Myelomeningocele associated with split cord malformation type I -three case reports-.

Three neonates presented with split cord malformation (SCM) associated with myelomeningocele (MMC), complicated with various coexisting anomalies. All patients were female and classified as SCM type I. All patients had a syrinx located rostral to the SCM. One patient had hydrocephalus and Chiari malformation causing serious respiratory problems. Two patients had partial hypertrichosis located close to the MMC, suggesting association with SCM. One patient had sacral hypoplasty and right kidney agenesis, suggesting that some embryologic errors may affect not only neural but also mesodermal development. All patients underwent surgical treatment for SCM after detailed evaluation and management of concomitant anomalies, and developed no new neurological deficits. Delayed surgery is an alternative treatment strategy for SCM in patients with both SCM and MMC with similar complications.

Concurrent Ewing sarcoma family of tumors and fibrous dysplasia: possible diagnostic pitfall.

We present 2 patients with synchronous Ewing sarcoma family of tumors (ESFTs) and fibro-osseous lesion in the independent sites, possibly causing misjudgment in staging. Each patient showed another activity apart from the primary ESFT lesion on gallium and/or thallium scintigraphy at initial presentation. Of note is that such lesions showed no obvious radiologic change even though the primary ESFT lesions were mildly shrunken during chemotherapy. The biopsies confirmed fibrous dysplasia (FD) in the first patient and fibro-osseous lesion, possibly FD in the second patient. As far as we know, concurrent ESFT and FD in independent sites have never been described. However, this unusual combination emphasized the possibility of concurrent FD mimicking metastasis in a patient with malignancy and the view that exploratory biopsy should be performed in a critical case to make staging. Further investigation will be required about whether the co-occurrence of ESFD and FD in our patients is coincidence or genetic linkage.

Prevalence of obesity, hyperlipemia and insulin resistance in children with suprasellar brain tumors.

Weight gain is a common sequela of suprasellar tumors, referred to as hypothalamic obesity. We undertook an evaluation of obesity and metabolic aberrations among patients treated at our institute. During the 12 mo from Apr. 2005, 23 patients (10 males and 13 females) with remitted suprasellar tumors attended our clinic: 10 patients with craniopharyngioma, 7 with germinoma, 4 with optic nerve glioma and others. Of these, 12 patients (52%) were found to have obesity on the basis of percent overweight and/or percent body fat. Elevated cholesterol and/or triglyceride (TG) was found in 9 patients (39%), and insulin resistance was suspected in 7 patients (30%). Three patients exhibited strikingly elevated postprandial TG levels. All 6 patients with the growth without GH phenomenon had at least one metabolic aberration. In conclusion, the prevalence of hypothalamic obesity was nearly half in our series, and hyperlipemia and insulin resistance were also frequently found. The increased risk for metabolic aberration in growth without GH patients was suggested.

Trigonocephaly in a boy with paternally inherited deletion 22q11.2 syndrome.

Deletion 22q11.2 syndrome is a well-known contiguous gene syndrome, for which the list of findings is extensive and varies from patient to patient. We encountered a unique patient who had a familial 3-Mb deletion 22q11.2 associated with trigonocephaly derived from craniosynostosis of the metopic suture. Almost all the symptoms of the patient, including polymicrogyria, microcephaly, facial abnormalities, internal anomalies, seizures, and mental retardation, were compatible with deletion 22q11.2 syndrome, except for synostosis of the metopic suture. This is the first report of a relationship between deletion 22q11.2 syndrome and trigonocephaly. Craniosynostosis of the metopic suture might be a minor complication of deletion 22q11.2, although coincidental occurrence cannot be ruled out.

Phenotypic diversity in patients with craniosynostoses unrelated to Apert syndrome: the role of fibroblast growth factor receptor gene mutations.

OBJECT: The goal of this study was to elucidate the genotype-phenotype relationship in syndromic craniosynostoses by analyzing the mutations of the fibroblast growth factor receptor (FGFR) gene and its clinical manifestations in patients, particularly those in atypical cases. METHODS: Twenty patients with craniosynostoses unrelated to Apert syndrome were enrolled in this study. The phenotypes indicated the following syndromes: 12 patients with unrelated Crouzon syndrome, including nine sporadic and three familial cases; two with sporadic Pfeiffer syndrome; and one with Antley-Bixler syndrome. The Crouzon phenotype was subdivided into three clinical forms: regular, top, and bottom ones. Two patients who demonstrated craniofacial anomalies and bilateral elbow joint contractures were categorized as having an unspecified craniosynostosis. Three cases of unclassifiable cloverleaf skull malformation were also analyzed. Fourteen mutations of the FGFR2 gene were identified in these patients; seven of the 10 cysteine-related mutations were substitutions of codon 342 in the third immunoglobulin-like domain of this gene. The phenotypes of these seven cases were three of regular Crouzon, two of unspecified craniosynostosis, and one each of top Crouzon and unclassifiable cloverleaf skull malformation. In addition, four of the seven patients were found to have the same genotype (Cys342Arg). The phenotypes of these patients, however, were quite variable, ranging from regular Crouzon to unclassifiable cloverleaf skull malformation. CONCLUSIONS: The phenotypes of patients with craniosynostoses unrelated to Apert syndrome proved quite variable, even in cases in which patients demonstrated the same genotype. In view of the phenotypic diversity evident in cases in which the same mutation in the FGFR2 gene is present, it is possible that other disease-modifying genetic factors exist to control the abnormal gain-of-function that accompanies FGFR signaling.

Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma.

This study concerns the significance of nuclear/cytoplasmic expression of beta-catenin and mutation of the beta-catenin gene in craniopharyngiomas. Fourteen adamantinomatous type and one squamous papillary type craniopharyngiomas were studied. Histologically, 13 of 14 adamantinomatous type craniopharyngiomas showed typical features, ie mixtures of 'palisading cells', 'stellate cells', and 'ghost cells'. In addition, 'whorl-like arrays' of epithelial cells were frequently observed in the areas of stellate cells. On immunohistochemistry, all typical adamantinomatous type craniopharyngiomas showed nuclear/cytoplasmic expression of beta-catenin predominantly in cohesive cells within the whorl-like arrays and in cells transitional towards ghost cells, where immunoreactivity for Ki-67 was almost absent. The cohesive cells in the whorl-like arrays also demonstrated loss of cytokeratin isoform expression. Using direct sequencing of amplified nucleic acids, nine of the 13 typical adamantinomatous type craniopharyngiomas with nuclear beta-catenin accumulation showed heterozygous one-base substitution mutation of the beta-catenin gene. The other unusual adamantinomatous type and squamous papillary type craniopharyngiomas showed no obvious nuclear/cytoplasmic beta-catenin immunoreactivity and no mutation of the beta-catenin gene, suggesting molecular heterogeneity. These findings suggest that the pathogenesis of typical adamantinomatous type craniopharyngioma is associated with abnormalities of Wnt signalling that act as a morphogenetic signal towards whorl-like arrays and ghost cells rather than as simple proliferation stimuli.