Clinical trial NCT01307475: Study of Quality of Life in Freeman-Sheldon Syndrome and Related Conditions
Official title: Freeman-Sheldon Syndrome Quality of Life Study (FSS-QLS): Cross-sectional Study of Concomitant Disorder-Specific Contributors to Quality of Life and Clinical Outcome
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Arthrogryposis
Craniofacial Abnormalities
Posttraumatic Stress Disorder
Depressive Disorder
Keywords: Chronic Post-Traumatic Stress Disorder
Delayed Onset Post-Traumatic Stress Disorder
Post-Traumatic Neuroses
Posttraumatic Neuroses
Post-Traumatic Stress Disorders
Posttraumatic Stress Disorders
PTSD
Post TraumaticStress Disorder
Endogenous Depression
Neurotic Depression
Depressive Syndrome
Melancholia
Depressive Neurosis
Unipolar Depression
Depressive Symptoms
Emotional Depression
Quality of Life
Lead sponsor: Freeman-Sheldon Research Group, Inc.
Sponsor class: OTHER
First posted: 2011-03-03
Enrollment: 6
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients, family, and others affected world-wide are welcome, so long as they currently or previously have had significant and meaningful contact with a person who has a qualifying diagnosis.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Situational Mental Health in Persons with FSS or Related Condition
timeFrame: 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
Secondary outcomes:
measure: Situational Mental Health in Family and Others with a Close Relationship to a Person with FSS or Related Condition
timeFrame: 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
measure: Current Survey Correlation with Disorder-Specific Survey for FSS and Related Conditions
timeFrame: 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
Other outcomes:
Locations:
city: Buckhannon
country: United States
facility: Freeman-Sheldon Research Group, Inc. Headquarters
state: West Virginia
city: Guatemala City
country: Guatemala
facility: San Juan de Dios General Hospital
Study officials:
affiliation: Freeman-Sheldon Research Group, Inc.
name: Robert L Chamberlain, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Apajasalo M, Sintonen H, Rautonen J, Kaitila I. Health-related quality of life of patients with genetic skeletal dysplasias. Eur J Pediatr. 1998 Feb;157(2):114-21. doi: 10.1007/s004310050781.
citation: Didierjean-Pillet A. [Psychological approach to congenital hand deformities. Congenital deformities, the desire to know]. Ann Chir Plast Esthet. 2002 Feb;47(1):2-8. doi: 10.1016/s0294-1260(01)00079-6. French.
citation: Nagata S, Funakosi S, Amae S, Yoshida S, Ambo H, Kudo A, Yokota A, Ueno T, Matsuoka H, Hayashi Y. Posttraumatic stress disorder in mothers of children who have undergone surgery for congenital disease at a pediatric surgery department. J Pediatr Surg. 2008 Aug;43(8):1480-6. doi: 10.1016/j.jpedsurg.2007.12.055.
citation: Vitale MG, Choe JC, Vitale MA, Lee FY, Hyman JE, Roye DP Jr. Patient-based outcomes following clubfoot surgery: a 16-year follow-up study. J Pediatr Orthop. 2005 Jul-Aug;25(4):533-8. doi: 10.1097/01.bpo.0000157999.38424.ba.
citation: Roye BD, Vitale MG, Gelijns AC, Roye DP Jr. Patient-based outcomes after clubfoot surgery. J Pediatr Orthop. 2001 Jan-Feb;21(1):42-9. doi: 10.1097/00004694-200101000-00010.
citation: Vitale MG, Levy DE, Johnson MG, Gelijns AC, Moskowitz AJ, Roye BP, Verdisco L, Roye DP Jr. Assessment of quality of life in adolescent patients with orthopaedic problems: are adult measures appropriate? J Pediatr Orthop. 2001 Sep-Oct;21(5):622-8.
citation: Hawkins SS, Radcliffe J. Current measures of PTSD for children and adolescents. J Pediatr Psychol. 2006 May;31(4):420-30. doi: 10.1093/jpepsy/jsj039. Epub 2005 Jun 9.
citation: McCormick RJ, Poling MI, Portillo AL, Chamberlain RL. Preliminary experience with delayed non-operative therapy of multiple hand and wrist contractures in a woman with Freeman-Sheldon syndrome, at ages 24 and 28 years. BMJ Case Rep. 2015 Jul 14;2015:bcr2015210935. doi: 10.1136/bcr-2015-210935.
citation: McCormick RJ, Poling MI, Chamberlain RL. Bilateral patellar tendon-bearing Symes-type prostheses in a severe case of Freeman-Sheldon syndrome in a 21-year-old woman presenting with uncorrectable equinovarus. BMJ Case Rep. 2015 Jul 15;2015:bcr2015211338. doi: 10.1136/bcr-2015-211338.
citation: Chamberlain RL, Poling MI, Portillo AL, Morales A, Ramirez RR, McCormick RJ. Freeman-Sheldon syndrome in a 29-year-old woman presenting with rare and previously undescribed features. BMJ Case Rep. 2015 Oct 22;2015:bcr2015212607. doi: 10.1136/bcr-2015-212607.
citation: Poling MI, Dufresne CR, Chamberlain RL. Dr Ben Franklin and an unusual modern-day cure for recurrent pleuritis. Br J Gen Pract. 2017 Jan;67(654):32-33. doi: 10.3399/bjgp17X688705. No abstract available.
citation: Poling MI, Morales Corado JA, Chamberlain RL. Findings, phenotypes, and outcomes in Freeman-Sheldon and Sheldon-Hall syndromes and distal arthrogryposis types 1 and 3: protocol for systematic review and patient-level data meta-analysis. Syst Rev. 2017 Mar 6;6(1):46. doi: 10.1186/s13643-017-0444-4.