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What’s in a name? The clinical
features of facioscapulohumeral
muscular dystrophy
Karlien Mul, Saskia Lassche, Nicol C Voermans, George W Padberg,
Corinne GC Horlings, Baziel GM van Engelen
▸Additional material is
published online only. To view
please visit the journal online
(http://dx.doi.org/10.1136/
practneurol-2015-001353).
Department of Neurology,
Radboud University Medical
Center, Nijmegen,
The Netherlands
Correspondence to
Karlien Mul, Department of
Neurology, Radboud University
Medical Centre, P.O. Box 9101,
Nijmegen 6500 HB,
The Netherlands;
karlien.mul@radboudumc.nl
Accepted 5 January 2016
To cite: Mul K, Lassche S,
Voermans NC, et al.Pract
Neurol Published Online First:
[please include Day Month
Year] doi:10.1136/
practneurol-2015-001353
ABSTRACT
Facioscapulohumeral muscular dystrophy (FSHD)
is an inherited and progressive muscle disorder.
Although its name suggests otherwise, it
comprises weakness of the facial, shoulder and
upper arm muscles, and also of the trunk and
leg muscles. Its severity and disease course vary
greatly and mild or early FSHD can be difficult to
recognise. Knowledge of its subtle signs and
symptoms can lead directly to the correct
diagnosis without diagnostic delay and without
needing multiple diagnostic procedures. We give
an overview of the signs and symptoms of FSHD
in severe as well as in mild cases, to facilitate
correct and instant recognition of this relatively
common muscle disorder.
BACKGROUND
Facioscapulohumeral muscular dystrophy
(FSHD) is—despite being relatively
unknown to the general public and
perhaps to general neurologists as well—
the second most common autosomal
dominant muscular dystrophy in adults
(after myotonic dystrophy).
1
Most cases
are caused by a repeat contraction on
chromosome 4.
2
As its name suggests, it
affects muscles of the face, shoulder and
upper arm. However, many patients also
have weakness of the trunk and leg
muscles; sometimes these are even the
most pronounced symptoms. Moreover,
some patients have no or only very mild
symptoms. This large variability in pre-
senting symptoms and disease course can
hinder its recognition, especially in its
early stages.
The well-trained eye of a neurologist
familiar with the signs and symptoms can
frequently make the correct diagnosis of
FSHD at the first encounter. However,
the presentation can be subtle or easily
attributed to other conditions.
For example, facial weakness—the telltale
sign of FSHD—is often not recognised
by the patient and consequently may not
be explicitly reported. Additionally, facial
weakness can be very mild in up to 25%
of cases. As a result, we have seen
patients with FSHD present with a
myriad of symptoms that would not rou-
tinely trigger the search for an inherited
muscle disorder: unilateral foot drop,
shoulder complaints, frequent falling,
back pain and fatigue. Screening these
patients for the sometimes subtle other
clinical signs of FSHD can lead to a swift
diagnosis.
FSHD can be diagnosed by clinical
observation and by DNA testing, and so
its prompt recognition is important to
prevent diagnostic delay and unnecessary
(often invasive) diagnostic procedures. In
this paper, we review the signs and symp-
toms of FSHD in severe as well as in
mild cases, to facilitate the correct recog-
nition of all aspects of this relatively
common muscular dystrophy for the
‘non-trained’eye.
SYMPTOMS AND SIGNS
FSHD is traditionally described as a
slowly progressive muscular dystrophy
that manifests at age 15–30 years. It starts
with weakness of the facial and shoulder
girdle muscles, followed by the ankle dor-
siflexors and finally the proximal leg
muscles. However, many patients do not
fit this well-known classical FSHD
phenotype. Infantile and late-onset cases
are not uncommon and the severity and
sequence of involvement of different
muscle groups may vary.
The reported symptoms, therefore,
differ from patient to patient. Because of
the slow progression patients often do
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Mul K, et al.Pract Neurol 2016;0:1–7. doi:10.1136/practneurol-2015-001353 1
not (spontaneously) report all of their symptoms or
may attribute their symptoms to other more common
disorders, for example, to frozen shoulder or shoulder
tendon rupture. Additionally, although FSHD is an
autosomal dominantly inherited disorder, a negative
family history certainly does not rule it out. A high
percentage of cases, perhaps 10%–30%, are caused by
de novo mutations
34
and FSHD families frequently
include asymptomatic gene carriers.
5
Thus, FSHD is easily missed if a physician does not
actively ask for and look for its signs and symptoms.
Many patients with FSHD have multiple characteristic
signs (figure 1), some of which strongly suggest
FSHD, whereas other signs might more usually
accompany other neuromuscular and orthopaedic dis-
orders. Table 1 gives an overview of FSHD signs and
symptoms in each body region.
Face
Asymmetrical facial muscle weakness is one of the first
and most characteristic signs of FSHD (figure 2). The
most commonly affected facial muscles are the circular
muscles around the eyes (orbicularis oculi) and the
mouth (orbicularis oris) and the zygomaticus major.
Facial weakness can be very discreet in up to 25% of
cases and sometimes may be visible only as asymmetrical
pouting. Patients may be unaware of the facial muscle
involvement and physicians may not notice it in up to
60% of cases.
6
Patients rarely report facial weakness
symptoms spontaneously, and so physicians should pro-
actively ask about and look for it. For example, patients
(and relatives) might be asked if they have noticed a
change in facial expression. Some patients describe
being perceived as arrogant, grumpy or tired, through
their lack of facial expression. Orbicularis oculi weak-
ness gives difficulty in closing the eyelids and so many
patients sleep with their eyes partially open, and
develop irritated conjunctiva upon awakening. In more
advanced cases, a Bell’s phenomenon occurs on
attempting to close the eyes (figure 2A). Less pro-
nounced weakness can lead to a ‘signedecils’—an
inability to bury the eyelashes completely when attempt-
ing to close the eyes tightly (figure 2C).
Weakness of the orbicularis oris may lead to an asym-
metrical mouth in the resting position (figure 2B). This
becomes more visible when the patient attempts to
prude the lips or blow the cheeks (figure 2D).
Activities like whistling, blowing a balloon or drinking
through a straw can become more difficult. Some
patients lose mobility of the upper lip. Zygomaticus
muscle weakness causes an inability to raise the corners
of the mouth. On attempting to smile, the mouth
moves horizontally, producing a so-called ‘transverse
smile’, which may look like a grin. In severe cases,
other facial muscles can be involved as well, giving an
unwrinkled and expressionless ‘myopathic face’. The
extraocular muscles are never affected.
7
Upper limbs
In the upper limbs, there is often involvement of the
scapular fixator muscles, in particular the trapezius
and serratus anterior. This results in scapular winging,
which is often bilateral and frequently asymmetrical,
and which typifies FSHD (figure 3). Mild scapular
winging is not always visible at rest. The most sensi-
tive way to detect scapular winging is to observe the
scapula while the patient slowly lowers the arms for-
wards and/or sidewards.
8
Another important sign is
the ‘overriding scapula’, an upward movement of the
scapula due to loss of its inferior fixation. Scapular
instability together with muscle weakness causes diffi-
culty in abduction and forward flexion of the arms
above shoulder height. Patients complain first about
difficulty in working above shoulder height, then as
their symptoms progress, all activities requiring lifting
of the arms become more difficult, for example,
combing hair or removing a sweater.
Selective muscle wasting causes some characteristic
physical signs that may point to FSHD. So-called
‘Popeye’arms result from the contrast between the
atrophied perihumeral muscles, especially the biceps,
and the sparing (and subsequent normal bulk) of the
muscles of the forearms and relatively sparing of the
distal deltoid (figure 4). More severe cases may show
the ‘poly-hill’sign (figure 5),
9
resulting from selective
wasting of muscles. The first hill arises from atrophy
of the trapezius muscle combined with upward move-
ment of the superior angle of the scapula. More lat-
erally, the second hill arises through displacement of
the acromioclavicular joint. Next, the proximal
deltoid muscle is wasted while its distal part forms a
bulk (the third hill) and the biceps brachii again is
wasted. The supraspinatus and infraspinatus muscles
often appear fairly intact.
Trunk
Abdominal muscle weakness is an early and promin-
ent feature of FSHD, though often under-recognised.
Patients may have difficulty in rising from a supine to
a sitting position, for example, when getting out of
bed. As the weakness progresses, turning from one
side to the other when supine becomes more difficult.
On examination, the (asymmetrically) protruding
abdomen can be mistaken for abdominal fat instead of
muscle weakness. More specifically for FSHD, there
may be a positive Beevor’s sign: an upward movement
of the umbilicus on flexing the neck in the supine pos-
ition. Because the distal part of the rectus abdominis
muscle is weaker than the proximal part, the umbil-
icus gets pulled upwards (see figure 6 and online sup-
plementary video). Abdominal muscle weakness also
contributes to the lumbar hyperlordosis that most
patients have.
The other trunk muscles often affected are erector
spinae and pectoralis major. Erector spinae muscle
weakness can rarely cause ‘bent spine syndrome’
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2Mul K, et al.Pract Neurol 2016;0:1–7. doi:10.1136/practneurol-2015-001353
(camptocormia).
10
The combined weakness of abdom-
inal and back muscles is an important contributor to
patients’loss of balance and subsequent falling.
11
Atrophy of pectoralis major results in an, often asym-
metrical, extra anterior axillary fold (figure 7).
The respiratory muscles are not primarily involved
in FSHD. However, weakness of the trunk muscles,
including accessory respiratory muscles, and chest wall
deformities can give difficulty in breathing, but
patients rarely require ventilatory assistance.
12 13
Lower limbs
Although the disease is called FSHD, the vast majority
of patients also have weakness in the lower limbs. In
one observational study (122 patients), 20% presented
with lower limb weakness.
14
The sequence of
Figure 1 Characteristic signs of facioscapulohumeral muscular dystrophy.
Table 1 Signs and symptoms characteristic for FSHD
Body region
Specific symptoms in
history
Specific signs in
neurological examination
Most commonly
affected muscles
Red flags suggesting another
diagnosis
Face ▸Change in facial
expression
▸Difficulty in whistling
▸Sleeping with eyes
open
▸Bell’s phenomenon
▸Signe de cils
▸Asymmetrical pursing lips
or blowing cheeks
▸Transverse smile
▸Orbicularis oculi
▸Orbicularis oris
▸Weakness of extraocular muscles or
masseter
Upper limbs
and shoulders
▸Difficulty in working
above shoulder
height
▸Shoulder pain
▸Asymmetrical winging of
scapula and over-riding
scapula
▸Poly-hill sign
▸‘Popeye’arms
▸Trapezius
▸Serratus anterior
▸Distal part of deltoid
▸Triceps and biceps
brachii
▸Weakness of brachioradialis and/or distal
arm and hand muscles in early stage
disease
Trunk ▸Difficulty in moving
from supine to
sitting position
▸Loss of balance
▸Horizontal axillary fold,
often asymmetrical
▸Beevor’s sign
▸Horizontal clavicles
▸Prominent abdomen with
hyperlordosis
▸Pectoralis major
(sternal part more
than clavicular part)
▸Erector spinae
▸Rectus abdominis
▸Weakness of sternocleidomastoid
▸Early respiratory muscle weakness
Lower
extremity
▸Tripping, falling
▸Difficulty in walking
up stairs or rising
from a chair
▸Dropped foot
▸Trendelenburg’s sign
▸Adductor magnus
▸Hamstrings
▸Quadriceps femoris
▸Tibialis anterior
▸Profound weakness of iliopsoas or
gastrocnemius in the absence of other
leg muscle weakness
FSHD, facioscapulohumeral muscular dystrophy.
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Mul K, et al.Pract Neurol 2016;0:1–7. doi:10.1136/practneurol-2015-001353 3
involvement of the leg muscles differs between
patients. A classical feature of FSHD is weakness of
the tibialis anterior muscle, eventually causing foot
drop. Foot drop is prevented for a long time by hyper-
trophy of the extensor digitorum brevis, often cited as
a feature distinguishing the myopathy from a
neuropathy.
Hamstrings weakness is very common but usually
does cause functional limitations to daily life. The calf
and quadriceps muscles may also be affected (figure 8).
Trendelenburg’s sign is not specific for FSHD, but is
frequently develops the advanced cases when walking
becomes difficult.
Pain and fatigue
Approximately 75% of patients with FSHD experi-
ence moderately severe chronic pain, mostly in the
lower back, legs, shoulder region and neck.
15 16
Around 60% experience severe fatigue,
17
related to
multiple perpetuating factors including pain, sleep dis-
turbance, physical activity and impairment.
18
Systemic involvement
Cardiac involvement includes an increased prevalence
of (incomplete) right bundle branch block, though
without cardiac symptoms or progression to clinically
relevant cardiac arrhythmias.
19
FSHD does not cause
cardiomyopathy; finding this should prompt suspicion
of other disorders.
Retinal vasculopathy is associated with FSHD. It is
mostly subclinical but can, mostly in severely affected
early onset cases with very short repeat sizes, progress
to Coat’s syndrome.
20
Coat’s syndrome is a treatable
condition, characterised by retinal vascular abnormal-
ities and leakage that can cause exudative retinal
detachment and blindness. High-frequency hearing
loss may occur in patients with FSHD but appears
mostly to be subclinical. Patients with early onset
severe disease may develop hearing loss requiring
hearing aids. Pectus excavatum occurs in 5%–16% of
patients with FSHD and occasionally may be severe.
21
There are a few case reports describing mental retard-
ation and/or epilepsy in patients with severe FSHD.
DIAGNOSTIC INVESTIGATIONS
The history and physical examination are the key-
stones to the diagnosis; direct DNA testing can
confirm it if there is a high clinical suspicion. Muscle
biopsy and laboratory tests are not sufficiently specific
to make the diagnosis of FSHD. The serum creatine
Figure 2 Weakness of the orbicularis oculi results in difficulty or inability in closing both eyes (A) and a ‘signe de cils’(C).
(B) The mouth is asymmetrical in its resting position. (D) Orbicularis oris weakness causes difficulty in pursing the lips (D).
Figure 3 Asymmetrical bilateral scapular winging (right more
than left) becoming visible on forward lowering of the arms.
Figure 4 Horizontal axillary folds, protuberant abdomen and
over-riding scapula. Also note the distal wasting of the deltoid
muscle with an intact proximal part and the wasting of the
humeral muscles with a normal bulk of the muscles of the
forearm.
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4Mul K, et al.Pract Neurol 2016;0:1–7. doi:10.1136/practneurol-2015-001353
kinase concentration is either normal or slightly ele-
vated (but never more than five times of normal).
FSHD1 can be diagnosed genetically by assessing the
size of the repeat contraction on chromosome 4; finding
≤10 repeat units on a 4qA allele is consistent with the
diagnosis. FSHD1 is the most common type (95%) of
FSHD. Repeat size is reported as EcoRI band, in which
fragments ≤38 kb are consistent with FSHD1. The
reported EcoRI/BlnI band is used only to confirm that
the repeat contraction is located on chromosome 4 and
not on a similar repeat array on chromosome 10. In case
of a repeat contraction on chromosome 4, the EcoRI/
BlnI band is 3 kb shorter than the EcoRI band. Because
FSHD1 is caused by a repeat contraction, current high
yield genetic sequencing such as exome sequencing tech-
niques fail to detect FSHD1.
In case of a negative test (fragment size >38 kb)
and a high clinical suspicion for FSHD, it is worth
testing for FSHD2. This accounts for 5% of patients
who have heterozygous mutations in the SMCHD1
gene, and has a clinical phenotype indistinguishable
Figure 5 Poly-hill sign (from the back). Arrow 1: wasting of
trapezius, arrow 2: superior angle of the scapula, arrow 3:
displaced of the acromioclavicular joint, arrow 4: atrophied
proximal deltoid and arrow 5: normal bulk of distal deltoid.
Figure 6 (Online supplementary video). Beevor’s sign: upward
movement of the umbilicus on flexing the neck in supine
position, due to more pronounced weakness of the distal part
of the rectus abdominis than the proximal part.
Figure 7 A horizontal anterior axillary fold visible on both
sides of the trunk. The abdomen protrudes asymmetrically.
Figure 8 Atrophy of the right calf muscles.
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Mul K, et al.Pract Neurol 2016;0:1–7. doi:10.1136/practneurol-2015-001353 5
from FSHD1.
22
There are reports of patients with
very severe FSHD who carry mutations for FSHD1 as
well as for FSHD2.
23
A small number of patients with
an FSHD phenotype have negative tests for both
FSHD1 and FSHD2 and cannot be explained genetic-
ally at this moment. In case of negative genetic testing
for FSDH1 and/or FSHD2, other diagnoses should be
considered.
24
A more detailed description of genetic
testing lies beyond the scope of this paper and can be
found elsewhere.
25 26
COUNSELLING AND MANAGEMENT
FSHD is an autosomal dominantly inherited disorder.
The muscle weakness is typically slowly progressive,
although the disease severity varies greatly between
and within families. When compared with other mus-
cular dystrophies, FSHD may have a more stepwise
disease progression, sometimes with years of stabilisa-
tion of progression, followed by a period with rela-
tively fast progression of muscle weakness. Therefore,
it is not possible at present to predict an individual
disease course. One in five patients with FSHD
becomes wheelchair dependent by the age of
50 years.
27
Factors associated with a more severe
phenotype are the early onset of symptoms and very
short repeat sizes (10–20 kb).
28
Life expectancy is
generally not reduced.
29
Patients should be referred
for genetic counselling for information regarding
recurrence risk. Preimplantation genetic diagnosis is
technically very difficult for FSHD, because of the
large amount of DNA that is required to perform the
Southern blot analysis. In large families, it is possible
to use proximal flanking markers, but this technique
has a 5% chance of false result because the FSHD
repeat lies distally on chromosome 4q and because
this area has a high recombination frequency.
There is currently no cure or medicinal treatment
available for FSHD. Treatment is focused on improv-
ing functional limitations and maintaining an optimal
physical condition. Therefore, all patients with func-
tional limitations should have a rehabilitation consult-
ation.
24
Several studies have focused on treating the
symptoms of physical limitations and fatigue. Aerobic
exercise can help chronic fatigue, physical activity and
fitness.
30 31
Cognitive behavioural therapy can also
help chronic fatigue through tackling fatigue-
perpetuating factors.
30
There is a recently developed evidence-based guide-
line for managing and screening for complications of
FSHD.
28
This advises obtaining baseline pulmonary
function tests on all patients with FSHD, especially
those severely affected (wheelchair users and/or with
chest wall deformities). It is not necessary to under-
take routine cardiac screening. Also, routine assess-
ment for retinal vasculopathy and hearing loss is not
necessary, except in severe infantile cases (using
dilated indirect ophthalmoscopy and screening audi-
ometry). All patients with FSHD undergoing elective
surgery need preoperative screening, to include an
assessment of respiratory function.
CONCLUSION
FSHD is an inherited progressive muscle disorders
that—despite its name—comprises more than just
weakness of the facial, scapular and humeral muscles.
An awareness of the signs and symptoms of FSHD,
which may be subtle, allows prompt diagnosis, and
hence reduced diagnostic delay and avoidance of
(often invasive) diagnostic procedures. The diagnosis
can be confirmed genetically. Treatment is currently
aimed at improving functional limitations.
Key points
▸The muscle weakness in facioscapulohumeral muscu-
lar dystrophy (FSHD) includes the facial and shoulder
girdle muscles, and also the trunk and the legs.
▸Patients often do not recognise the typical signs,
which emphasises the importance of the neurological
examination in these patients.
▸Familiarity with its variability and subtleness of signs
and symptoms allows the physician to diagnose
FSHD at the first clinical encounter and to confirm it
by genetic testing.
Contributors KM, SL and CGCH formulated the article,
drafted the manuscript and revised it. KM and GWP
contributed the figures. NCV, GWP and BGMvE revised the
manuscript. All authors approved the final version of the
manuscript.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Commissioned; externally peer
reviewed. This paper was reviewed by Nick Davies,
Birmingham, UK.
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