Pediatr Radiol (2003) 33: 216–218 DOI 10.1007/s00247-002-0852-y
Anna Tylki-Szyman´ska Antoni Pyrkosz Małgorzata Krajewska-Walasek Jacek Michałkiewicz Aleksandra Kowalska Dariusz Rokicki
Received: 10 December 2001 Accepted: 9 October 2002 Published online: 10 December 2002 Ó Springer-Verlag 2002
A. Tylki-Szyman´ska (&) Æ D. Rokicki Department of Metabolic Diseases, The Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04730, Warsaw, Poland E-mail:
[email protected] Tel.: +48-22-8157490 Fax: +48-22-8157489 A. Pyrkosz Department of Genetics, Silesian Medical Academy, Katowice, Poland
CASE REPORT
Schimke immuno-osseous dysplasia: two cases
Abstract We report two patients with Schimke immuno-osseous dysplasia (SIOD). SIOD is characterised by growth retardation, renal failure, spondylo-epiphyseal dysplasia, specific phenotype and defective cellular immunity. These two children demonstrated a bone dysplasia with characteristic radiographic appearances. We postulate that SIOD should be considered in all cases of growth failure with an unclassifiable bone dysplasia. Repeated urine tests for proteinuria could be helpful in reaching the correct diagnosis.
Keywords Schimke immunoosseous dysplasia
M. Krajewska-Walasek Department of Genetics, The Children’s Memorial Health Institute, Warsaw, Poland J. Michałkiewicz Department of Immunology, The Children’s Memorial Health Institute, Warsaw, Poland A. Kowalska Department of Radiology, The Children’s Memorial Health Institute, Warsaw, Poland
Introduction Osseous dysplasia, rapidly progressive renal insufficiency beginning with steroid-resistant nephrotic syndrome, episodes of lymphopaenia and immune deficiency related to T-cell dysfunction are characteristics of Schimke immuno-osseous dysplasia (SIOD) [1]. Patients affected
by this syndrome are marked by a severe growth deficit caused by osseous dysplasia [2]. Their phenotype is also distinctive: barrel chest, long arms with rather large hands, low-set large ears, prominent nose with a bulbous tip, fine hair, pigmented spots on the skin, high-pitched voice and photophobia. Mental development is normal. The age at onset of nephrotic syndrome is the basis for
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distinguishing early- and late-onset forms. The development of nephrotic syndrome is important since from this point, deterioration of renal function is rapid and complicated by recurrent serious infections related to immune deficiency. Reported cases of this syndrome among siblings suggest an autosomal recessive mode of inheritance [1]. Boerkoel et al. [2] summarised the clinical findings extracted from published and unpublished data of 39 patients with SIOD. They found a high incidence of thyroid dysfunction, bone marrow hypoplasia, pancytopaenia, cerebral ischaemia and lack of response to medical therapy. We present two cases of SIOD; the first patient is currently 3 years old and the second was diagnosed 10 years after her death based on a detailed medical history. These cases can be classified as the early-onset form of SIOD with a severe course.
Case reports Case 1 M.N., a boy nearly 3 years of age, was born as the second child of healthy, non-consanguineous parents at 38 weeks’ gestation by spontaneous delivery. Birth weight was 1,600g and length was 45 cm. US monitoring during pregnancy showed a severe growth deficit, but motor and mental development are currently normal. Significant weight and height deficits have continued from birth; he grew until the sixth month of life, but subsequently, growth has been minimal. In addition to nanosomia, the boy’s phenotype is characterised by a short trunk, barrel chest, short neck, relatively long upper extremities, and large hands and feet (Fig. 1a). His face is peculiar, with deeply set eyes, strabismus, broad depressed nasal bridge, bulbous nose tip, very weak fine hair, and his voice is highpitched and shrill. Internal organs are normal. He is not prone to infections. Additional examinations have twice revealed mild proteinuria. Radiographs have shown mild non-specific spondylo-epiphyseal dysplasia, minimal platyspondyly, oval-shaped vertebral bodies, unossified proximal femoral epiphyses, short femoral necks of reduced density, retarded carpal bone age and shortened middle phalanges of fingers II and V (Fig. 2). Immunological testing has revealed profound cellular immunity deficit and a nearl-complete lack of T lymphocytes. The patient has a profound lymphopaenia (23% as a proportion with an absolute count of 1,231/ll vs. 45% and 3,268/ll in controls). The distribution of peripheral blood lymphocyte subpopulations (using double colour-flow cytometry) showed a decrease in the proportion of the total (CD3+) T-cell subset (26%), a very low proportion of helper CD4+ cells (8%), and a decreased CD8+ T-cell subset (13%). Case 2 A.S. was the first child of non-consanguineous parents, although they come from the same village. The girl presented to our institute in 1981, at 11 months of age, because of growth failure and lack of weight gain since 6 months of age. Mental and motor development were normal, but her growth and weight deficit were very marked. She had a distinctive phenotype: wide nose with a bulbous tip, lowset large ears, convergent strabismus, and fine weak hair. Her
Fig. 1a, b Clinical photographs. a Case 1. Note the peculiar face with broad depressed nasal bridge, bulbous tip of nose and weak fine hair. The patient has a short trunk and neck, long extremities and large hands and feet. b Case 2. Note the wide nose with a bulbous tip, low-set large ears and fine weak hair. The patient has a barrel chest, short neck and relatively long extremities with large hands and feet
physique was characterised by a barrel chest, short neck, and relatively long upper extremities with large hands and large feet (Fig. 1b). The parents reported that the child showed photophobia and vomited frequently; she was not prone to infections. Laboratory studies were initially normal. Radiographs revealed an unclassifiable bone dysplasia. In the sixth year of life she developed what was initially slight proteinuria, but which by the eighth year of life developed into refractory nephrotic syndrome. Laboratory tests during that period revealed leucopaenia and anaemia on several occasions. Renal biopsy showed focal segmental glomerulonephritis; liver and bone marrow biopsies were normal. Nephrotic syndrome worsened in the ninth year of life, leucopaenia became persistent, and oral candidiasis developed. At the age of 9 years and 9 months, she developed fulminant pneumonia and died after a few days. The diagnosis of SIOD was made retrospectively, based on the striking phenotypic similarity with case 1 and on the girl’s detailed case history.
Discussion The presented cases of SIOD correspond with the descriptions of other authors [1, 2]. They can be classified, accepting the distinction between early and late forms, as the early form with a severe course. While not yet 3-years-old, case 1 already had proteinuria. Rapid progression of the disease should be expected, especially since he has a significant immunological deficit. Photophobia is present in both of our cases and is a feature
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recorded in the literature. Despite the profound immune deficit in both of our patients, infections did not dominate the clinical picture of either in their early years. In case 2, a serious infection was the direct cause of death; cyclical leucopaenia and anaemia had begun about 1 year earlier. In the cases presented here and those in the literature, growth inhibition and lack of weight gain were the first symptoms prompting presentation, even in the late-onset cases. The order in which the symptoms appeared in all of the cases is identical: growth inhibition, proteinuria, refractory nephrotic syndrome, renal failure, increase in infections, serious infections, and death. Authors reporting these cases have not focused on phenotype as suggestive of the diagnosis. In our case, the phenotype of case 1 pointed to a similarity with case 2 (Fig. 1). Radiographs of both children demonstrated similar appearances [3]. The results of immunological investigations indicated profound lymphopaenia that was dependent on the loss of the T-cell population (CD3+), with an elevated proportion and normal absolute numbers of the B-cell population. There are several known syndromes in which skeletal defects and nephropathy dominate (Jeune, Saldino-Maizner) [4, 5]. The suggestion of Spranger et al. [1] that SIOD is a multisystem disease, in which the underlying abnormality is a disorder of differentiation of chondrocytes and lymphocytes as the result of a regulatory gene defect, seems correct. SIOD appears to be a rare disorder, but it is possible that it is underdiagnosed. We postulate that SIOD should be considered in all cases of growth failure with an unclassifiable bone dysplasia. Repeated urine tests for proteinuria could be helpful in reaching the correct diagnosis.
Fig. 2a–c Case 1 at nearly 3 years of age. a Minimal platyspondyly and oval-shaped vertebral bodies with a small anterior tongue-like protrusion. b The proximal femoral epiphyses are not ossified; the femoral necks show reduced density. c Shortened middle phalanges of fingers II and V, small epiphyses, pseudo-epiphyses of metacarpal I and retarded carpal bone age
References 1. Spranger J, Hinkel GK, Stoss H, et al (1991) Schimke immuno-osseous dysplasia: a newly recognized multisystem disease. J Pediatr 119:64–72
2. Boerkoel CF, O’Neill A, Andre JL, et al (2000) Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and review of the literature. Eur J Pediatr 159:1–7 3. Bayer M, Baxova A, Olejar T, et al (1998) Schimke immuno-osseous dysplasia: a case report. Radiol Med 95:369– 371
4. Shah KJ (1980) Renal lesions in Jeune’s syndrome. Br J Radiol 53:432–436 5. Maizner F, Saldino RM, Ozonoff, et al (1970) Familial nephropathy associated with retinitis pigmentosa cerebellar ataxia and skeletal abnormalities Am J Med 49:556–562
