CLINICAL REPORT

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 M�exico, UNAM, M�exico City, Mexico2Department of Neurology, Hospital General de M�exico, M�exico 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

INTRODUCTION

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

previously reported.

CLINICAL REPORT

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<3), weight

28 kg (centile <3), OFC 47 cm (centile <3), fine sparse hair in

the scalp, no visible eyebrows and eyelashes, beaked nose with

columnela below alae nasi, narrow maxilla and prognathism

(Fig. 2A), mild atrophic subcutaneous tissues, underdeveloped

mammary glands, and no axillary or pubic hair. The muscles of

the upper and mainly lower limbs were hypertrophic, with normal

strength. Mild genu valgus and lumbar scoliosis were also present.

Stubby hands and feet with short fingers and toes, clinodactily,

broad thumbs, mild hallux valgus, and pes planus were observed

(Fig. 2B). No diarrhea or loose stools were mentioned.

Complete blood count, erythrocyte sedimentation rate, urinal-

ysis, serum electrolytes, alkaline phosphatase, aldolase, glucose,

urea, BUN, and creatinine were with normal limits. Serum creati-

nine phosphokinase (CPK) and uric acid were mildly elevated at

245 IU/L and 8.30 mg/dl, respectively (normal ranges: 24–235 IU/L

and 2.4–7.0 mg/dl). Serum IgG, IgA, and IgM, and lymphocyte

subpopulations were also normal. Serum IgE was highly elevated,

at 1,960 IU/ml (normal <158 IU/ml). Test results for anti-DNA,

*Correspondence to:

C.A. Venegas-Vega, Department of Genetics, Facultad de Medicina,

Hospital General de M�exico, UNAM, Dr. Balmis 148, Col. Doctores, CP

06726, Mexico City, Mexico. E-mail: cavene@yahoo.com

Published online 16 October 2009 in Wiley InterScience

(www.interscience.wiley.com)

DOI 10.1002/ajmg.a.32751

How to Cite this Article:Venegas-Vega CA, Rivera-Vega MR, Cuevas-

Covarrubias S, Orozco J, Kofman-Alfaro S.

2009. Satoyoshi syndrome with unusual

skeletal abnormalities and parental

consanguinity.

Am J Med Genet Part A 149A:2448–2451.

� 2009 Wiley-Liss, Inc. 2448

anti-GAD, rheumatoid factor, VDRL, and thyroid antibody were

negative. Antinuclear antibody was positive at 1:100 with speckled

pattern. No cytogenetic abnormalities were observed in the prom-

etaphase chromosomal study. Electromyographic studies demon-

strated large action potential and nerve conduction velocity showed

possible mix injury of sensitive-motor type.

X-rays disclose brachymetacarpism with ‘‘mushroom ap-

pearance,’’ short phalanges with moderate apical narrowing, short

metatarsals with ‘‘mushroom’’ appearance and apical narrowing.

Iliac wings and mild genu valgus (Fig. 2C). No spine anomalies,

fractures, cystic lesions, or slippage of the epiphyses were

observed. Pelvic ultrasound showed hypoplastic uterus and ovaries.

At age of 21 she started on a combination of tetrazepam 50 mg

and carbamazepine 300 mg per day. After 1 month of management,

she showed a diminution in the severity and frequency of the

spasms. Between 21 and 26 years old, she had few episodes of the

FIG. 2. A: Frontal and occipital views of patient demonstrating facial appearance and baldness. B: Proportionate short stature and hypertrophic

muscles of lower limbs are noted. C: X-ray hand and feet. Observed, shortness of all metacarpals (more severe third and fourth), metatarsals, and

phalanges (principally, in the first telephalanges). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

FIG. 1. Family pedigree.

VENEGAS-VEGA ET AL. 2449

cramps (two or three each year) with no other additional

symptoms.

DISCUSSION

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 [1978] 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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