Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome

This study was initiated by the research assistant (Mikaela I. Poling) and assisted by
another research assistant (J. Andrés Morales), as part of their academic project on these
syndromes, under the supervision of the Principal Investigator (Robert L Chamberlain).

Classic FSS, SHS, DA1, and DA3 are poorly understood pathological entities that share some
similar physical findings to FSS. Stevenson et al. (2006) provided the only study to date on
FSS features and history. They did not, however, focus on therapeutic outcomes, and there was
limited anecdotal outcome data in single and multiple case reports.

The objectives for STOP-FSS are as follows: to evaluate (1) physical findings, possible
frequency clusters, and complications of physical findings amongst patients with FSS; (2)
posttraumatic stress and depressive symptoms and associated therapeutic outcomes in patients
with FSS, using single-disease specific (i.e., posttraumatic stress symptoms, chronic
depression) measures; (3) document treatment types and outcomes; (4) evaluate quality of life
in patients with FSS, using a general quality of life self-report measure and
syndrome-specific semi-structured quality of life interview; (5) educational attainment and
services used; (6) evaluate diagnostic accuracy of FSS and SHS, using the Stevenson criteria;
and (7) evaluate possible differences with patients meeting the full Stevenson criteria and
those fulfilling the craniofacial part of the Stevenson criteria, with or without additional
malformations.

The following hypotheses are thus proposed. First, it is suggested that physical findings and
frequency clusters will be similar to those previously reported, but complications of
physical findings amongst patients with FSS, having received little attention in the
literature, will be pronounced and result in nearly as significant of a disease burden for
the patient as the primary physical findings themselves, e.g., intercostal myopathy
eventually leading to right heart failure in some patients. Second, it is suggested that FSS
is associated with higher rates of posttraumatic stress symptoms, depressive symptoms than is
observed in the general population. Third, it is suggested that physiotherapy alone or with
surgery is expected to be superior to surgery alone, especially for patients with FSS, in
treating most problems, but surgery may have an important role, especially treating
blepharophimosis and in combination with intensive pre- and post-operative physiotherapy in
treating selective tendon lengthening in hands and feet. Fourth, it is suggested that FSS is
associated with reduced quality of life than is observed in the general population. Fifth, it
is suggested that when patients with FSS who do not have neurocognitive features receive the
appropriate academic services, they frequently excel beyond family and peers, and it is also
suggested that most patients with FSS do not receive educational services that are responsive
to their unique needs and abilities, e.g., placement in 'special' classes or schools based on
the patient's appearance or poorly conducted intelligence tests. Sixth, it is suggested,
based on systematic review and meta-analysis preliminary results, that two-thirds of patients
with a stated diagnosis of FSS will not meet the Stevenson criteria and be rediagnosed,
mostly as DA1. Seventh, it is suggested, based on systematic review and meta-analysis
preliminary results, that two-thirds of patients with stated diagnosis of FSS who do not meet
the Stevenson criteria, one-third will be meet the craniofacial stipulates of the Stevenson
criteria, with or without additional malformations, and share a natural history with those
who met the full Stevenson criteria.

Inclusion Criteria:

- Patients who have phenotypes consistent with (1) the Stevenson criteria for classic
FBS or SHS; (2) one of four tentative FBS subtypes; or (3) DA1A, DA1B, or DA3.

- Any of the following: (1) patients or parents of minor children willing to give
consent, or (2) patients who are deceased or (3) retrospective chart review patients
(living or deceased) who have enough clinical data available to establish the
diagnosis and satisfy minimum data collection requirements.

- Persons who speak English, Spanish, German, Russian, or Czech.

Exclusion Criteria:

- Patients who do not have phenotypes consistent with (1) the Stevenson criteria for
classic FBS or SHS; (2) one of four tentative FBS subtypes; or (3) DA1A, DA1B, or DA3.

- Any of the following: (1) patients or parents of minor children not willing to give
consent, or (2) patients who are deceased or (3) retrospective chart review patients
(living or deceased) who do not have enough clinical data available to establish the
diagnosis and satisfy minimum data collection requirements.

- Potentially persons who speak languages other than English, Spanish, German, Russian,
or Czech, subject to translator availability