. Differences in adult scores were in the areas of mobility, usual activities, and sexual activity and discomfort. Youth scores differed more in school and hobbies and friends and physical appearance. Didierjean-Pillet (2002) stressed concern for aesthetics of reconstruction in consideration of psychiatric impacts of congenital deformities in psychosocial functioning. Nagata et al. (2008) found that 20% of mothers with children operated on for congenital disease were likely to have post-traumatic stress disorder (PTSD). They found that pro-active, effective participation in the child's care may alleviate PTSS. Vitale et al. (2005) found quality of life survey scores among clubfoot patients compatible with age-matched controls, in agreement with Roye (2001), and not correlated to radiograph appearance. They advised quality of life survey scores be primary endpoint in determining therapeutic outcome. Engell et al. (2007) found significant post-operative improvement in the Short Form-12 Health Survey physical component scale in congenital clubbed-foot patients in the Danish Twin Registry. Vitale et al. (2001) observed that tailored quality of life scales were required for paediatric orthopaedic populations. Hawkins and Radcliffe (2006) concluded there was a lack of appropriate and validated PTSD measures for paediatric patients. Part of this problem of lacking validated paediatric PTSD measures was likely do to non-comprehensive Diagnostic and Statistical Manual of Mental Disorders IV Text-Revision criteria.

Relevance to Current Study:

Because FSS-related deformities were more comprehensive, treatment-resistant, and associated with poorer clinical outcome, quality of life studies not including a subset of FSS patients may not be appropriate in the more challenging clinical picture of FSS-related deformities. In many conditions, disorder-specific quality of life measures (QLM) showed increased sensitivity and specificity over general QLMs and were important therapeutic tools to assess efficacy of and prioritise interventions. Results of disorder-specific QLMs were important predictors of clinical outcome.

Study Timeline

• Study Start: 2011-02
• Study First Submitted: 2011-02-27
• Study First Submitted QC: 2011-03-01
• Study First Posted: 2011-03-03
• Status Verified: 2017-04
• Primary Completion: 2017-04-01
• Study Completion: 2017-04-01
• Last Update Submitted: 2017-04-02
• Last Update Posted: 2017-04-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Freeman-Sheldon syndrome,
• Sheldon-Hall syndrome,
• Distal arthrogryposis type 1, or
• distal arthrogryposis type 3
• Deceased probands with enough clinical information available to satisfy study requirements
• Probands who participated in a prior Freeman-Sheldon Research Group (FSRG)-study are automatically accepted, since their diagnoses have been confirmed by FSRG clinical faculty.
• Probands with a reported qualifying diagnosis, who have not participated in a prior FSRG-study, will be required to complete the complete a survey from a prior study and provide photographs and any requested medical records to confirm their diagnoses.
• Family members and other close contacts may enrol, so long as they have either resided with or had substantial and prolonged contact with a proband, who has an FSRG-verified qualifying diagnosis. Investigators will make the final decision on a case-by-case basis, based on information provided.

Exclusion Criteria

• Patients with other anomalies, not having one of the above syndromes, will not be accepted.
• Deceased probands will not be accepted for analysis, without enough clinical data available to satisfy study data collection requirements.
• Patients or parents of minor children not willing to give consent will not be included.
• Family members or other contacts that neither resided with nor had substantial and prolonged contact with the proband.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Family Group	Center for Epidemiologic Studies Depression Scale	Persons who are genetically or legally related to a person with FSS or related condition
Proband Group	PTSD Checklist-Specific	Patients identified with FSS or a related condition
Proband Group	Modified Flanagan Quality of Life Scale	Patients identified with FSS or a related condition
Proband Group	Center for Epidemiologic Studies Depression Scale	Patients identified with FSS or a related condition
Proband Group	Functional Enquiry Form	Patients identified with FSS or a related condition
Proband Group	Strength, Joint ROM, Girth and Length Measurements	Patients identified with FSS or a related condition
Family Group	Functional Enquiry Form	Persons who are genetically or legally related to a person with FSS or related condition
Proband Group	Study Physical Examination	Patients identified with FSS or a related condition
Proband Group	Lactate, Glucose, and Adenosine Triphosphate Blood Levels	Patients identified with FSS or a related condition
Family Group	PTSD Checklist-Specific	Persons who are genetically or legally related to a person with FSS or related condition
Proband Group	PTSD, Depression, and FSS-Focused Examination	Patients identified with FSS or a related condition
Proband Group	Freeman-Sheldon Specific Quality of Life Survey	Patients identified with FSS or a related condition
Family Group	Freeman-Sheldon Specific Quality of Life Survey	Persons who are genetically or legally related to a person with FSS or related condition
Family Group	Lactate, Glucose, and Adenosine Triphosphate Blood Levels	Persons who are genetically or legally related to a person with FSS or related condition
Other Affected Individuals Group	PTSD Checklist-Specific	Persons who have had significant and meaningful contact with a person with FSS or related condition but do not qualify for family group enrolment
Other Affected Individuals Group	Strength, Joint ROM, Girth and Length Measurements	Persons who have had significant and meaningful contact with a person with FSS or related condition but do not qualify for family group enrolment
Other Affected Individuals Group	PTSD, Depression, and FSS-Focused Examination	Persons who have had significant and meaningful contact with a person with FSS or related condition but do not qualify for family group enrolment
Family Group	Modified Flanagan Quality of Life Scale	Persons who are genetically or legally related to a person with FSS or related condition
Family Group	Strength, Joint ROM, Girth and Length Measurements	Persons who are genetically or legally related to a person with FSS or related condition
Family Group	Study Physical Examination	Persons who are genetically or legally related to a person with FSS or related condition
Other Affected Individuals Group	Functional Enquiry Form	Persons who have had significant and meaningful contact with a person with FSS or related condition but do not qualify for family group enrolment
Other Affected Individuals Group	Study Physical Examination	Persons who have had significant and meaningful contact with a person with FSS or related condition but do not qualify for family group enrolment
Other Affected Individuals Group	Lactate, Glucose, and Adenosine Triphosphate Blood Levels	Persons who have had significant and meaningful contact with a person with FSS or related condition but do not qualify for family group enrolment
Family Group	PTSD, Depression, and FSS-Focused Examination	Persons who are genetically or legally related to a person with FSS or related condition
Other Affected Individuals Group	Modified Flanagan Quality of Life Scale	Persons who have had significant and meaningful contact with a person with FSS or related condition but do not qualify for family group enrolment
Other Affected Individuals Group	Center for Epidemiologic Studies Depression Scale	Persons who have had significant and meaningful contact with a person with FSS or related condition but do not qualify for family group enrolment
Other Affected Individuals Group	Freeman-Sheldon Specific Quality of Life Survey	Persons who have had significant and meaningful contact with a person with FSS or related condition but do not qualify for family group enrolment

Primary Outcome Measures

Name	Time	Method
Situational Mental Health in Persons with FSS or Related Condition	Evaluated during 1-2 study visits (lasting an average of 1-3 hours each) and in self-completed surveys, over an average of 2-4 years from enrolment	Increased frequency of mental health symptoms and diagnoses (PTSS, Depression, and reduced quality of life) over expected for general population

Secondary Outcome Measures

Name	Time	Method
Situational Mental Health in Family and Others with a Close Relationship to a Person with FSS or Related Condition	Evaluated during 1-2 study visits (lasting an average of 1-3 hours each) and in self-completed surveys, over an average of 2-4 years from enrolment	Increased frequency of mental health symptoms and diagnoses (PTSS, Depression, and reduced quality of life) over expected for general population
Current Survey Correlation with Disorder-Specific Survey for FSS and Related Conditions	Evaluated during 1-2 study visits (lasting an average of 1-3 hours each) and in self-completed surveys, over an average of 2-4 years from enrolment	Ability of current surveys to capture full picture of quality of life for persons, families, and others affected by FSS and related conditions will be assessed to determine need for a disorder-specific survey and usefulness of existing surveys.

Trial Locations

Locations (2)

Freeman-Sheldon Research Group, Inc. Headquarters; 🇺🇸 Buckhannon, West Virginia, United States

San Juan de Dios General Hospital; 🇬🇹 Guatemala City, Guatemala