RESUMO
INTRODUCTION: Information on achieving presymptomatic diagnosis of spinocerebellar ataxia (SCA) is limited. The advent of molecular diagnosis makes it possible to identify the carriers of different diseases and has also introduced the prospect of detecting diseases even before their onset. This has drawn attention to the ethical implications that must be considered in these subjects with a view to preserving their physical and psychological well-being. DEVELOPMENT: SCA is composed of a group of neurodegenerative disorders with autosomal dominant inheritance. Only a few publications have described the genetic counselling processes and guidelines to be followed during the process of presymptomatic diagnosis (PSD). The size of the multidisciplinary teams, their areas of expertise, and the number of counselling sessions are different for each of the studies analysed here. However, the basis of presymptomatic diagnosis originates in common guidelines to which members of our team have contributed recently. CONCLUSION: Presymptomatic diagnosis should be performed according to guidelines that safeguard the subjects' welfare. The diagnostic process is only recommended for patients over 18 years old with symptoms suggesting SCA, and a minimum risk of 50%. Genetic counselling programmes must be available in all centres that offer presymptomatic diagnosis of SCA.
Assuntos
Doenças Assintomáticas , Aconselhamento Genético/ética , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , HumanosRESUMO
The appearance of untreated severe hydrocephalus with long-term survival is infrequent; here we report a case with these characteristics, mild neurological alterations and kidney and skeletal anomalies. A female patient showed severe hydrocephalus (initially mistaken with hydranencephaly) at 4 years old and left kidney ectopia (initially mistaken with renal agenesis); however, she was derived to the neurology service until she was 12 years old, when she began to present migraine and seizures. At 13 years old the patient was diagnosed with arrested hydrocephalus secondary to aqueduct stenosis, and the seizures worsen thereafter from atonic seizures to complex partial seizures (at 14 years old), presenting generalized seizures at 15 years old. At 17 years old, the seizures were more frequent despite the anticonvulsant treatment and also presented automations, she was also diagnosed with genu recurvatinn and scoliosis. The seizures finally diminished and partially controlled at 19 years old. Despite a cerebral mantle < 2.0 cm at the computer tomography, the patient always presented a satisfactory intellectual development. In this case, the relatively good and long evolution of the severe hydrocephalus is probably related with the late-onset of the disease that permitted a better development of the brain; however, the worsening of the seizures after the hydrocephalus arrested, suggests that arrest is not necessarily associated with a compensation and better evolution of the disease, at least at the beginning of the process. The presence of kidney ectopia and skeletal alterations did not associate with a known genetic disease, however a possible inheritance mechanism is not discarded.
Assuntos
Epilepsia Generalizada/diagnóstico , Hidrocefalia/diagnóstico , Inteligência , Rim/anormalidades , Doenças Musculoesqueléticas/diagnóstico , Adolescente , Encéfalo/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Epilepsia Generalizada/genética , Feminino , Humanos , Hidrocefalia/genética , Inteligência/genética , Estudos Longitudinais , Imageamento por Ressonância Magnética , Doenças Musculoesqueléticas/genética , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
A three-dimensional (3D) scaffolding system for chondrocytes culture has been produced by agglomeration of cells and gelatin microparticles with a mild centrifuging process. The diameter of the microparticles, around 10 µ, was selected to be in the order of magnitude of the chondrocytes. No gel was used to stabilize the construct that maintained consistency just because of cell and extracellular matrix (ECM) adhesion to the substrate. In one series of samples the microparticles were charged with transforming growth factor, TGF-ß1. The kinetics of growth factor delivery was assessed. The initial delivery was approximately 48 % of the total amount delivered up to day 14. Chondrocytes that had been previously expanded in monolayer culture, and thus dedifferentiated, adopted in this 3D environment a round morphology, both with presence or absence of growth factor delivery, with production of ECM that intermingles with gelatin particles. The pellet was stable from the first day of culture. Cell viability was assessed by MTS assay, showing higher absorption values in the cell/unloaded gelatin microparticle pellets than in cell pellets up to day 7. Nevertheless the absorption drops in the following culture times. On the contrary the cell viability of cell/TGF-ß1 loaded gelatin microparticle pellets was constant during the 21 days of culture. The formation of actin stress fibres in the cytoskeleton and type I collagen expression was significantly reduced in both cell/gelatin microparticle pellets (with and without TGF-ß1) with respect to cell pellet controls. Total type II collagen and sulphated glycosaminoglycans quantification show an enhancement of the production of ECM when TGF-ß1 is delivered, as expected because this growth factor stimulate the chondrocyte proliferation and improve the functionality of the tissue.
Assuntos
Cartilagem , Gelatina/química , Engenharia Tecidual , Alicerces Teciduais/química , Cápsulas/química , Cápsulas/farmacologia , Cartilagem/citologia , Cartilagem/efeitos dos fármacos , Cartilagem/fisiologia , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Precipitação Química , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/fisiologia , Gelatina/farmacologia , Humanos , Microesferas , Tamanho da Partícula , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos , Fator de Crescimento Transformador beta1/administração & dosagem , Fator de Crescimento Transformador beta1/farmacocinética , Água/metabolismoRESUMO
Gingival fibromatosis can be present as an isolated form or be part of a genetic disease. The Zimmermann-Laband syndrome (ZLS) is a rare disorder inherited as an autosomal dominant fashion, clinically characterized by gingival fibromatosis, bulbous soft nose, thick floppy ears, nail dysplasia, joint hyperextensibility, hepatosplenomegaly, skeletal anomalies and occasional mental retardation. We studied a girl aged five years with clinical and radiological features of the ZLS, additionally she presented deafness not previously described in the ZLS, as only partial hearing loss was reported in some patients. The father presented some facial features suggestive of ZLS, nevertheless he did not have gingival fibromatosis or hypertrichosis. We suggest that this case supports that ZLS can be part a contiguous genes syndrome or be consequence ofa gene mutation with wide variable expression. The present report supports that ZLS has a wide clinical spectrum.
Assuntos
Anormalidades Múltiplas , Aberrações Cromossômicas , Anormalidades Craniofaciais , Fibromatose Gengival , Deformidades Congênitas da Mão , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Criança , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/genética , Surdez/diagnóstico , Surdez/genética , Diagnóstico Diferencial , Feminino , Fibromatose Gengival/diagnóstico , Fibromatose Gengival/genética , Expressão Gênica/genética , Genes Dominantes/genética , Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/genética , Humanos , FenótipoRESUMO
Tendon and ligament shows extremely limited endogenous regenerative capacity. Current treatments are based on the replacement and or augmentation of the injured tissue but the repaired tissue rarely achieve functionality equal to that of the preinjured tissue. To address this challenge, tissue engineering has emerged as a promising strategy. This study develops a regenerative and resorbable hybrid construct for tendon and ligament engineering. The construct is made up by a hollow poly-lactic acid braid with embedded microspheres carrying cells and an anti-adherent coating, with all the parts being made of biodegradable materials. This assembly intends to regenerate the tissue starting from the interior of the construct towards outside while it degrades. Fibroblasts cultured on poly lactic acid and hyaluronic acid microspheres for 6 h were injected into the hollow braid and the construct was cultured for 14 days. The cells thus transported into the lumen of the construct were able to migrate and adhere to the braid fibers naturally, leading to a homogeneous proliferation inside the braid. Moreover, no cells were found on the outer surface of the coating. Altogether, this study demonstrated that PLA/HA hybrid construct could be a promising material for tendon and ligament repair.
Assuntos
Fibroblastos/metabolismo , Ácido Hialurônico/química , Ligamentos/metabolismo , Poliésteres/química , Tendões/metabolismo , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Linhagem Celular , Fibroblastos/citologia , Ligamentos/citologia , Camundongos , Tendões/citologiaRESUMO
A series of polymeric biomaterials including poly (methyl acrylate) (PMA), chitosan (CHT), poly(ethyl acrylate) (PEA), poly(hydroxyethyl acrylate) (PHEA), and a series of random copolymers containing ethyl acrylate and hydroxyethyl acrylate monomeric units were tested in vitro as culture substrates and compared for their impact on the proliferation and expansion of Schwann cells (SCs). Immunocytochemical staining assay and scanning electron microscopy techniques were applied to perform a quantitative analysis to determine the correct maintenance of the cultured glial cells on the different biomaterials. The results strongly suggest that cell attachment and proliferation is influenced by the substrate's surface chemistry, and that hydrophobic biomaterials based on PMA, PEA, and the copolymers PEA and PHEA in a narrow composition window are suitable substrates to promote cell attachment and proliferation of SCs in vitro.
Assuntos
Células de Schwann/citologia , Animais , Adesão Celular , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Ratos , Ratos Wistar , Células de Schwann/ultraestrutura , Especificidade por Substrato , Tensão Superficial , Água/metabolismoRESUMO
We describe two unrelated patients and the mother of one of them showing clinical and radiological features as those previously described in the spondyloepiphyseal dysplasia-brachydactyly and distinctive speech (SED-BDS, also named Fantasy Island syndrome or Tattoo dysplasia) clinically characterized by short stature with acral shortness, distinctive face, mild blepharophimosis, upslanted palpebral fissures, abundant eyebrows and eyelashes, thick and abundant hair and coarse voice; and radiologically by brachymetacarpalia, brachymetatarsalia and brachyphalangia of all fingers and toes, short and broad long bones with normal morphology and small pelvis. The clinical and radiological features present in mother and son suggest a probable autosomal dominant mode of inheritance and variable expressivity.
Assuntos
Anormalidades Múltiplas , Dedos/anormalidades , Distúrbios da Fala , Dedos do Pé/anormalidades , Anormalidades Múltiplas/genética , Adolescente , Adulto , Pré-Escolar , Nanismo/genética , Fácies , Feminino , Doenças Genéticas Ligadas ao Cromossomo X , Cabelo , Humanos , Masculino , Distúrbios da Fala/genética , SíndromeRESUMO
Zimmermann-Laband syndrome (ZLS) is an autosomal dominant disorder characterized by gingival fibromatosis, absent or dysplastic distal phalanges, vertebral defects, hepatosplenomegaly, hypertrichosis and sometimes mental retardation. We describe two unrelated patients, a girl aged 9 years and a boy 11 months whose clinical and radiological findings permit us to diagnose the ZLS. Body overgrowth, present in both patients, was identified as a main clinical feature not previously reported as well as the presence in neuroimaging studies of a cavernous hemangioma on the frontal and the left cerebellar regions in the boy. The girl also presented important radiological characteristics such as broad medulary canals and metaphyses of long bones, thin cortices, broad ribs, accelerated skeletal maturation as well as high intelligence level. A wide clinical spectrum in ZLS is also considered.
Assuntos
Transtornos Cromossômicos/genética , Fibromatose Gengival/complicações , Fibromatose Gengival/genética , Hipertricose/complicações , Hipertricose/genética , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Convulsões/complicações , Convulsões/genética , Criança , Feminino , Humanos , SíndromeRESUMO
A 10-month-old girl with psychomotor retardation, microcephaly, bilateral microphthalmia, and postaxial polydactyly of the feet was karyotyped using banding techniques and (single or dual color) fluorescent in situ hybridization (FISH) with four probes: D13Z1/D21Z1, pancentromeric, pantelomeric, and a mix of 13q subtelomeric and 13/21 alphoid repeats. She was found to have a 47-chromosome karyotype in which a normal 13 was replaced by two stable markers derived from a breakpoint at 13q21.1, namely a del(13)(q21.1) and an isofragment(13) (qter-->q21.1::q21.1-->qter). The latter had a single C-negative but Cd-positive primary constriction at 13q32 which, however, was not obvious in about 12% of the cells. FISH studies showed that the small 13q- had the 13-centromere and a 13q telomere (as shown for a specific 13q subtelomeric signal) onto the broken end whereas the isofragment lacked alphoid signals but had 13q subtelomeric sequences on both ends. Parental karyotypes were normal. The patient's rearrangement represents the eighth chromosome-13-derived marker with a nonalphoid neocentromere located at 13q. All in all, such neocentromeres have been described in 29 markers derived from chromosomes 2, 3, 8-11, 13-15, 20, and Y, and plausibly result from the epigenetic activation of a latent centromere, which may even be a telomere with neocentric activity. The 13q telomere found in the del(13q) was probably captured from the homologous chromosome.
Assuntos
Centrômero/genética , Quebra Cromossômica , Cromossomos Humanos Par 13 , Marcadores Genéticos , Anormalidades Múltiplas , Encéfalo/anormalidades , Bandeamento Cromossômico , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , TelômeroRESUMO
The hereditary paraplegias are a heterogeneous group of genetic disorders characterized mainly by spastic paraparesis, which may be found as an isolated "pure form" known as Strümpell-Lorrain syndrome, or associated with a wide group of other manifestations [Harding, 1990; McKusick, 1994]. We studied two unrelated families, one with five members and the other with 11 members (over four generations), affected by a syndrome of late onset spastic paraparesis and dementia. Both pedigrees suggest an autosomal dominant pattern of inheritance. However, this cannot be concluded definitely because male-to-male transmission was not seen. Since this disorder has a late age of onset, we still do not know who will become affected in the second, third, and fourth generations. The association of late onset spastic paraparesis and dementia, without other pathological findings, has not been reported and probably represents a distinct entity.
Assuntos
Demência/genética , Paraparesia Espástica Tropical/genética , Paraplegia/genética , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
The Pitt-Rogers-Danks syndrome is an entity characterized by proportionate short stature and low weight of prenatal onset, moderate to severe mental retardation, seizures, and typical facial changes including microcephaly, telecanthus, upward or downward slanting palpebral fissures, prominent eyes, ocular abnormalities, hypoplastic maxilla, short philtrum, and large mouth. This is the seventh reported case, and the first one in which the patient also presents with optic atrophy. Autosomal recessive inheritance has been proposed until now, however, the increased paternal age seen in this case is suggestive of a possible autosomal dominant de novo mutation.
Assuntos
Anormalidades Múltiplas/genética , Face/anormalidades , Transtornos do Crescimento/genética , Deficiência Intelectual/genética , Pré-Escolar , Genes Dominantes , Humanos , Masculino , Mutação , Atrofia Óptica/genética , SíndromeRESUMO
The hypertrichosis and osteochondrodysplasia syndrome is a rare entity with clinical findings including macrosomia at birth cardiomegaly. Autosomal recessive inheritance is presumed based on the report of two affected sibs born to healthy parents. Here we report on four new patients with their follow-up data, as well as on one of the four cases from the original report. Comparison of all eight cases indicates that they share 50% of clinical and radiological changes. This report contributes to the further delineation of this newly recognized syndrome.
Assuntos
Anormalidades Múltiplas/genética , Cardiomegalia/congênito , Hipertricose/congênito , Osteocondrodisplasias/congênito , Adolescente , Cardiomegalia/diagnóstico , Cardiomegalia/genética , Criança , Pré-Escolar , Feminino , Humanos , Hipertricose/diagnóstico , Hipertricose/genética , Masculino , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , Fenótipo , Radiografia , Síndrome , Raios XRESUMO
A male clinically affected by the OEIS complex was studied. His mother, aged 30 years, has an affective disorder and ingested 30 mg of Diazepam daily, from 3 months previous to the gestation and during the entire pregnancy. At birth, a closure during the entire pregnancy. At birth, a closure defect of the anterior abdominal wall, exstrophy of hemibladders, exposure of intestinal epithelium, abnormal pelvis, imperforate anus, and bifid penis were noted. Birth weight was 3600 g and other measurements were not recorded. Colostomy was performed in the postnatal period followed by partial closure of the abdominal wall defect, and iliac osteotomies. At six years, 6 months of age, physical examination showed somatometric measurements around the third percentile (height 109 cm, weight 17 kg, cephalic circumference 48.5 cm). Clinically he presented mild mental retardation, functional colostomy, incomplete closure of the vesical exstrophy, imperforate anus, bifid penis and scrotum, descended testes, diastasis of pubis, lumbosacral scoliosis and shortening of the left leg (clinical photograph of the external features is not included as we were not able to obtain authorization to do so). Radiological studies (Figure 1) revealed wide separation of the ischiopubic bones; lumbosacral region with rotoscoliosis, platyspondyly and dysraphism; left coxa valga, and right coxa vara. The abdominal ultrasonographic studies showed unilateral renal agenesis (left). Chromosomal analysis (GTG bands) in peripheral blood lymphocyte cultures demonstrated a normal 46,XY constitution. Exposure to other substances, particularly alcohol, were excluded with the study of the mother's medical history and through information obtained from relatives.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anormalidades Induzidas por Medicamentos , Anormalidades Múltiplas/induzido quimicamente , Diazepam/efeitos adversos , Anormalidades Induzidas por Medicamentos/diagnóstico por imagem , Anormalidades Múltiplas/diagnóstico por imagem , Adulto , Anus Imperfurado/induzido quimicamente , Extrofia Vesical/induzido quimicamente , Feminino , Hérnia Umbilical/induzido quimicamente , Humanos , Recém-Nascido , Masculino , Gravidez , Radiografia , Disrafismo Espinal/induzido quimicamenteRESUMO
The fragile X (fra-X) syndrome is the most frequent form of inherited mental retardation. Facial dysmorphism, macroorchidism and a folate-sensitive fragile site on Xq27.3 are commonly associated features. The gene causing this disorder, designated as FMR1, is X-linked and shows an unusual inheritance mode. A multistep amplification of the CGG repeats at the 5' end of the FMR1 gene has been recently identified as the cause of the fra-X syndrome. Different numbers of repeats define three gene forms (normal, premutated and mutated), whose ranges show little variation in the populations studied so far. We analyzed 18 Mexican individuals with the fra-X syndrome, 40 of their relatives (first and second degree), and 76 healthy individuals without antecedents of mental retardation. Southern blot and PCR permitted the assessment of the number of CGG repeats and the methylation state of the FMR1 gene for the normal, premutated, and mutated alleles. The results showed no statistical differences when compared with those from other populations. No cytogenetic expression of the Xq27.3 fragile site in 50% of the affected males and in all the affected and carrier females was observed. This finding emphasizes the necessity of a molecular analysis in fra-X cases and their relatives in order to provide a more adequate genetic counseling.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Genética Populacional , Sequência de Bases , Estudos de Casos e Controles , Feminino , Humanos , Masculino , México , Dados de Sequência MolecularRESUMO
We describe four members of a family in which the clinical and radiological findings lead to consider the diagnosis of osteopoikilosis. The symptoms in all affected members were only those referred to as typical radiological features; these features became more extensive with older age. None of the subjects showed the skin lesions reported in the Buschke-Ollendorff syndrome. The importance of a suitable differential diagnosis is emphasized in order to avoid dangerous and unnecessary treatments.
Assuntos
Aberrações Cromossômicas/genética , Genes Dominantes/genética , Osteopecilose/genética , Adulto , Osso e Ossos/diagnóstico por imagem , Transtornos Cromossômicos , Feminino , Triagem de Portadores Genéticos , Humanos , Osteopecilose/diagnóstico por imagem , Linhagem , Fenótipo , RadiografiaRESUMO
The Aarskog syndrome is a true MCA syndrome with X-linked recessive inheritance. The clinical phenotype, and its evolution with age, have been well documented in the past. Few data are reported on the radiological skeletal changes and findings. The purpose of the present paper is to describe the clinical and radiological findings in two brothers with Aarskog syndrome and to further delineate the radiological characteristics of this condition. The main findings are asynchronic and delayed bone age, shortened long tubular bones with wide metaphyses, brachyphalangy, hypoplasia of the middle phalanges of the fifth fingers, short and broad first metacarpals and metatarsals and pelvic hypoplasia.
Assuntos
Anormalidades Múltiplas/genética , Ossos Faciais/anormalidades , Dedos/anormalidades , Genitália Masculina/anormalidades , Aberrações dos Cromossomos Sexuais/genética , Crânio/anormalidades , Cromossomo X , Anormalidades Múltiplas/diagnóstico por imagem , Determinação da Idade pelo Esqueleto , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/genética , Osso e Ossos/diagnóstico por imagem , Pré-Escolar , Nanismo/diagnóstico por imagem , Nanismo/genética , Ossos Faciais/diagnóstico por imagem , Dedos/diagnóstico por imagem , Genes Recessivos/genética , Genitália Masculina/diagnóstico por imagem , Humanos , Masculino , Crânio/diagnóstico por imagem , SíndromeRESUMO
Complete achromatopsia associated with skeletal anomalies: a new autosomal recessive syndrome: Achromatopsia or rod monochromatism is the complete absence of color discrimination, with an estimated frequency of 1 in 100,000. To date the McKusick Catalogue includes more than 10 entities related to Achromatopsia. This paper describes four Mexican sibs with a stationary rod monochromatism, associated with long fingers and toes, hypothenar and thenar hypoplasia and pes planus, suggesting a new genetic entity probably inherited in an autosomal recessive mode.
Assuntos
Osso e Ossos/anormalidades , Aberrações Cromossômicas , Defeitos da Visão Cromática/genética , Genes Recessivos/genética , Adolescente , Criança , Defeitos da Visão Cromática/fisiopatologia , Feminino , Humanos , Masculino , Células Fotorreceptoras Retinianas Bastonetes/fisiopatologia , SíndromeRESUMO
A mother and a daughter affected with multiple trichoepithelioma were studied. The age of onset of the symptomatology in both was 7-years-old, the daughter being more severely affected than the mother at this age. This early age of onset is an exceptional observation which could be explained by maternal imprinting.
Assuntos
Aberrações Cromossômicas/genética , Neoplasias Faciais/genética , Genes Dominantes/genética , Neoplasia de Células Basais/genética , Neoplasias Primárias Múltiplas/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Cutâneas/genética , Adulto , Criança , Transtornos Cromossômicos , Feminino , Expressão Gênica/fisiologia , Humanos , FenótipoRESUMO
The Floating-Harbor syndrome (FHS) is clinically characterized by short stature, retarded speech development, delayed bone age, typical facies, bulbous nose, wide columella, thin lips. Four cases with celiac disease have been described previously. In two other cases, autosomal dominant inheritance has been suggested. We describe a boy aged 2 years 11 months with clinical features of FHS and celiac disease. His mother also presents minor phenotypical characteristics, suggesting that the present observation corresponds to a variant example of familial FHS.
Assuntos
Doenças do Desenvolvimento Ósseo/genética , Doença Celíaca/genética , Anormalidades Craniofaciais/genética , Nanismo/genética , Variação Genética , Transtornos do Desenvolvimento da Linguagem/genética , Determinação da Idade pelo Esqueleto , Doenças do Desenvolvimento Ósseo/diagnóstico , Doença Celíaca/diagnóstico , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 22 , Anormalidades Craniofaciais/diagnóstico , Nanismo/diagnóstico , Fácies , Triagem de Portadores Genéticos , Humanos , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Masculino , SíndromeRESUMO
A 15 year old girl with the Myhre type growth-mental retardation syndrome is described. This is the first female case reported in the literature. The inheritance pattern of this condition is not clear.