Langerhans cell histiocytosis: retrospective analysis of 217 cases in a single center.

Langerhans cell histiocytosis (LCH) is a disorder with unclear etiology and pathogenesis, which is characterized by abnormal clonal proliferation and accumulation of langerhans cells at various tissue and organs. A total of 217 patients with LCH were evaluated retrospectively for clinicopathological features, laboratory findings, treatment modalities, long-term outcome, and factors affecting the outcome. Median age at the time of diagnosis was 3.5 years and male/female ratio was 1.8. The most common complaint at presentation was a bone lesion-related symptom. Fifty percent of the patients younger than 2 years had organ dysfunction (OD). Treatment consisted of surgery, chemotherapy, and radiotherapy alone or in combination. Vinblastine with or without prednisolone was the most common used chemotherapy regimen. Overall (OS) and event-free survival (EFS) rates were 84% and 51.5%, respectively, at an 8-year median follow-up time. Overall survival was significantly lower in patients younger than 2 years of age and patients with OD. The age at diagnosis, pulmonary, liver, or hematological involvement, and elevated acute-phase reactants were found to have a statistically significant effect on the OS or EFS rates.

Immunohistochemical detection of Helicobacter pylori infection in gastric biopsies of urea breath test-positive and -negative pediatric patients.

Helicobacter pylori (H. pylori) is a common cause of gastritis in both children and adults, and its incidence increases every year. The aims of this study were to evaluate the histopathologic features of H. pylori gastritis and to compare immunohistochemical with histochemical [hematoxylin-eosin (HE) and Giemsa] staining of gastric biopsy specimens for the detection of H. pylori infection from urea breath test (UBT) (-) and UBT (+) children. Seventy-eight gastric biopsies from pediatric patients who were administered UBT were included in this study. Gastric biopsy specimens were evaluated histopathologically and graded according to the Sydney system. HE, Giemsa and immunohistochemical staining was performed for the identification of H. pylori. The frequency of H. pylori gastritis was higher in the antrum than corpus. All biopsies with H. pylori colonization showed chronic inflammation with activity. By using immunohistochemical method, coccoid forms of H. pylori and spiral bacteria with low density were observed easily. With histochemical staining, 1/10 (10%) UBT (-) biopsies were H. pylori (+), while with immunohistochemical staining, 3 of the biopsies from UBT (-) patients were found to be H. pylori (+). Biopsies from 65 of 78 (83.3%) UBT (+) patients were H. pylori (+) with histochemical staining, but only 53 of these biopsies were found to be H. pylori (+) immunohistochemically. We conclude that immunohistochemical staining is more specific than histochemical staining and UBT for the detection of H. pylori infection.

Renal cell carcinoma in children: experience of a single center.

OBJECTIVE: To evaluate the clinical features and outcome of children with renal cell carcinoma (RCC). PATIENTS AND METHODS: Eleven patients with RCC who were diagnosed between 1972 and 2004 were retrospectively analyzed. Clinical features, histopathology, treatment regimens and outcomes of the patients were evaluated. RESULTS: The male/female ratio was 3:8, with a median age of 10 years. The stage distribution was as follows: 3 patients in stage I, 1 patient in stage II, 3 patients in stage IIIb, and 4 patients in stage IV. Five of 7 patients with stage II-IV received an actinomycin D-based regimen, one received a cisplatin-based regimen, and the other was given 5-fluorouracil (5-FU). In the last patient, interferon-alpha was given in combination with 5-FU; 1 of the patients on the actinomycin D regimen received interferon-alpha as well. All of the stage I patients are alive without disease. Three patients with stage IIIb, stage IV and stage II disease are alive without disease 8, 14 and 26 years after their diagnosis, respectively. The other stage IV and stage IIIb patients died of the disease. CONCLUSION: Nephroureterectomy is the main treatment modality, and it is sufficient for stage I patients. For patients with stage II-IV RCC, interferon-alpha and/or actinomycin D-based chemotherapy is the treatment of choice.

Extranodal type T/NK-cell lymphoma with an atypical clinical presentation.

Peripheral-type natural killer (NK)- or T-cell lymphomas are rare disorders characterized with clonal proliferation of mature lymphocytes. They have been linked to chronic and active Epstein-Barr virus infection (CAEBV), which itself is not defined as a malignant hematological disorder. The authors present a patient with T/NK-cell lymphoma involving skin, kidneys, spleen, pancreas, and meninges. She was remarkable for having the mosaic feature of more than one type of extranodal T/NK-cell lymphoma. She also had mixed findings of CAEBV that might have been attributed both to hypersensitivity to mosquito bites and to hemophagocytic lymphohistiocytosis.

Simple cyst of the testis: a rare and benign cause of testicular swelling in infancy.

We report a five-month-old boy who was referred to the hospital with a presumptive diagnosis of hydrocele of the cord. Ultrasonography revealed a cystic mass within the left testis. A complete removal of the cystic mass was done. Histopathological diagnosis was simple cyst of the testis. This rare lesion should be considered in the differential diagnosis of cystic testicular lesions in infancy. The treatment of choice is simple enucleation of the cyst with sparing of the testis and related structures.

Successful treatment of retroperitoneal giant cell-type malignant fibrous histiocytoma in a 5-year-old boy.

Malignant fibrous histiocytoma, usually seen in patients older than 10 years, is an aggressive soft-tissue sarcoma occurring mostly in the extremities and the trunk, but it is extremely rare in children. We report the clinical, radiological and pathologic features of a five-year-old boy who was diagnosed as a retroperitoneally originated malignant fibrous histiocytoma. The patient with unresectable mass was successfully treated with multidisciplinary approach, with chemotherapy, surgery and radiotherapy, by using combined chemotherapy consisting of vincristine, cisplatinum, adriamycin, cyclophosphamide, actinomycin D and dacarbazine.

Late recurrence in children with Wilms' tumor.

We aimed in this study to evaluate the clinical and radiological features of the late recurrence of Wilms' tumor in children. Among 553 children diagnosed with Wilms' tumor between 1972 and 2004, four cases were determined to be late recurrences. Clinical, histopathological parameters, treatment details, and outcomes of the patients were evaluated retrospectively. The ages of the patients at the time of diagnosis were 2, 5, 5, and 9 years and the male/female ratio was 1/3. Two patients had stage II disease and two had stage IV characteristics. Histopathological examination showed favorable histology in all of the patients. Initial treatment was surgery and chemotherapy, which included vincristine and actinomycin-D. Abdominal radiotherapy was performed in two patients. Recurrence times were 36, 41, 51, and 96 months. Local recurrence and lung metastasis were detected in two patients, local recurrence in one, and lung nodules in the fourth patient. At the time of relapse, the chemotherapy protocols were as follows: vincristine, actinomycin-D, adriamycin, and cyclophosphamide in two patients; vincristine, actinomycin-D, and epirubicin in one patient; and vincristine, actinomycin-D, and adriamycin in the last patient. In the cases with late local recurrence, one patient had a local spillage and one patient had regional lymph node involvement. Although the other patient had local spillage, regional lymph node involvement, and renal artery invasion, isolated lung recurrence was observed. Only one patient had progressive disease and is still under treatment, whereas the other patients died with disease. Major recurrence sites were both local and the lungs. All of the patients had regional features including spillage, regional lymph node involvement, and vascular or capsular involvement. Late recurrence in patients with Wilms' tumor is a poor prognostic factor and should be treated with an intensified regimen.

Histone mRNA in situ hybridization and Ki 67 immunohistochemistry in pediatric adrenocortical tumors.

Adrenocortical tumors in the pediatric population are rare. Classification of these tumors as adenomas or carcinomas using histological criteria is often difficult. Immunohistochemical expressions of proliferative markers are currently under investigation for utilization in the differential diagnosis and prediction of clinical outcomes. The value of histone proteins as prognostic markers in adrenocortical tumors has not yet been elucidated. We evaluated the histological features, immunohistochemical staining of Ki 67, and in situ hybridization for histone mRNA in 30 pediatric adrenocortical tumors. We investigated the relationship between these parameters and the prognosis. Using the classification proposed by Weiss, 19 tumors were classified as carcinomas and 11 as adenomas. Ki 67 and histone mRNA labeling indices (LIs, the percentage of Ki 67-positive and histone mRNA-positive tumor cells, respectively) were significantly higher in carcinomas than in adenomas (Ki 67 LI was 14.62+/-5.79 in adenomas and 20.35+/-6.23 in carcinomas, p=0.02. Histone mRNA LI was 1.73+/-1.71 in adenomas and 6.62+/-2.28 in carcinomas, p=0.00). The proliferative activity assessed by histone mRNA was lower than that assessed by Ki 67 in both diagnostic groups. The cut off point for the diagnosis of malignancy was found to be 14.55 for Ki 67 LI and 5.75 for histone mRNA LI. A correlation was found between a histone mRNA LI>or=5 and poor prognosis (recurrence, metastasis, or death). We concluded that the proliferative activity of the tumor assessed by Ki 67 and histone mRNA may assist in differentiating adrenocortical adenomas and carcinomas. In addition, our results suggest that the most reliable parameter to predict prognosis in pediatric adrenocortical tumors is the histone mRNA LI.

Histological response to injected gluteraldehyde cross-linked bovine collagen based implant in a rat model.

BACKGROUND: The aim of present study is to investigate the short and long term histopathological alterations caused by submucosal injection of gluteraldehyde cross-linked bovine collagen based on an experimental rat model. METHODS: Sixty Sprague-Dawley rats were assigned into two groups as group I and II each containing 30 rats. 0.1 ml of saline solution and 0.1 ml of gluteraldehyde cross-linked bovine collagen were injected into the submucosa of bladder of first (control) and second groups, respectively. Both group I and II were further subdivided into 3 other groups as Group IA, IB, IC and Group IIA, IIB, IIC according to the sacrification period. Group IA and IIA, IB and IIB, IC and IIC rats (10 rats for each group) were sacrificed 3, 6, and 12 months after surgical procedure, respectively. Two slides prepared from injection site of the bladder were evaluated completely for each rat by being unaware of the groups and at random by two independent senior pathologists to determine the fibroblast invasion, collagen formation, capillary ingrowth and inflammatory reaction. Additionally, randomized brain sections from each rat were also examined to detect migration of the injection material. The measurements were made using an ocular micrometer at x10 magnification. The results were assessed using t-tests for paired and independent samples, with p < 0.05 considered to indicate significant differences; all values were presented as the mean (SD). RESULTS: Migration to the brain was not detected in any group. Significant histopathological changes in the gluteraldehyde cross-linked bovine collagen injected groups were fibroblast invasion in 93.3%, collagen formation in 73.3%, capillary ingrowth in 46.6%, inflamatory reaction in 20%. CONCLUSION: We emphasize that the usage of gluteraldehyde cross-linked bovine collagen in children appears to be safe for endoscopic treatment of vesicoureteral reflux.

Severe lethal spinal muscular atrophy variant with arthrogryposis.

Spinal muscular atrophies are a clinically and genetically heterogeneous group of disorders. Atypical forms of the disease have also been described, including those with associated sensory deficits, hearing loss, cerebellar hypoplasia, congenital heart defects, arthrogryposis, and bone fractures at birth. The patient described here is a male infant, born to a 30-year-old mother at 34 weeks of gestation complicated with polyhydramnios. The first son of consanguineous parents had died with the same clinical features. The patient required ventilatory support because of respiratory failure after the birth and died on day 13. His physical examination revealed profound generalized hypotonia, absence of deep tendon and neonatal reflexes, dysmorphic facies, arthrogryposis, clinodactyly, and left femur fracture. A muscle biopsy revealed variation in fiber size with occasional hypertrophic fibers. The postmortem examination revealed loss and degeneration of anterior horn cells. We propose that the patient, who presented with severe hypotonia, femur fracture, arthrogryposis, dysmorphic features, history of early death of his brother with the same clinical features and parental consanguinity, had probable X-linked spinal muscular atrophy. However, autosomal-recessive inheritance can not be completely excluded.

Noncardiac malformations in congenital heart disease: a retrospective analysis of 305 pediatric autopsies.

Congenital heart disease (CHD) is one of the important groups of birth defects and contributes significantly to infant mortality. Extracardiac anomalies occur in 15-45% of cases with CHD. In this retrospective study, autopsies of cases born alive and diagnosed as CHD between 1977-2002 at Hacettepe University Ihsan Dogramaci Children's Hospital, Pediatric Pathology Department, were investigated. In this period, a total of 3320 autopsies were performed and the incidence of CHD was 9.1%. The most commonly encountered CHD was ventricular septal defect (VSD) (15.3%). In 45.9% of cases, one or more extracardiac malformations were present. The most commonly encountered extracardiac malformation was craniofacial malformations. Less commonly seen were malformations of genitourinary, musculoskeletal, respiratory, gastrointestinal, central nervous systems and spleen anomalies. Ventricular septal defect, atrial septal defect (ASD), aortic coarctation, single ventricle, pulmonary stenosis, hypoplastic right heart syndrome, double outlet right ventricle, ASD+VSD, aortic arcus anomalies, and right and left atrial isomerism cases were often (>50%) accompanied by extracardiac malformations. No extracardiac malformations were detected accompanying pulmonary atresia with intact interventricular septum, Ebstein malformation, and mitral stenosis (MS). Spleen malformation was significantly high in cases with single ventricle (p<0.002). The anomalies of the gastrointestinal and genitourinary systems were found to be frequently associated with conotruncal heart defects (p<0.001). In the group with transposition of the great arteries, noncardiac malformations were present in only three cases (10%), differing from the rest of the material (p<0.001). In conclusion, when a heart malformation is detected in a patient, a detailed investigation should be done on extracardiac malformations or vice versa. Proper identification and treatment of CHD early in the prenatal period will save the family from the economic and emotional burden caused by having such a child with CHD.

Prenatal echocardiographic diagnosis of congenital heart disease: comparison of past and current results.

The increased experience in interpretation of fetal echocardiographic images may change the accuracy of fetal echocardiography in diagnosing fetal heart defects. We thus decided to evaluate the specificity and the sensitivity of our fetal echocardiographic examinations in diagnosing congenital heart disease, focusing especially on the outcome of complex cardiac pathologies. Between October 1999 and July 2003, 642 fetuses were followed until birth and underwent a postnatal reassessment of the cardiovascular system in our institution. These cases constitute our cohort. The postnatal reassessment was mainly done by echocardiography; some cases also had angiography. In case of intrauterine or postnatal death, an autopsy was performed. The prenatal and postnatal diagnoses were compared, and specificity and sensitivity of fetal echocardiography for congenital heart pathologies were determined. Among 45 affected pregnancies, 31 cases had complex and 14 had significant cardiac defects. The sensitivity of fetal echocardiography for cardiac anomalies was 93.3%; the specificity was 100%. Compared to our previous study, the sensitivity was remarkably improved (in our previous study sensitivity was 78% and specificity 100%). Echocardiography is a very useful and reliable tool in the evaluation of the fetal cardiovascular system, and has high sensitivity and specificity for congenital heart diseases.

The triad of nesidioblastosis, congenital neuroblastoma and glomerulocystic disease of the newborn: a case report.

Neuroblastoma is the most common malignant tumor of the newborn, comprising 20% of all malignancies encountered during the neonatal period. We herein report a newborn who was born after 29 weeks' gestation and died unexpectedly at the 12th hour of life with no response to vigorous cardiopulmonary resuscitation. Autopsy findings revealed a right pararenal mass; microscopic examination showed neuroblastoma. Although the pancreas was grossly normal, its microscopic sections revealed a reduced number of islets of Langerhans and dispersion of the islet cells throughout the exocrine cells of the pancreas, and immunocytochemistry for the pancreatic hormones confirmed the dispersion of the islet cells. Final pathologic interpretation thus concluded the presence of nesidioblastosis. Furthermore, microscopic examination of the kidney showed glomerulocystic disease. Although the association of congenital neuroblastoma and nesidioblastosis has recently been defined as a new complex, neurocristopathy, the triad of congenital neuroblastoma, nesidioblastosis and glomerulocystic disease of the newborn has not been reported previously. To our knowledge, our case is the first reported newborn presenting with this triad. In conclusion, the association of nesidioblastosis and/or renal glomerulocystic disease should be kept in mind when encountering a case of congenital neuroblastoma. However, whether the presence of glomerulocystic disease in association with those other neurocristopathic pathologies is a coincidental finding or shares a common pathophysiological mechanism remains to be determined.

Hodgkin's disease and ataxia telangiectasia with pulmonary cavities.

Ataxia telangiectasia (AT) homozygotes have an increased risk for development of Hodgkin's disease (HD). Parenchymal lung involvement is not uncommon in HD; however, cavitary pulmonary lesions are quite unusual. We report on 3 cases of AT with HD who had mediastinal disease and parenchymal pulmonary involvement with cavitation. Of 6 AT patients in our HD series, 3 developed pulmonary cavities. The patients displayed pulmonary infiltration, cavitation in the lung parenchyma, and mediastinal enlarged lymph nodes on both plain chest X-rays and thoracic computed tomographies. No infectious etiologies were established for the pulmonary findings. Histopathological examination of open lung and mediastinal biopsies revealed HD, and all patients received multiagent chemotherapies. The outcome was fatal in all 3 patients. Respiratory infections are the principle cause for morbidity and mortality in AT patients. Reports on cavitating pulmonary lesions in HD are quite rare. Furthermore, data regarding the patterns of pulmonary involvement in AT patients with or without HD are lacking. The increased incidence of malignancies in AT patients may relate to immunodeficiency and to the chromosomal alterations identified.

A huge gastric stromal tumor in a 13-year-old girl.

A 13-year-old girl presenting with severe anemia was diagnosed to have a large gastric tumor protruding toward the antrum with two central ulcerations. Partial gastrectomy including antrectomy and gastroduodenostomy were performed. Histologic and immunohistochemical studies revealed one of the most uncommon gastric tumors in children; a gastrointestinal stromal tumor. Close follow-up of the patient with endoscopy, abdominal ultrasonography and/or computed tomography in three to six month intervals revealed no recurrences or metastasis of the tumor following its complete excision.

A case of homozygous familial hypercholesterolemia with focal segmental glomerulosclerosis.

Familial hypercholesterolemia (FH) is a common autosomal dominant inherited disorder characterized by increased levels of circulating plasma low-density lipoprotein cholesterol (LDL-C), tendon xanthomas, and premature atherosclerotic cardiovascular disease. Homozygous FH occurs in only one in a million people. Focal segmental glomerulosclerosis (FSGS) is clinically characterized by proteinuria, which is marked in the majority of cases and accompanied by nephrotic syndrome, high incidence of hypertension, and progression to renal failure. To our knowledge, we herein report for the first time a case of homozygous FH associated with FSGS. A seven-and-a-half-year-old boy was referred to our hospital due to cutaneous xanthomata and growth retardation. He had multiple nodular yellowish cutaneous xanthomatous lesions each 1 cm in size over his knees and sacral region. Laboratory data included cholesterol level of 1,050 mg/dl, low density lipoprotein cholesterol (LDL-C) 951 mg/dl, high-density lipoprotein cholesterol (HDL-C) 29 mg/dl, triglycerides 168 mg/dl, total protein 6.3 g/dl, and albumin 3.2 g/dl. Urinary protein excretion was 78 mg/m(2) per hour. A percutaneous renal biopsy was performed, and histological findings showed FSGS. Treatment with cholestyramine and atorvastatin was unsuccessful in terms of lowering lipids, and he was placed on weekly sessions of plasmapheresis. Total cholesterol was reduced from 1,050 mg/dl to 223 mg/dl, LDL-C from 951 mg/dl to 171 mg/dl, and urinary protein excretion from 78 mg/m(2) per hour to 42 mg/m(2) per hour after eight sessions of plasmapheresis. It is our belief that plasmapheresis is a treatment of choice in patients with FSGS associated with FH.

Histological response to injected dextranomer-based implant in a rat model.

To investigate the short and long term histopathological alterations caused by submucosal injection of dextranomers in sodium hyaluronan (DiHA) based on an experimental rat model. Sixty Sprague-Dawley rats were assigned into two groups as group I and II, each containing 30 rats. Totally 0.1 ml of saline solution and 0.1 ml of DiHA were injected into the submucosa of bladder of first (control) and second groups, respectively. Both group I and II were further subdivided into three other groups as Group IA, IB, IC and Group IIA, IIB, IIC according to the sacrificial period. Group IA and IIA, IB and IIB, IC and IIC rats (ten rats for each group) were sacrificed 3, 6, and 12 months after surgical procedure, respectively. Two slides prepared from injection site of the bladder were evaluated completely for each rat by being unaware of the groups and at random by two independent senior pathologists to determine the fibroblast invasion, collagen formation, capillary growth and inflammatory reaction. Additionally, randomized brain sections from each rat were also examined to detect migration of the injection material. The measurements were made using an ocular micrometer at 10x magnification. The results were assessed using t-tests for paired and independent samples, with P<0.05 considered to indicate significant differences; all values were presented as the mean (SD). Migration to the brain was not detected in any group. Significant histopathological changes in the DiHA injected groups were granuloma formation in 43.3%, foreign body type giant cells in 76.6%, inflammatory infiltration in 100%, and fibroblasts surrounding microspheres in 100% of the rat bladder. The interaction between granuloma formation and long-term tissue effects in children is still obscure. We emphasize that further prospective human (and/or animal) studies are required to clarify the long-term effects of granuloma formation with regard to clinical applications.

Improved survival of children with wilms tumor.

To analyze changes in the overall survival (OS) rate of children with Wilms tumor treated in a single institute over nearly 30 years. This study included 327 children with a newly diagnosed Wilms tumor. Their median age was 3 years, and the male:female ratio was 1.1. Survival rates were analyzed according to the stage of disease, histopathology, and different treatment regimens used between 1972 and 1999. At diagnosis, 51.1% of patients had advanced stage disease. Ten patients had anaplasia, and; 97% (317 patients) of the tumors had favorable histopathology. The 10-year OS rate was 60.6% for the entire group, but varied according to the years in which the patients were treated, the chemotherapy regimen, and stage of disease. Patients treated during the periods of 1972 to 1979, 1980 to 1989, and 1990 to 1999 had 10-year OS rates of 48.5%, 64.3%, and 72.8%, respectively. The 10-year OS rate in children treated with actinomycin only was 36.7% compared with 48% for children treated with the actinomycin-D+vincristine regimen with a 3-month interval, 67% for the actinomycin-D+vincristine regimen with a 1.5-month interval, 54.5% for the poor-risk regimen (actinomycin-D, vincristine, cyclophosphamide, and adriamycin), and 53.4% for the SIOP-9 protocol. Children with stage I to IV disease had 10-year OS rates of 75%, 77.1%, 54.4%, and 30.4%, respectively. The 10-year OS rates for children with stage III and IV disease increased from 46.4% and 13.4% for patients treated between 1972 to 1979 period to 75% and 54.5% for children treated during 1990 to 1999. The 10-year OS rate for children with Wilms tumor improved as treatment strategies evolved, illustrating that pediatric oncology in Turkey is developing parallel to the Western world.

Paratesticular metastasis from Wilms tumor associated with a hydrocele.

Metastatic sites other than the lungs, lymph nodes, and liver are unusual for Wilms tumor (WT). Intra-scrotal metastasis is very rare. We report a 3-year-old boy with stage IIA WT, who experienced paratesticular metastasis 2 months after surgery for an abdominal recurrence. He had right scrotal hydrocele at initial diagnosis. The patient underwent right radical orchiectomy, and pathological examination revealed paratesticular WT metastasis. Intra-abdominal and peritoneal disseminated metastases followed. We considered that tumor cells spread through the patent processus vaginalis and grew at paratesticular space in hydrocele. One month after the end of 12 months of salvage chemotherapy and abdominal radiotherapy, the patient has no evidence of disease.

Calpain-3 mutations in Turkey.

Autosomal recessive limb-girdle muscular dystrophies (LGMD2s) are a clinically and genetically heterogeneous group of disorders, characterized by progressive involvement of the proximal limb girdle muscles; the group includes at least 10 different genetic entities. The calpainopathies (LGMD2A), a subgroup of LGMD2s, are estimated to be the most common forms of LGMD2 in all populations so far investigated. LGMD2A is usually characterized by symmetrical and selective atrophy of pelvic, scapular and trunk muscles and a moderate to gross elevation of serum CK. However, the course is highly variable. It is caused by mutations in the CAPN3 gene, which encodes for the calpain-3 protein. Until now, 161 pathogenic mutations have been found in the CAPN3 gene. In the present study, through screening of 93 unrelated LGMD2 families, we identified 29 families with LGMD2A, 21 (22.6%) of which were identified as having CAPN3 gene mutations. We detected six novel (p.K211N, p.D230G, p.Y322H, p.R698S, p.Q738X, c.2257delGinsAA) and nine previously reported mutations (c.550delA, c.19_23del, c.1746-20C>G, p.R49H, p.R490Q, p.Y336N, p.A702V, p.Y537X, p.R541Q) in the CAPN3 gene. There may be a wide variety of mutations, but clustering of specific mutations (c.550delA: 40%, p.R490Q: 10%) could be used in the diagnostic scheme in Turkey.