RESUMO
Holoprosencephaly (HPE) is a severe brain malformation which results from incomplete cleavage of the forebrain during early embryogenesis. The aetiology of HPE is very heterogeneous. Among the genetic factors, SIX3, which is considered to be the functional orthologue of Drosophila genes sine oculis (so) and optix, has been found to be mutated in the homeodomain, in some patients with HPE (HPE2 on chromosome 2p21). We report a new HPE family, presenting a wide spectrum of clinical features, ranging from cyclopia to hypotelorism, in which a mutation was found for the first time in the SIX domain of SIX3: a GG insertion creates a frameshift leading to a nonsense mutation downstream in the homeodomain region.
Assuntos
Códon sem Sentido/genética , Mutação da Fase de Leitura/genética , Genes Homeobox/genética , Holoprosencefalia/genética , Proteínas de Homeodomínio/genética , Proteínas do Tecido Nervoso/genética , Cromossomos Humanos Par 2/genética , Primers do DNA/química , Proteínas do Olho , Feminino , Holoprosencefalia/complicações , Holoprosencefalia/etiologia , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Proteína Homeobox SIX3RESUMO
Two additional pedigrees with familial recurrence of achondroplasia are described. Genetic risk for children of sibs of affected individuals or premutation carriers seems to be low, but it is advisable to monitor at risk pregnancies by midtrimester ultrasonography to diagnose fetal achondroplasia.
Assuntos
Acondroplasia/genética , Aconselhamento Genético , Adulto , Idoso , Feminino , Triagem de Portadores Genéticos , Humanos , Mutação , Linhagem , Recidiva , Fatores de RiscoRESUMO
We report on two sibs with a multiple congenital anomalies/mental retardation (MCA/MR) syndrome who have a first cousin with Möbius anomaly. This may represent a new MCA/MR syndrome.
Assuntos
Anormalidades Múltiplas/genética , Doenças dos Nervos Cranianos/genética , Deficiência Intelectual/genética , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Síndrome , Polegar/anormalidades , Dedos do Pé/anormalidadesRESUMO
BBB syndrome and G syndrome were originally reported as distinct X-linked disorders. Clinical studies indicated that BBB and G syndromes were likely to represent variant expression of the same disorder, now referred to as "Opitz" GBBB syndrome. Several occurrences of male-to-male transmission in both syndromes led to the hypothesis that GBBB syndrome was a single autosomal dominant, sex influenced disorder, now tentatively mapped to 5p12-13. We report on a large pedigree in which GBBB syndrome appears to cosegregate with a pericentric inversion of the X chromosome inv(X)(p22.3q26). It indicates the possible existence of a true X-linked form of GBBB syndrome, which does not appear phenotypically different from its autosomal counterpart. The gene could map in the vicinity of the breakpoints, in Xp or Xq. The existence of two genes affecting a common pathogenetic pathway could explain the gender-dependent expressivity of GBBB phenotype.
Assuntos
Anormalidades Múltiplas/genética , Cromossomo X , Bandeamento Cromossômico , Feminino , Ligação Genética , Humanos , Cariotipagem , Masculino , Linhagem , SíndromeRESUMO
The name opsismodysplasia is proposed for a new chondrodysplasia, which was studied in three patients. Clinically, the condition is recognized at birth on the basis of shortness, short hands, and facial abnormalities with a short nose and a depressed bridge of nose. The most characteristic radiographic signs are: very retarded bone maturation; marked shortness of the bones of the hands and of the feet with concave metaphyses; and thin, lamellar vertebral bodies. The growth cartilage studied in one case showed a wide hypertrophic area containing thick connective tissue septa, irregular provisional calcification, and vascular invasion. Type I collagen was detected in the hypertrophic area by immunohistochemical and microchemical tests. The transmission of opsismodysplasia is probably autosomal recessive.
Assuntos
Anormalidades Múltiplas/diagnóstico , Encondromatose/congênito , Deformidades Congênitas da Mão , Osteocondrodisplasias/congênito , Coluna Vertebral/anormalidades , Cartilagem/patologia , Encondromatose/diagnóstico , Encondromatose/patologia , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
Holoprosencephaly (HPE) is a developmental defect due to a failure of cleavage of the forebrain. The brain malformations are usually associated with facial anomalies. From a series of 258 HPE records involving at least one affected child, 97 cases in 79 families with nonsyndromic and nonchromosomal HPE were selected. The male:female ratio was 0.87. A high degree of familial aggregation was observed in 23/79 families (29%). A segregation analysis performed in the 79 nuclear families led to the conclusion that the transmission of nonsyndromic HPE is compatible with an autosomal dominant mode of inheritance. Under this hypothesis, the penetrance was estimated as 82% for major types (alobar, semilobar, lobar) and 88% when major and minor types (atypical) were included. The proportion of sporadic cases was estimated to be 68%. This genetic model allows a prediction of the recurrence risk after an isolated case of 13% for major types and 14% when minor types are included.
Assuntos
Doenças em Gêmeos/genética , Holoprosencefalia/genética , Modelos Genéticos , Feminino , Genes Dominantes/genética , Heterozigoto , Humanos , Masculino , Idade Paterna , Linhagem , Penetrância , Fatores Sexuais , Gêmeos Dizigóticos , Gêmeos MonozigóticosRESUMO
The name atelosteogenesis is proposed for a lethal chondrodysplasia characterized by deficient ossification of various bones, notably the humerus, femur, thoracic spine, and hand bones. Clinically, the patients have micromelic dwarfism with incurvated legs, club feet, often dislocation of the elbows, and, rarely, a cleft palate. The most characteristic radiographic signs are incomplete ossification of the vertebral bodies with coronal clefts of the lumbar and hypoplasia of the upper thoracic vertebral bodies, a distal hypoplasia and club shape of the humerus and the femur, and the lack of ossification of single phalanges and metacarpals in most patients. Histologically, there are clusters of chondrocytes surrounded by fibrous capsules and, more frequently, degeneration zones containing degenerated chondrocytes and copious amounts of metachromatic material in the epiphyses and the basal zone of the growth plate.
Assuntos
Anormalidades Múltiplas/patologia , Fêmur/anormalidades , Úmero/anormalidades , Osteocondrodisplasias/patologia , Coluna Vertebral/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Cartilagem/patologia , Feminino , Humanos , Recém-Nascido , Masculino , Osteocondrodisplasias/diagnóstico por imagem , Radiografia , SíndromeRESUMO
Intracerebral cysts and porencephaly or arachnoid cysts are rarely but are repeatedly reported in orofaciodigital (OFD) syndrome type 1. We report on 2 families in which OFD syndrome type 1 was observed with central nervous system (CNS) malformations and 3 sporadic cases of OFD with CNS defects, most likely representing fresh mutations for OFD 1. In one case, vermis hypoplasia was present; in another, periventricular heterotopiae were noted. We review the literature on CNS anomalies in OFD syndromes and stress the difficulties in genetic counseling and functional prognosis for children of OFD 1 female carriers prenatally diagnosed with a malformation of the brain. As for CNS malformations, renal cystic disease is an often overlooked complication specific to OFD 1. In 1 family, cystic medullary disease was noted in OFD 1 carriers, leading 1 patient to dialysis by age 35 years and the other to severe renal insufficiency by age 28 years. Longitudinal follow-up of OFD 1 carriers should be performed, and renal function should be assessed in those with cysts because the functional prognosis of this developmental anomaly may be worse than usually reported in the literature.
Assuntos
Doenças do Sistema Nervoso Central/genética , Falência Renal Crônica/genética , Síndromes Orofaciodigitais/complicações , Doenças do Sistema Nervoso Central/complicações , Feminino , Genes Dominantes/genética , Aconselhamento Genético , Humanos , Falência Renal Crônica/complicações , Imageamento por Ressonância Magnética , Síndromes Orofaciodigitais/diagnóstico por imagem , Síndromes Orofaciodigitais/genética , Prognóstico , UltrassonografiaRESUMO
Esterase D (ESD) gene dosage studies were performed on amniotic cells from a fetus at risk for del 13q14. The mother was a balanced carrier of an insertion in chromosome #20: 46,XXins(20;13)(p12;q1307q14.3). She had already given birth to a monosomic child with retinoblastoma (Rb) and to a phenotypically normal child trisomic for the same 13q14 segment. Both sibs displayed the expected proportionate gene dosage effects for ESD. A 153% value of ESD activity was found in the amniotic cells indicating unambiguously that the fetus was not monosomic for segment 13q14 and therefore not at increased risk for Rb. The mother delivered a phenotypically normal child who was confirmed to be trisomic for segment 13q14 by cytogenetic analysis and by gene dosage studies for ESD in cord blood cells and in lymphoblastoid cells.
Assuntos
Carboxilesterase , Hidrolases de Éster Carboxílico/genética , Deleção Cromossômica , Cromossomos Humanos 13-15 , Neoplasias Oculares/diagnóstico , Retinoblastoma/diagnóstico , Âmnio/fisiologia , Células Cultivadas , Neoplasias Oculares/genética , Feminino , Fibroblastos/fisiologia , Humanos , Cariotipagem , Linfócitos/fisiologia , Masculino , Gravidez , Retinoblastoma/genética , Pele/fisiopatologiaRESUMO
We report our experience of 15 cases of gastroschisis which occurred between 1981 and 1993. All but one were diagnosed antenatally by ultrasound between 16 and 32 weeks of pregnancy. We made a termination of the pregnancy in 3 cases, for multiple malformations in 2 cases and one case of very early premature rupture of the membranes (PROM). When checked (11 cases), the karyotype was normal. We made a cesarean section in 11 cases: the indication was a complication for 6 (fetal distress, PROM, polyhydramnios, large dilatation of the gut). We noted growth retardation in 7 newborns and prematurity in 5/12 (mean gestational age of 36.8 weeks). The preoperative study of the gut noted 5 cases with intestinal damage and one case of complete necrosis of the gut. The global prognosis is not as good as usual, with a perinatal mortality of 41.6% (5/12). We discuss this latter point and examine the literature.
Assuntos
Músculos Abdominais/anormalidades , Doenças Fetais/diagnóstico , Diagnóstico Pré-Natal , Músculos Abdominais/cirurgia , Amniocentese , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/genética , Feminino , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/genética , Humanos , Recém-Nascido , Cariotipagem , Gravidez , Resultado da Gravidez , Prognóstico , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
The authors report a family with triphalangeal thumb with nail hypoplasia: one of them has also split feet. They believe that the existence of such families must make very circumspect with regard to genetic counseling for a minor problem such as triphalangeal thumb.
Assuntos
Dedos/anormalidades , Deformidades Congênitas do Pé/genética , Aconselhamento Genético , Deformidades Congênitas da Mão/genética , Aberrações Cromossômicas/genética , Aberrações Cromossômicas/prevenção & controle , Transtornos Cromossômicos , Feminino , Deformidades Congênitas do Pé/prevenção & controle , Genes Dominantes/genética , Deformidades Congênitas da Mão/prevenção & controle , Humanos , Masculino , Linhagem , Fatores de RiscoRESUMO
The authors report Larsen Syndrome in a male newborn with severe cervical spine malformations: segmentation abnormalities of the cervical spine and atlanto-axial dislocation. The severity of the cervical malformations occurring more often in the autosomal recessive form is emphasized.
Assuntos
Anormalidades Múltiplas/genética , Vértebras Cervicais/anormalidades , Aberrações Cromossômicas/genética , Ossos Faciais/anormalidades , Anormalidades Múltiplas/diagnóstico , Articulação Atlantoccipital/anormalidades , Articulação Atlantoccipital/patologia , Vértebras Cervicais/patologia , Transtornos Cromossômicos , Ossos Faciais/patologia , Luxação Congênita de Quadril/diagnóstico , Luxação Congênita de Quadril/genética , Humanos , Lactente , Recém-Nascido , Luxações Articulares/genética , Imageamento por Ressonância Magnética , Masculino , SíndromeRESUMO
Brittany is celtic, like Ireland and Wales where the incidence of neural tube defects is raised. We searched the hospital files in Brittany for all live and still births, and terminations of pregnancy after prenatal diagnosis for the years 1975-1984. 225 cases of spina bifida and 210 cases of anencephaly were identified; giving an incidence of 0.60 per 1000 births for spina bifida and 0.56 per 1000 births for anencephaly. No seasonality was found for both malformations. Analysis of the sex ratio for anencephaly indicated significantly higher proportion of females to males. Maternal age in the affected group was similar to the normal population. Casual heterogeneity among neural tube defects patients was presumed because 14% of our cases had other congenital anomalies.
Assuntos
Anencefalia/epidemiologia , Espinha Bífida Oculta/epidemiologia , Anormalidades Múltiplas/epidemiologia , Anencefalia/mortalidade , Feminino , França , Humanos , Recém-Nascido , Masculino , Idade Materna , Estudos Retrospectivos , Estações do Ano , Fatores Sexuais , Espinha Bífida Oculta/mortalidadeRESUMO
BACKGROUND: The effects of volume expansion on the cardiac output (CO) of newborns have not been studied, so that the indications for colloid infusion are not well standardized. POPULATION AND METHODS: Twenty one newborns (14 preterm and seven term babies) were studied before the 7th day of life. Thirteen had patent ductus arteriosus (PDA) and six had ischemic cardiopathy. Hemodynamic data indicated that these babies should be given 20 ml/kg of a 10% albumin solution. Pulsed-wave Doppler echocardiography was performed before and after infusion. RESULTS: Only 11 newborns had initial low Co (less than 260 ml/kg/min in patients with PDA; less than 200 ml/kg/min in the others). The increases in CO (31 +/- 25% vs 7 +/- 11%, P < 0.01) and of mean aortic flow velocity (MAFV) (34.6 +/- 19.5% vs 7.2 +/- 6.1%, P < 0.01) were significantly greater in this group. The increases in mean arterial pressure (+4 +/- 5 mmHg) and CO (+20 +/- 18%) were significant (P < 0.01) for all patients, both premature and term (with or without PDA and ischemic cardiopathy). The increase in CO was correlated with the initial CO and the cutaneous refilling time but was not correlated with the increase in arterial pressure. The sizes of the ventricles and left atrium grew significantly but that of the right atrium did not. Analysis of the increase in stroke volume in terms of the end diastolic diameter of the left ventricle indicated that the cardiac reserves varied according to the Starling relation. CONCLUSION: Evaluation of MAFV and CO plus diagnosis of PDA are all needed in order to assess whether volume expansion is accurate or not, since, clinical data obtained during the neonatal period are insufficient to do this.
Assuntos
Albuminas/administração & dosagem , Débito Cardíaco , Ecocardiografia Doppler , Volume Cardíaco , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/fisiopatologia , Humanos , Recém-Nascido , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologiaRESUMO
We have studied neural tube malformations in twins in order to research into the role of genetic and environmental factors. 12 pairs of twins in which one child had a neural tube defect were studied in Brittany, which is a Celtic country. We found no evidential agreement about the role each factor played. On the other hand there was an excess of twins in the siblings of those with neural tube defects, especially in the siblings of the mothers. There were more dizygotic twin mothers. Analysing the literature has made it possible for us to find a level of agreement of 7.5% for monozygotic twins and 4.6% for dizygotic twins. This last figure corresponds to the recurrence rate found after one case. The aetiological theories are reviewed. Among factors bringing about neural tube defects would seem to be the microenvironment of the uterus and the delay between ovulation and fertilization and implantation of the fertilized egg. Nutrition of the embryo and possible vitamin deficiencies could explain this inter-action between the mother and the fetus. If there is a genetic factor, it is more likely to be maternal than fetal.
Assuntos
Doenças em Gêmeos , Defeitos do Tubo Neural/genética , Anencefalia/genética , Etnicidade , Feminino , França , Humanos , Masculino , Defeitos do Tubo Neural/etiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Espinha Bífida Oculta/genética , Gêmeos Dizigóticos , Gêmeos MonozigóticosRESUMO
We have recently studied a large family of 80 persons in which 47 were examined. The evaluation included history, blood pressure determination, palpation of the thyroid gland and determination of serum carcino-embryonic antigen (C.E.A.) and calcitonin (C.T.). Two members of the kindred had a proven M.C.T. without pheochromocytoma, hyperparathyroidism or Cushing's disease and two others a probable M.C.T. Four members suffered from intestinal occlusion and death occurred in three of them. Our conclusions are: 1) In this family traced through 4 generations: it appears that M.C.T. is transmitted as an autosomal dominant trait with a high degree of penetrance; 2) Our cases associated with those reported in the literature in the past few years point to the existence of a rare but distinct syndrome characterised by the association of M.C.T. and congenital megacolon with hyperplasia of the myenteric plexus; 3) As far as we know, this is the first indication of C.E.A. coupled with elevated calcitonin among several individuals of the same family. We confirm here the conclusions of previous studies: "C.E.A. is a valuable tumour marker which can be used for the detection of M.C.T., particularly if no calcitonin radio-immuno assay is available.
Assuntos
Carcinoma/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Calcitonina/sangue , Antígeno Carcinoembrionário/análise , Carcinoma/diagnóstico , Criança , Feminino , Genes Dominantes , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Linhagem , Risco , Neoplasias da Glândula Tireoide/diagnósticoRESUMO
We have recently studied a kindred in which there have been 2 proven and 2 probable cases of medullary thyroid carcinoma without pheochromocytoma, hyperparathyroidism or Cushing's disease. Four other members suffered from intestinal occlusion and death occurred in three of them. The family has been traced through 4 generations (80 members) and 47 members could be examined; circulating calcitonin and carcinoembryonic antigen levels were measured. This study leads to two conclusions: 1) Medullary thyroid carcinoma is transmitted as an autosomal dominant trait with a high degree of penetrance. 2) Carcinoembryonic antigen is a valuable tumour marker particularly if no calcitonin radioimmunoassay is avialable for the diagnosis of M.C.T.
Assuntos
Carcinoma/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Calcitonina/sangue , Antígeno Carcinoembrionário/análise , Carcinoma/sangue , Feminino , Humanos , Linhagem , Neoplasias da Glândula Tireoide/sangueRESUMO
17 chromosome abnormalities were found out of 571 small-for-dates newborn babies. 7 of these were trisomy 18, 5 trisomy 21, and 2 trisomy 13. The obstetric and paediatric implications of the fact that 3 percent of small-for-dates babies are carriers of a chromosome abnormality are discussed.
Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos , Retardo do Crescimento Fetal/genética , Recém-Nascido Pequeno para a Idade Gestacional , Cromossomos Humanos 13-15 , Cromossomos Humanos 16-18 , Síndrome de Down/complicações , Feminino , Retardo do Crescimento Fetal/complicações , Humanos , Recém-Nascido , Gravidez , Trissomia , Síndrome de Turner/complicaçõesRESUMO
A prospective comparative study of 300 placentas of premature births and 300 full-term placentas demonstrated that in the former there was a higher frequency of certain types of anomalies: abnormal placental insertion; premature involution of the base plate; signs of fetal hypoxia; placental inflammation. In practice, however, pathological examination of the placenta appears to be of interest only for detecting inflammatory lesions.
Assuntos
Parto Obstétrico , Trabalho de Parto Prematuro/patologia , Placenta/patologia , Feminino , Hipóxia Fetal/patologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Inflamação/patologia , Placenta/irrigação sanguínea , Doenças Placentárias/patologia , Gravidez , Cordão Umbilical/patologiaRESUMO
We have seen two cases of diprosopy associated with anencephaly in Brittany between 1975 and 1984. Diprosopy is a partial or total duplication of the face. It consists of the phenomenon of late division in the embryo of the cephalic portion of the neural plate between the 16th and the 18th days. This gives rise to an incomplete type of monozygotic twinning or a conjoint twin. There are several different forms of the organs that are duplicated. We have seen a case of diprosopos distomos dirhinos diophthalmos and a case of disprosopos distomos dirhinos triophthalmos. These two cases were associated with anencephaly, the second also having a spina bifida and a diaphragmatic hernia. One can explain the incidence of anencephalies in cases of diprosopies by the desturbance created by the latter on the embryological events that succeed it. The delay in nerve formation makes it impossible for the neural tube to close completely, and this is why sometimes the anencephaly is associated with spina bifida. In more general terms one can postulate that all conjoint twins that are, of course, monozygotic and monochorial can interfere with early enbryological development and increase the risks of failure of the neural tube to close.