1/7. Dual-probe fluorescence in situ hybridization assay for detecting deletions associated with VCFS/digeorge syndrome I and digeorge syndrome II loci.Over 90% of patients with digeorge syndrome (DGS) or velocardiofacial syndrome (VCFS) have a microdeletion at 22q11.2. Given that these deletions are difficult to visualize at the light microscopic level, fluorescence in situ hybridization (FISH) has been instrumental in the diagnosis of this disorder. Deletions on the short arm of chromosome 10 are also associated with a DGS-like phenotype. Since deletions at 22q11.2 and at 10p13p14 result in similar findings, we have developed a dual-probe FISH assay for screening samples referred for DGS or VCFS in the clinical laboratory. This assay includes two test probes for the loci, DGSI at 22q11.2 and DGSII at 10p13p14, and centromeric probes for chromosomes 10 and 22. Of 412 patients tested, 54 were found to be deleted for the DGSI locus on chromosome 22 (13%), and a single patient was found deleted for the DGSII locus on chromosome 10 (0. 24%). The patient with the 10p deletion had facial features consistent with VCFS, plus sensorineural hearing loss, and renal anomalies. cytogenetic analysis showed a large deletion of 10p [46, XX,del(10)(p12.2p14)] and FISH using a 10p telomere region-specific probe confirmed the interstitial nature of the deletion. Analysis for the DGSI and the DGSII loci suggests that the deletion of the DGSII locus on chromosome 10 may be 50 times less frequent than the deletion of DGSI on chromosome 22. The incidence of deletions at 22q11.2 has been estimated to be 1 in 4000 newborns; therefore, the deletion at 10p13p14 may be estimated to occur in 1 in 200,000 live births.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
2/7. Lack of expression of XIST from a small ring X chromosome containing the XIST locus in a girl with short stature, facial dysmorphism and developmental delay.A 46,X,r(X) karyotype was found in a three and a half year old girl with short stature, facial dysmorphism and developmental delay. The clinical findings were consistent with the phenotype described in a limited number of patients with small ring X chromosomes lacking the XIST locus, a critical player in the process of x chromosome inactivation. Surprisingly, in our patient, fluorescent in situ hybridisation demonstrated that the XIST locus was present on the ring X. However, expression studies showed that there was no XIST transcript in peripheral blood cells, suggesting that the ring X had not been inactivated. This was confirmed by the demonstration that both of the patient's alleles for the androgen receptor gene were unmethylated, and that both of the patient's ZXDA alleles were expressed. The active nature of the ring X would presumably result in overexpression of genes that may account for the developmental delay observed for the patient. Using polymorphic markers along the X chromosome, the ring X was determined to be of paternal origin with one breakpoint in the long arm between DXS8037 and XIST and one in the short arm in Xp11.2 between DXS1126 and DXS991. To attempt to determine why the XIST gene failed to be expressed, the promoter region was sequenced and found to have a base change at the same location as a variant previously associated with nonrandom x chromosome inactivation. This mutation was not seen in over one hundred normal X chromosomes examined; however, it was observed in the paternal grandmother who did not show substantial skewing of x chromosome inactivation.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
3/7. Schinzel-Giedion syndrome: a further cause of West syndrome.Schinzel-Giedion syndrome (SGS) is a rare disorder with a likely autosomal recessive pattern of inheritance which is characterized by several facial dysmorphisms, midface hypoplasia, multiple skeletal anomalies including short and sclerotic skull base, short neck, and post-axial polydactyly. Cardiac and urogenital malformations are also present. Thirty-three cases have been described so far. We report on a boy affected by SGS in whom a long-term EEG follow-up showed a progressive deterioration of the background bioelectric activity ending, at the age of 19 months, with a hypsarrhythmic pattern clinically correlated with severe and refractory infantile spasms. EEG deterioration and neuroradiological findings, which showed progressive brain atrophy, confirm the neurodegenerative nature of SGS. We also re-evaluated all the published cases and found that 33% of patients with SGS experienced neonatal seizures and another 25% developed West syndrome in the following months. The seizures appeared extremely refractory to several anticonvulsive treatments. In conclusion, we believe that SGS should be included among the causes of secondary West syndrome.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
4/7. Social response in children with severe cognitive impairments: factors in craniofacial surgery decision-making.BACKGROUND: The controversy over whether certain pediatric craniofacial operations primarily address "functional" versus "aesthetic" goals has fostered tensions among insurance companies, patients and families, and treatment teams. The authors posit that such operations have objectives and outcomes that can be categorized as "functionally aesthetic" and describe the empirical basis for this assertion. Furthermore, the authors apply this concept to the difficult surgical decision-making process associated with treating children with severe cognitive impairments. methods: When patients have severe cognitive impairments, the social benefits of treatment may be less clear than for other patients, increasing the complexity of surgery decision-making. The authors discuss the nature of cognitive impairment, its prevalence in patients with craniofacial anomalies, links between social functioning and both cognitive development and appearance, and the importance of social integration for psychological and cognitive functioning. Special issues involved in working with cognitively impaired children are covered, including parent and patient expectations for surgical outcome and the difficulties involved in pain assessment and control. Potential linkages are described for craniofacial surgery, appearance, social functioning, and cognitive development. CONCLUSIONS: A craniofacial operation directed at reconstruction of a congenital defect in a child should not be dismissed as simply and purely cosmetic. The authors document and outline the potential ethical issues and social and cognitive benefits that should be considered by insurance companies, patients and families, and treatment teams when determining treatment options for cognitively impaired children with craniofacial anomalies.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
5/7. A pharyngeal and ectopic hypophysis in a neonate with craniofacial abnormalities: a case report and review of development and structure.OBJECTIVE: A large excrescence was found bulging from the mucoperiosteum of the nasopharynx in a neonate displaying abnormal craniofacial features. The aim of this study was to determine the nature of this tissue mass. DESIGN: Histological examination of this mass of tissue and the surrounding nasopharyngeal mucosal tissue, as well as tissue located in the sella turcica of the sphenoid bone, were carried out. In addition, tissue in a canal connecting the large mass to the sella turcica was removed for analysis. RESULTS: Nervous elements and adenohypophyseal tissue were histologically identified in the large excrescence, but were separate from adenohypophyseal tissue of the pharyngeal hypophysis. Both structures were located in the mucoperiosteum of the nasopharynx. CONCLUSIONS: The large tissue mass found in the nasopharynx is histologically identical to a sellar hypophyseal gland, but differed from the adjacent pharyngeal hypophysis in histological composition. The mass, although sellar in nature, however, was placed ectopically in the nasopharynx and is hence termed pharyngosellar to indicate its abnormal position, as well as its origin.- - - - - - - - - - ranking = 2keywords = nature (Clic here for more details about this article) |
6/7. genotype-epigenotype-phenotype correlations in females with frontometaphyseal dysplasia.Frontometaphyseal dysplasia (FMD) belongs to a group of overlapping skeletal dysplasias, the common molecular basis of which are mutations of FLNA, the gene encoding filamin A. The nature of the mutation has been considered the major determinant of the phenotype within this group that comprises the otopalatodigital syndromes (OPD1, OPD2) and Melnick-needles syndrome besides FMD. However, to date the molecular pathomechanisms are not well understood. In FMD only few FLNA mutations have been reported which do not cluster in a specific region of the protein. We report on a novel de novo mutation 5182G --> T in exon 31 of the FLNA gene in a girl with manifestations of FMD and OPD1. This mutation is predicted to lead to the exchange of a highly conserved glycine residue at position 1,728 by cysteine (G1728C) in repeat 15 of the filamin A rod domain. In a second family with FMD, we identified a known mutation (S1186L) in a mother and her son. In contrast to most previous reports on manifesting females or carriers of the FLNA-related skeletal dysplasias, the affected females presented here showed only mild to moderate skewing of X-inactivation against the mutant allele. Our data may indicate that in females, genotype-phenotype correlation between certain FLNA mutations and OPD1 and FMD, respectively, is less strict than previously assumed. We propose that X-inactivation is an important epigenetic modifier of the phenotype in females with the FLNA-related skeletal dysplasias.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
7/7. Applications of distraction osteogenesis. Part I.Distraction osteogenesis (DO) of facial bones is a recent development in the treatment of pediatric patients. The use of DO in current clinical practice of pediatric reconstructive surgery is primarily limited to severe deformities of the lower jaw, most of which are congenital in nature. Clinical experience with DO for early facial deformities remains limited, and no authoritative works are currently available to guide clinicians in the techniques or indications for DO of the facial skeleton.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |