Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome.
(17/242)
Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family. Eight additional mutations were identified in unrelated patients. Expression of two of these mutations in Xenopus oocytes revealed loss of function and a dominant negative effect in Kir2.1 current as assayed by voltage-clamp. We conclude that mutations in Kir2.1 cause Andersen's syndrome. These findings suggest that Kir2.1 plays an important role in developmental signaling in addition to its previously recognized function in controlling cell excitability in skeletal muscle and heart. (+info)
Localisation of a gene for an autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia, and distinctive facies to chromosome 15q26.
(18/242)
BACKGROUND: We have previously described an autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia (MED), and distinctive facies in a large, extended Omani family. The MED observed seems to be part of a larger malformation syndrome, since both craniofacial and central nervous system changes were present in the family. We performed a whole genome scan in this family in order to identify the gene locus for this malformation syndrome. METHODS AND RESULTS: Using homozygosity mapping, we show linkage to the telomeric region of the long arm of chromosome 15. The position of both the disease gene and the principal glycoprotein, chondroitin sulphate proteoglycan (aggrecan, AGC1) on chromosome 15q26, suggested that the aggrecan gene is a candidate for the disease in this family. However, three of the four affected children were heterozygous for a polymorphism at position 831 of the coding sequence of AGC1, providing strong evidence against its involvement. CONCLUSION: We have identified a gene locus for a recessive syndrome of macrocephaly, MED, and distinctive facies in a large Omani family. Aggrecan located on chromosome 15q26, within the critical region determined for this syndrome in this family, was excluded as a candidate gene. (+info)
A longitudinal evaluation of craniofacial growth in a patient with Kabuki make-up syndrome: a case report.
(19/242)
The purpose of this investigation was to evaluate the craniofacial growth of a patient diagnosed with Kabuki make-up syndrome (KMS). Craniofacial growth was assessed by analysing lateral cephalometric radiographs with an interval of 12-15 months. They were taken from 6 years 9 months to 14 years 2 months. Angular and linear measurement analyses of the craniofacial complex showed a hypoplastic maxilla and a constricted maxillary basal arch width. The mandibular size was relatively large and had started to increase from 13 years 4 months. This resulted in a prognathic face caused by forward growth of the mandible and insufficient growth of the maxilla. The skeletal pattern was Class III. Open bite morphology with a steep mandibular plane (SN-MP), a relatively short ramus, and a large gonial angle were also observed. In this subject, the facial dysmorphism found in the maxilla and mandible may have been influenced by several factors. Connective tissue disorder, macroglossia, lower tongue posture, and tongue thrust swallowing have been identified as possible aetiological factors that may determine dysmorphism in the craniofacial complex in this KMS patient. (+info)
Congenital disorder of glycosylation type Ia (CDG-Ia): phenotypic spectrum of the R141H/F119L genotype.
(20/242)
AIMS: To delineate common and variable features and outcome of children with congenital disorder of glycosylation type Ia (CDG-Ia) caused by the frequent R141H/F119L PMM2 genotype. METHODS: Clinical data on 25 patients (mean age 7.6 years, range 0-19) were analysed. RESULTS: All patients had an early presentation with severe feeding problems and failure to thrive, hypotonia, hepatic dysfunction, inverted nipples, and abnormal subcutaneous fat pads. Eighteen patients were hospitalised in the neonatal period. Developmental delay was obvious before age 6 months. During the first seven months mean standard deviation score (SDS) for weight and length decreased 2.7 (SD = 2) and 2.4 (SD = 2), respectively. Mental retardation, ataxia, muscular atrophy, and febrile seizures were consistent features after infancy. Variable features included pericardial effusions, afebrile seizures, and stroke like episodes. Computed tomography/magnetic resonance imaging of the brain was normal in two patients examined before 4 months of age, but 18 children examined after 3 months of age had cerebellar atrophy, and 10 children also had supratentorial atrophy. Subsequent imaging showed progression of the cerebellar and supratentorial atrophy in eight and four of 10 children, respectively. Mean head circumference SDS declined from zero to -1.9 SD from age 3 months to 5 years. Motor ability ranged from none to walking with a rolator, and vocabulary ranged from none to comprehensible speech. The overall mortality ascribed to CDG-Ia was 18%. CONCLUSION: Patients with the R141H/F119L genotype have an early uniform presentation including severe failure to thrive, but their functional outcome is variable. This genotype may well cause clinical manifestations in the severe end of the spectrum of CDG-Ia. (+info)
Why do some people look older than they should?
(21/242)
BACKGROUND: As a component of studies on biological age, the age of subjects from their appearance (perceived age) was estimated. OBJECTIVE: To determine the factors associated with looking older. METHODS: Cross sectional study of London civil servants (318 men, 129 women) in the Department of the Environment study. Perceived age was recorded by an observer and the difference between this age and chronological age was analysed according to 20 different variables. RESULTS: Men had an average perceived age of 0.37 years older than their actual age and women a perceived age of 0.54 years younger. In men, looking older was related to greying of the hair, grade of arcus senilis, and grade of baldness. Less expected, looking older was positively related to total serum cholesterol (p=0.03) and blood haemoglobin (p<0.01). In women, looking older was related to greying of the hair, positively to blood erythrocyte sedimentation rate (ESR), and negatively to serum bilirubin (p=0.01). Looking older was not related to alcohol consumption, employment grade, serum high density lipoprotein cholesterol, glucose, albumin, and calcium in either sex. CONCLUSION: The relationships between looking older and total cholesterol and haemoglobin in men and ESR and bilirubin in women, require further investigation. (+info)
Thalassemias and their dental implications.
(22/242)
Thalassemias constitute a form of anemia that pose clear problems in relation to dental treatment. Dental professionals must be aware of the treatment adaptations required in patients with severe forms of beta-thalassemia. Until medical research is able to afford a definitive solution to these diseases (thereby greatly simplifying the dental management of such patients), effort will continue to center on the improvement of available therapeutic modalities, with the aim of obtaining effective and inexpensive oral chelators and drugs that either individually or in combination allow increases in fetal hemoglobin levels. Undoubtedly, the use of such measures together with serial blood transfusions has made it possible for an ever increasing number of patients with beta-thalassemia to reach adult age, where the provision of integral rather than merely palliative dental treatment must be seriously considered. At present, the clinical orofacial manifestations caused by the erythroid mass expanding the facial bones - resulting in dental malocclusions and protrusions tend to be less intense as a result of early medical treatment. In the future, gene therapy may be expected to allow a normal facial appearance thanks to complete healing of the patient. (+info)
Genomic organisation of the approximately 1.5 Mb Smith-Magenis syndrome critical interval: transcription map, genomic contig, and candidate gene analysis.
(23/242)
Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome associated with an interstitial deletion of chromosome 17 involving band p11.2. SMS is hypothesised to be a contiguous gene syndrome in which the phenotype arises from the haploinsufficiency of multiple, functionally-unrelated genes in close physical proximity, although the true molecular basis of SMS is not yet known. In this study, we have generated the first overlapping and contiguous transcription map of the SMS critical interval, linking the proximal 17p11.2 region near the SMS-REPM and the distal region near D17S740 in a minimum tiling path of 16 BACs and two PACs. Additional clones provide greater coverage throughout the critical region. Not including the repetitive sequences that flank the critical interval, the map is comprised of 13 known genes, 14 ESTs, and six genomic markers, and is a synthesis of Southern hybridisation and polymerase chain reaction data from gene and marker localisation to BACs and PACs and database sequence analysis from the human genome project high-throughput draft sequence. In order to identify possible candidate genes, we performed sequence analysis and determined the tissue expression pattern analysis of 10 novel ESTs that are deleted in all SMS patients. We also present a detailed review of six promising candidate genes that map to the SMS critical region. (+info)
Cephalometric measurements and facial deformities in subjects with beta-thalassaemia major.
(24/242)
This study was performed to identify cephalometric and facial features of patients with beta-thalassaemia major. A total of 54 thalassaemic subjects were examined for craniofacial deformities, including 37 patients (24 males and 13 females, aged 5-16 years) who had lateral cephalometric radiographs. The thalassaemic groups were compared with a normal control group matched for sex and dental age, using a t-test. All thalassaemic patients had a Class II skeletal base relationship. The average ANB angle was significantly larger than the controls in dental stages 2 and 3 (P < 0.05). Mandibular base length (Ar-Gn) was significantly less in thalassaemic patients than in controls, with the greatest differences (P < 0.001) found in the younger age group. The maxilla was of normal length (PNS-ANS, Ptm'-ANS') and appeared prominent (3.3 mm in males and 5.1 mm in females) due to a reduced cranial base length (Ar'-S') and a short mandible (Ar'-P'). Vertically, thalassaemic patients showed a significantly increased maxillary/mandibular planes angle in all groups, with differences ranging between 6.19 and 12.55 degrees (P < 0.001). Thalassaemic patients also showed a reduced posterior facial height (S-Go, Ar-Go) and increased anterior facial proportions. Of the 54 thalassaemic patients examined, 17 per cent had severe facial disfigurements (grade 3). (+info)