1/192. Familial cerebellar hypoplasia and pancytopenia without chromosomal breakages.Two siblings manifested a neuro-haematologic syndrome characterised by low birth weight, failure to thrive, chronic persistent tongue ulceration, severe truncal ataxia and pancytopenia without either telangiectasia or chromosomal instability. One sibling died from sepsis and the cerebellum demonstrated reduced cellularity of the molecular and granular layers with relative preservation of purkinje cells and minimal gliosis. A surviving sibling has shown haematologic progression to a myelodysplastic disorder. There was no evidence of any chromosomal instability following exposure of fibroblasts and lymphocytes to irradiation. monosomy-7 was not present in the surviving sibling. We suspect that these two patients represent another example of the rare Hoyeraal-Hreidarsson syndrome and we are currently engaged in very close monitoring of the surviving sibling for evidence of any karyotypic abnormality.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
2/192. Prenatal and postnatal management of hyperprostaglandin E syndrome after genetic diagnosis from amniocytes.OBJECTIVE: To describe prenatal genetic diagnosis in hyperprostaglandin E syndrome (HPS) and the effect of indomethacin therapy on the course of the disease before birth and in the neonatal period. methods: Mutational analysis of the ROMK channel gene (KCNJ1) from amniocytes by single-strand conformational analysis and direct sequencing. review of the clinical and laboratory findings during pregnancy and the neonatal period in two siblings affected with HPS. RESULTS: Compound heterozygosity of the fetus in KCNJ1 (D74Y/P110L) confirmed the clinical diagnosis of HPS at 26 weeks of gestation. indomethacin therapy from 26 to 31 weeks prevented further progression of polyhydramnios without major side effects. In contrast to the elder brother, who had been diagnosed at the age of 2 months, the neonatal course was uncomplicated. Hypovolemic renal failure after excessive renal loss of salt and water could be prevented and severe nephrocalcinosis did not occur. CONCLUSIONS: Genetic diagnosis of HPS and subsequent prenatal indomethacin therapy seems to have a beneficial effect on the natural course of HPS, especially progression of polyhydramnios; therefore, extreme prematurity could be prevented. Also, postnatally the early diagnosis allows the effective water and electrolyte substitution before severe volume depletion.- - - - - - - - - - ranking = 2keywords = progression (Clic here for more details about this article) |
3/192. The Dyggve-Melchior-Clausen syndrome.Two new cases of Dyggve-Melchior-Clausen syndrome are described; they belong to the fourth family from lebanon in which this disease has been recognized. There is no genealogical linkage between these four families. A particular feature in these cases is a striking rhizomelic shortness of the arms especially in one case. Clinical and radiological findings, progression of the skeletal changes are studied, along with the review of the cases in the literature. Cytological and biochemical data indicate that the DMC syndrome is not a mucopolysaccharidosis.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
4/192. Arteriovenous and lymphatic malformations, linear verrucous epidermal nevus and mild overgrowth: another hamartoneoplastic syndrome?We report a 22 year old female presenting with slowly progressive paraparesis, who appeared to have many (mainly subcutaneous) hamartomas. The neurological symptoms were caused by intraspinal masses and arteriovenous malformations. In addition, she had mild overgrowth of one leg and lymph vessel malformations. This combination of symptoms resembles proteus syndrome, but is different in symptomatology and progression and may be yet another hamartoneoplastic syndrome.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
5/192. Mutations of the adenomatous polyposis coli and p53 genes in a child with Turcot's syndrome.Turcot's syndrome is a rare heritable complex that is characterized by an association between a primary neuroepithelial tumor of the central nervous system and multiple colonic polyps. The aim of this study was to analyze genetic alterations in a case of Turcot's syndrome in a 10.5-year-old boy in whom a colorectal tumor developed 3.5 years following astrocytoma. An APC germline non-sense mutation at codon 1284 leading to a truncated protein was identified, as was a somatic p53 mutation in the colorectal carcinoma in exon 7, codon 244. The latter was not identified in the primary astrocytoma. However, immunohistochemistry revealed high p53 protein expression in both tumors, suggesting an additional p53 mutation in the primary astrocytic tumor. The diverse p53 mutations observed in this unique syndrome in two different sites and stages of the disease may shed light on the multistep progression of the malignant events.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
6/192. EEM syndrome: report of a family and results of a ten-year follow-up.We report on a Brazilian kindred in which two sibs presented with the complete form of EEM (ectodermal dysplasia, ectrodactyly, and macular dystrophy) syndrome with hypotrichosis, dental anomalies, syndactyly, and retinal changes with prominent pigmentation in the posterior pole of the retina. In this family, we also observed another sib with syndactyly, as well as a first cousin with ectrodactyly. A 10-year follow-up demonstrated gradually decreasing visual acuity and progression of retinal degenerative anomalies.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
7/192. A familial syndrome due to Arg648Stop mutation in the X-linked renal chloride channel gene.We describe a familial syndrome in two brothers who were investigated after the casual discovery of tubular proteinuria in their 1st month of life. During a follow-up of 20 and 11 years, respectively, the two children grew well and were asymptomatic, but developed the same biochemical abnormalities, i.e., tubular proteinuria and hyperphosphaturia, progressive decrease in serum phosphorus below the normal values for age, and an increase in serum 1,25-dihydroxyvitamin D levels over normal values. Moreover, hyperabsorptive hypercalciuria and systemic osteopenia developed and progressively worsened. In both children, at a different age, medullary nephrocalcinosis appeared. The oldest boy suffered a progressive decrease in urinary concentration ability and in glomerular filtration rate. Oral phosphate supplementation led to reversal of all biochemical abnormalities, with the exception of decreased phosphate tubular reabsorption and tubular proteinuria. With long-term phosphate supplementation, a normal bone mass was reached, while progression of nephrocalcinosis was arrested and impairment of renal function was slowed down. In a family study (siblings and parents), the only detectable abnormality was microglobinuria in the mother, thus suggesting a X-linked inheritance of this disorder. In the two probands a mutation within the renal chloride channel gene (CLCN5) was discovered.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
8/192. Transcriptional regulation of PDGF-A and TGF-beta by KTS WT1 deletion mutants and a mutant mimicking denys-drash syndrome.denys-drash syndrome (DDS) and frasier syndrome (FS) are rare diseases caused by the mutations of wilms tumor gene, WT1. The common denominator in these syndromes is a nephropathy which is manifested by early-onset proteinuria, nephrotic syndrome and end stage renal failure. Although these syndromes are genetic models of nephropathy and the mutations of WT1 gene are characterized in these patients the mechanism how mutations of WT1 gene affect the embryonic kidney adversely has not been elucidated. Recently, there was a report that FS is caused by mutations in the donor splice site of WT1. These mutations predicted loss of KTS isoform, which is one of the four splicing variants of WT1. In this study, two KTS deletion mutants of WT1 were made as well as a WT1 mutant mimicking a mutation found in a patient who had diffuse mesangial sclerosis, end stage renal failure and wilms tumor. Mutant embryonic kidney cell lines were established by transfection of 293 embryonic kidney cells with WT1 mutants. We investigated the transcription regulation of mutant WT1 among these cell lines using the reporter vectors containing PDGF-A and TGF-beta promoter sequence. Our results showed that the promoter activity of PDGF-A and TGF-beta, which are related to the progression of glomerular diseases, was modestly increased in the mutant cell mimicking the patent, while those activities were markedly increased in other two deletion mutant cell lines. This study demonstrated that KTS WT1 mutation found in DDS affected the cytokine expression adversely in vitro. From these results, we suggest that the alteration of KTS WT1 expression be responsible for the rapid progression of renal diseases in DDS and FS.- - - - - - - - - - ranking = 2keywords = progression (Clic here for more details about this article) |
9/192. Recurrent rectoneovaginal fistula caused by an incidental squamous cell carcinoma of the neovagina in Mayer-Rokitansky-Kuster-Hauser syndrome.OBJECTIVE: Mayer-Rokitansky-Kuster-Hauser syndrome is a congenital malformation characterized by an absence of the vagina associated with a variable abnormality of the uterus and the urinary tract but functional ovaries. Surgical correction requires the creation of a neovaginal canal by the performance of a neovaginoplasty and an accurate long-term application of an artificial phallus phantom to avoid secondary shrinkage of the canal. Due to the chronic alteration of the posterior neovaginal wall, ulcers and consecutive fistulae may occur. We report the clinical course of a female who required surgical intervention for a rectoneovaginal fistula and developed a recurrence of the fistula due to one of the extremely rare squamous cell carcinomas of the neovaginal epithelium in order to show potential diagnostic and therapeutic features. METHOD: The systematic report of a case is presented. RESULT: Almost 13 years following the initial construction of a neovagina the patient developed a single-tract rectoneovaginal fistula. After surgical repair she represented with a recurrence due to a vast squamous cell carcinoma of the former operation site. Tumor en bloc resection was performed and currently (follow-up: 4 months) she has no signs of new tumor progression. CONCLUSION: Creation of a neovagina is the standard procedure for treating vaginal atresia or aplasia. Because of the long clinical course postoperatively, complications may occur. This report of a case of a malignant transformation in neovaginal epithelium shows the potential risk of malignancy and underlines the necessity of a close follow-up.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
10/192. jaundice caused by the vanishing bile duct syndrome in a child with Hodgkin lymphoma.The authors report a 5-year-old boy with hodgkin disease and cholestatic jaundice that predated the start of treatment for his lymphoma. His clinical course was punctuated by relentless progression of jaundice, characterized by obstructive pattern liver function tests, severe pruritus, intermittent fever, and marked hypercholesterolemia with development of palmar xanthomata. The jaundice was found to be attributable to vanishing bile duct syndrome (VBDS). The extent of hepatic dysfunction precluded appropriate treatment of the lymphoma with chemotherapy, and the boy died of liver failure. In the differential diagnosis of jaundice in children with hodgkin disease, VBDS should be considered.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
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