A natural history study on infantile facioscapulohumeral muscular dystrophy: five-year follow-up

Fascioscapulohumeral dystrophy (FSHD) is one of the most common hereditary
muscular diseases and typically causes progressive, asymmetric atrophy and
weakness of the facial, scapulohumeral, tibial and axial muscles. The FSHD
phenotype encompasses a broad spectrum of severity ranging from non-penetrant
mutation carriers to severely affected patients.

Type 1 FSHD, responsible for over 95% of the FSHD cases, is associated with a
contraction of the D4Z4-repeat on chromosome 4q45. It was believed that fewer
D4Z4 repeats correlated with more severe disease, but research showed this
relation to be inconsistent.
The age of symptom onset in FSHD is variable, in approximately one fifth of all
the patients FSHD starts in childhood. FSHD in childhood is associated with a
fewer number of D4Z4-repeats, more extensive muscle weakness and more systemic
features (e.g. epilepsy, hearing deficits, Coats disease, mental retardation
and cardiac arrhythmia) compared to those of similar age and disease onset with
a 'classic onset FSHD'.


Our baseline study on childhood FSHD in the Netherlands showed that this
subgroup is less affected than previously thought. The full spectrum of FSHD in
childhood is much broader and characterized by a significant variability in
symptoms and clinical course. Our follow-up study showed mild progression over
two years of follow-up. Extra-muscular symptoms such as hearing loss appeared
less prevalent in the infantile subgroup than suggested in literature. The
studies also identified pain, fatigue and decreased quality of life as major
problems among children with FSHD.


In conclusion, FSHD in childhood appears to be a slowly progressive disease.
Since data on the natural history, prognostic markers and clinical management
of FSHD in childhood is still limited, a longer follow-up period is expected to
provide further information about the natural history. Obtaining this knowledge
is critical for optimal patient care and counseling. Furthermore, this
knowledge is expected to support longer running treatment trials. Our proposed
study will further contribute to reachting clinical trial readiness in
childhood FSHD.

The primary objective of this study is to further discribe the natural course
and clinical characteristic of infantile FSHD.

The secondary objectives are:
- To identify (epi)genetic and environmental disease modifying factors that
contribute to variances in the clinical phenotype of FSHD.
- To Identify the main problems faced by children with FSHD in order to
improve rehabilitation in the future.
- To identify or validate biomarkers and modulators of disease severity
- To obtain and documentate the natural history of FSHD in a cohort of
children, in preparation for possible future clinical trials.To this end we
will inform subjects of the existence of the FSHD registration website
(www.fshdregistratie.nl).

This study is a prospective, observational study.

The burden on the study consists of a single hospital visit (expected duration
of 4 hours) for a number of examinations. These are all non-invasive and
non-painful studies, so the risk in this study is very low.