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Satoyoshi syndrome: An unusual postnatal multisystemic disorder

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  • American Journal of Medical Genetics 57:620-625 (1995)

    Satoyoshi Syndrome: An Unusual Postnatal Multisystemic Disorder

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    Mohammad S. Ehlayel and Yves Lacassie Department of Pediatrics (M.S.E., Y.L.) and Center for Molecular and Human Genetics (Y.L.), Louisiana State University Medical Center, and Childrens Hospital (Y.L.), New Orleans, Louisiana

    Satoyoshi syndrome is a rare disorder of un- known cause characterized by progressive, painful intermittent muscle spasms, malab- sorption, alopecia, amenorrhea, and skele- tal abnormalities mimicking a skeletal dys- plasia. We describe a 19-year-old Caucasian woman with characteristic manifestations starting at age 9. The report of this patient confirms that this condition is not limited to the Asian population.

    KEY WORDS: Satoyoshi syndrome, muscle spasm, alopecia, amenor- rhea, malabsorption, skeletal abnormalities, Caucasian

    1995 Wiley-Liss, Inc.

    INTRODUCTION Satoyoshi syndrome is a rare disorder of unknown

    cause characterized by progressive, painful, intermit- tent muscle spasms, diarrhea or unusual malabsorp- tion, endocrinopathy with amenorrhea, and secondary skeletal abnormalities [Satoyoshi and Yamada, 1967; Satoyoshi, 1978; Ikegawa et al., 1993a,b; Yamagata et al., 19911. Since the first report by Satoyoshi and Yamada [1967] on 2 cases with recurrent spasms, about 27 cases have been reported [Ikegawa et al., 199313; Merello et al., 1994; Averianov et al., 19841. Surpris- ingly, most of them have been reported in Japan. All but 3 patients have been Asian: case 10 in a review of 15 cases [Satoyoshi, 19781 from the United Kmgdom (but no ethnic information was available as the patient was adopted), a Russian patient [Averianov et al., 19841, and an Amerindian male from Argentina [Merello et al., 19941. To the best of our knowledge, our patient is the first Caucasian case ever reported in the

    Received for publication September 26, 1994; revision received January 27,1995.

    Address reprint requests to Yves Lacassie, M.D., Division of Genetics, Department of Pediatrics, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, LA 70112-2822.

    0 1995 Wiley-Liss, Inc.

    United States, and probably in the world, confirming that this condition is not limited to the Japanese or Chinese populations [Merello e t al., 19941.

    CLINICAL REPORT A 19YL-year-old Caucasian woman was admitted for

    diagnostic evaluation of amenorrhea, alopecia, bony de- formities, and short stature. She was born to healthy nonconsanguineous parents. The father is from Louisiana and the mother from Texas. The father was 21 years old and the mother 18 a t the time of birth. The proposita has 2 paternal half-sibs who are healthy. The family history is unremarkable except for the an- tecedent of a paternal second cousin with von Hippel- Lindau syndrome. Prenatal and natal history were unremarkable except for the antecedent of breech pre- sentation. Growth and psychomotor development were normal. At the age of 6 years, when she started school, the patient was considered to be a normal girl. Concern began around age 9y2 years when she started loosing her hair. She noticed progressive loss of scalp hair and eyebrows over a 6-month period (Fig. 1). A few months later, she began to have recurrent and painful cramps in the calves and thighs. They were induced by physi- cal exercise or emotional distress, but not associated with any changes in sensorium. They lasted for a few minutes and on a few occasions the whole day. With time, these cramps became more severe and frequent, involving the whole body musculature, including ab- domen, upper limbs, and the face. Within the last 2 years, she developed problems with swallowing sec- ondary to spasms in the masticatory muscles. Muscle relaxants have not had a favorable effect. Growth re- tardation and progressive skeletal deformities of both knees and wrists, and limitation of movements of the right shoulder became evident after age 10. The defor- mity of both knees caused difficulty in walking. For this reason, she had 5 operations on knees and ankles be- tween the age of 14 and 19 years. In April 1993, the pa- tient sustained a fracture of the right leg with impaired healing. For this reason, an osteotomy of the femur was performed in December 1993, and an electrical bone growth stimulator was placed in March 1994 at another

  • Satoyoshi Syndrome 621

    appearance (Fig. 2e). There were extra finger flexion creases on the left middle and right index fingers. Breast development was normal, but her uterus was hypoplastic; the adnexa were not palpated. Cranial nerves were intact. There were no motor or sensory ab- normalities. Myoclonic jerks were frequent during the examination.

    Complete blood count (CBC) was normal as was he- moglobin AX, erythrocyte sedimentation rate (ESR), urinalysis test, serum electrolytes (including serum calcium and phosphorus), serum aldolase, liver func- tion tests, and urine myoglobin. Creatine phospho- kinase was mildly elevated at 241 IU/1 (normal range: 24-235 IU/l). Serum T3, T4, and thyroid-stimulating hormone (TSH), serum cortisol, progesterone, estra- diol, prolactin, somatomedin C, IGF binding protein, and follicle-stimulating hormone (FSH) were normal. Luteinizing hormone (LH) was low (0.18 mIU/ml). Im- munological work-up showed normal levels of serum immunoglobulins (IgM, IgG, and IgA), IgG subclasses, total complement activity, C3 and C4. Autoantibodies, such as antinuclear antibodies (ANA), anticholine es- terase antibodies, antithyroid microsomal antibodies, antithyroglobulin antibodies, anti-intrinsic factor anti- bodies, antireticulin antibodies, and antiovary antibod- ies were absent. Serum IgE was elevated, at 342 IU/ml (normal < 158 IU/ ml). Candida intradermal skin test was nonreactive. Lymphocyte subpopulation study showed decreased natural killer cells (CD56) and ele- vated CD4/CD8 ratio. D-xylose, lactose breath hydro- gen test, 3-day stool fat, and upper gastrointestinal (GI) endoscopy and biopsies were all normal.

    Radiological examination demonstrated multiple metaphyseal lesions with striking slipping of epiphyses on proximal humeri and femora, distal radii and ulnae (different from a Madelung deformity), left knee (the right knee was recently operated on), and both ankles (Fig. 3). The skull and spine radiographs were normal. Head computed tomographic (CT) scan was normal. U1- trasonography of the pelvis showed hypoplastic uterus.

    With the diagnosis of Satoyoshi syndrome, treatment with prednisone [Yamagata et al., 1991; Kuru et al., 19921 was initiated with a dose of 60 mg/m2 every other day. Muscle spasms improved after 4 weeks and totally disappeared by the 8th week of treatment; hair growth was noticed after 6 weeks of treatment, and 2 episodes of light vaginal bleeding were observed during the first 3 months of treatment.

    Fig. 1. a,b: The patient at age of 7% and 9Yu years, respectively. c,d: The patient a t 9 % ~ years with incipient alopecia.

    hospital. Between the age of 14 and 15, she underwent normal breast development but had no periods. After age 18, because of primary amenorrhea, her mother provided birth control pills for 4 months during which time the patient had normal cycles. In previous genetic and endocrinological evaluations, a small uterus, non- identifiable ovaries, and low growth hormone levels were reported. A prometaphase chromosomal study was done in 1993 with normal results.

    Examination a t age of 19Y~ years showed a n alert, in- telligent woman with normal facial appearance, alo- pecia, and short stature (137 cm, 4 t h centile) with de- creased arm span (128.5 cm) and rhizomesomelic shortness of limbs (Fig. 2a-c). Weight was 43.6 kg (

  • 622 Ehlayel and Lacassie

    Fig. 2. a: The patient a t age of 14 years wearing a wig and showing short stature with short limbs. b, c: Patient at 19 years. d: Wrist deformity. e: Fingers presenting drumstick deformity.

    et al., 1982, 19831. The response of the muscular spasms [Samagata et al., 1991; Kuru et al., 19921, amenorrhea, and alopecia to glucocorticoids [Samagata et al., 19911, the association of some cases with myas- thenia gravis [Satoh et al., 1982, 19831, nephritis [Satoyoshi, 19781, idiopathic thrombocytopenia [Sama- gata et al., 19911, and the deposition of immune com- plexes a t the motor end plate of biceps muscle [Satoh et al., 19831, low IgG [Kuru et al., 19921, and positive ANA of speckled pattern [Samagata et al., 19911 fur- ther support this hypothesis [Yamagata et al., 1991; Kuru et al., 19921. However, an extensive immunologi- cal evaluation in our patient did not show any de- tectable autoimmune abnormality. The muscle spasms seem to play a role in the production of skeletal abnor- malities [Ikegawa et al., 1993b1. The spasms have been associated with the presence of diarrhea, raising the possibility that this disease is a variety of malabsorp- tion syndrome [Satoyoshi and Samada, 1967; Sato- yoshi, 1978; Merello et al., 19941. However, in our patient, an extensive GI evaluation ruled out malab- sorption.

    Since most patients have been reported in the Japan- ese literature with only a few references in non-Asian

    journals, this syndrome is not included in most genet- ics, neurology, and orthopedic references despite its striking anomalies [Jones, 1988; Swaiman, 1989; Tachdjian, 1990; Baraitser and Winter, 19931. Patients with this condition are considered normal a t birth and infancy, The characteristic phenotype usually appears after the first decade of life.

    The Phenotype Clinically this syndrome is characterized by:

    1. Progressive painful intermittent muscle spasms starting between the ages of 6-15 years with an av- erage age of onset of 10.6 years [Satoyoshi, 19781. However, in