Satoyoshi Syndrome With Unusual SkeletalAbnormalities and Parental ConsanguinityC.A. Venegas-Vega,1* M.R. Rivera-Vega,1 S. Cuevas-Covarrubias,1 J. Orozco,2 and S. Kofman-Alfaro1
1Department of Human Genetics, Facultad de Medicina, Hospital General de Mexico, UNAM, Mexico City, Mexico2Department of Neurology, Hospital General de Mexico, Mexico City, Mexico
Received 19 March 2008; Accepted 2 January 2009
Satoyoshi syndrome (SS) (OMIM 600705) is a rare multisystemic
disorder of unknown etiology characterized by progressive pain-
ful intermittent muscle spasm, alopecia universalis, diarrhea,
short stature, amenorrhea, and secondary skeletal abnormalities
mimicking a metaphyseal chondrodysplasia. To date all reported
cases have been sporadic. We describe a 26-year-old Mexican
woman, a product of consanguineous parents with clinical
characteristics of SS. Our patient, also showed skeletal
anomalies not previously reported that seems to be a coincidental
finding. 2009 Wiley-Liss, Inc.
Key words: Satoyoshi syndrome; muscle spasm; alopecia; amen-orrhea; short stature; skeletal abnormalities; parental consanguinity
Satoyoshi syndrome (SS) (OMIM 600705) is a rare disorder of
unknown etiology. Progressive painful intermittent muscle spasm,
alopecia universalis, and diarrhea are the three cardinal symptoms.
Other clinical findings include, short stature, skeletal anomalies,
and amenorrhea [Satoyoshi and Yamada, 1967; Satoyoshi, 1978;
Ehlayel and Lacassie, 1995; Ikeda et al., 1998]. To date approxi-
mately 50 cases have been reported in different ethnic groups
[Merello et al., 1994; Ehlayel and Lacassie, 1995; Cecchin et al.,
2003; Ashalatha et al., 2004]. SS is a sporadic condition more
common in women than in men. Although several reports
have proposed an autoimmune mechanism, the pathogenesis of
SS remains unknown [Satoh et al., 1983; Yamagata et al., 1991]. In
this article, we describe the first Mexican patient with clinical data of
SS and several skeletal alterations and parental consanguinity not
The patient was a 26-year-old Mexican female referred to the
Genetic Department of the General Hospital of Mexico by alopecia,
short stature, muscle spasm, and amenorrhea. She was the product
of healthy, young, and consanguineous parents (Fig. 1). Family
history of the disorder was negative. Her growth, development, and
behavior were normal until 6 years of age, when she presented hair
loss on the scalp, eyebrows and eyelashes, and delayed growth. One
year later she began with recurrent painful cramps in feet and calves.
Menarche began at age 12 with oligomenorrhea, and at 16 years old
presented amenorrhea. On clinical examination at age of 26 years,
she is an intelligent woman with height 120 cm (centile
cramps (two or three each year) with no other additional
SS (OMIM 600705) is a disorder with multisystem involvements
[Satoyoshi, 1978; Ehlayel and Lacassie, 1995]. Patients with SS are
normal at birth and the characteristic phenotype usually appears
later [Ehlayel and Lacassie, 1995]. The typical age of onset is before
15 years old; however, three adult onset cases have been reported
[Merello et al., 1994; Tajima et al., 1994; Ikeda et al., 1998].
Muscle spasm is the initial symptom in nearly all cases and
usually starts between the ages of 4 and 19 years [Satoyoshi, 1978;
Satoh et al., 1983; Ikegawa et al., 1993a]. It was proposed that spasms
could be consequence of hyperactivity or a disinhibition at the alpha
motor neuron level [Satoyoshi, 1978; Merello et al., 1994; Drost
et al., 2006]. Alopecia universalis usually starts between the ages of
6 and 21 years [Satoyoshi, 1978; Satoh et al., 1983; Wisuthsarewong
et al., 2001]. Our patient had hair loss before spasms and muscle
hypertrophy as has been observed [Satoyoshi, 1978; Kuru et al.,
1992; Tajima et al., 1994; Ehlayel and Lacassie, 1995; Wisuthsar-
ewong et al., 2001; Cecchin et al., 2003]. Laboratory results were
similar to those previously described [Satoyoshi, 1978; Yamagata
et al., 1991; Ikegawa et al., 1993a; Ehlayel and Lacassie, 1995;
Ikeda et al., 1998; Wisuthsarewong et al., 2001; Endo et al., 2003;
Kamat et al., 2003].
The most striking skeletal-radiological findings include slipping
of multiple epiphyses, cystic lesions of metaphyses, acro-osteolysis,
early osteoarthrosis, bone fragmentation at tendinous insertions,
fatigue fractures, and residual joint deformity [Matsuo et al., 1983;
Satoh et al., 1983; Ikegawa et al., 1993a,b; Haymon et al., 1997].
However, in our patient an extensive radiology evaluation ruled out
these alterations. Other orthopedic features, frequent in SS, such as
genu valgus and pes planus [Satoyoshi, 1978], were also observed.
Satoyoshi  reported a correlation between the severity of the
spasms and the skeletal changes and deformities. When cramps
begin before age 12, mild growth retardation and joint deformities
are the most striking features [Satoyoshi, 1978; Ikegawa et al.,
1993b]. In our case onset of cramps was at 7 years, conversely to
previous reports our patient presented severe short stature, and the
distributions of bone malformations did not correspond to spasms.
Although several differential diagnoses exist with these skeletal
alterations; such as cartilage-hair hypoplasia syndrome (OMIM
250250), spondyloepimetaphyseal dysplasia with hypotrichosis
(OMIM 183849), and brachydactyly-mental retardation syndrome
(OMIM 600430); the clinical, laboratory, and radiological findings
in our patient ruled out these conditions. However, based on the
radiological findings, it is not possible to establish a specific
diagnosis. We also consider that skeletal symptoms are completely
unrelated to the SS, and that the co-occurrence is just coincidence.
The association with different autoimmune disorders or immu-
nological alterations [Satoyoshi, 1978; Satoh et al., 1983; Yamagata
et al., 1991] and the response of some symptoms to glucorticoids
treatment [Yamagata et al., 1991; Kuru et al., 1992; Ehlayel and
Lacassie, 1995; Oyama et al., 1999] suggests that the autoimmunity
plays an important role in the pathogenesis of SS. Nevertheless,
there is no direct evidence to support an autoimmune hypothesis
[Ikeda et al., 1998]. Although all cases have been sporadic, in our
case parental consanguinity could suggest an autosomal recessive
pattern; however, this could be only a co-incidental finding. In
conclusion, we reported the first Mexican patient with SS. Consid-
ered careful long-term follow-up of the radiological and orthopedic
features is mandatory in these patients. Additional reports are
required in order to define the full phenotype spectrum and genetic
basis of this condition.
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