Case of congenital ﬁbrosis of the extraocular muscles type 1
with progressive cerebellar ataxia
Toru Yamashita, Yoshiaki Takahashi, Keiichiro Tsunoda, Emi Nomura, Jingwei Shang,
Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta and Koji Abe
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
cerebellar ataxia, congenital ﬁbrosis of the
extraocular muscles type 1, KIF21A.
Accepted for publication 23 November 2017.
Koji Abe, Department of Neurology, Graduate
School of Medicine, Dentistry and
Pharmaceutical Sciences, Okayama
University, 2-5-1 Shikatacho, Okayama
A 70-year-old women presented classical CEFOM1 phenotypes such as bilateral
ptosis and external ophthalmoplegia, but also progressive cerebellar ataxia, carry-
ing a previously reported heterozygous missense mutation of KIF21A
p.Arg941Gln. The present case is the ﬁrst report of CFEOM1 showing cerebellar
atrophy with hypoperfusion, mainly of the vermis, indicating that cerebellar func-
tion should be carefully evaluated in CFFOM1 patients.
Congenital ﬁbrosis of the extraocular muscles (CFEOM) is a
hereditary eye disorder characterized by congenital eyelid
ptosis plus ophthalmoplegia.
CFEOM type 1 (CFEOM1) is
an autosomal dominant disorder that shows classical eyelid
ptosis as well as ophthalmoparesis and is caused by
heterozygous mutations in a kinesin gene, KIF21A.
Although typical CFEOM1 is not accompanied by any
other abnormalities, several reports showed CFEOM1
patients with a Marcus Gunn jaw-winking phenomenon.
Here, we report a CFEOM1 patient with classical CFEOM1
phenotypes plus progressive cerebellar ataxia, carrying a
previously reported heterozygous missense mutation of
The proband (patient III-5) is a 70-year-old (yo) Japanese house-
wife. She was born by natural delivery at full term, but was noted
also found in her grandmother, mother, aunt, and an older
brother (Fig. 1a). Her early development appeared normal.
When she visited a hospital at the age of 61, only bilateral ptosis
and ophthalmoplegia were pointed out to her. When she turned
68, she became aware of mild dysarthria, followed by gait distur-
When she visited our hospital at the age of 70, she
showed severe bilateral ptosis and both her eyes were ﬁxed
in a downward position (Fig. 1b). A neurological
examination revealed that extraocular movements were com-
pletely absent in all directions, but pupils were normal.
There was no evident muscle weakness or muscle atrophy in
all limbs, while she showed evident cerebellar ataxia with
dysarthria and truncal ataxia.
Motor and sensory nerve conduction studies showed nor-
mal amplitudes and velocities. Serum analysis was unre-
markable. A muscle biopsy of the left biceps brachii
revealed a minimal change (Fig. 1c) with a scattered moth-
eaten appearance following nicotinamide adenine dinu-
cleotide tetrazolium reductase (NADH-TR) staining
(Fig. 1d, arrows). Ragged-red ﬁbers were not found with
modiﬁed Gomori-trichrome staining (Fig. 1e). Magnetic res-
onance imaging demonstrated moderate cerebellar atrophy
(vermis dominant), without atrophy of the corpus callosum
or the brain stem (Fig. 1f–i, arrows). Cerebral blood ﬂow
showed hypoperfusion of cerebellar vermis (Fig. 1j–k,
For DNA analysis, written informed consent was
obtained from the patient and older (III-3) and younger
(III-6) sisters with approval of the research ethics committee
of Okayama University (#329). DNA of the patient and two
sisters underwent a genetic analysis by the Sanger method
for direct sequencing of KIF21A exon 8, 20, 21, and 22,
which were reported as hot spots for CFEOM1
, with the
following primers: 5
for exon 8, 5
for exon 20–21, and 5
Neurology and Clinical Neuroscience 6 (2018) 48–50
ª 2017 Japanese Society of Neurology and John Wiley & Sons Australia, Ltd