Vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases are the hallmarks of the genetic disorder spondyloenchondrodysplasia. We mapped a locus in five consanguineous families to chromosome 19p13 and identified mutations in ACP5, which encodes tartrate-resistant phosphatase (TRAP), in 14 affected individuals and showed that these mutations abolish enzyme function in the serum and cells of affected individuals. Phosphorylated osteopontin, a protein involved in bone reabsorption and in immune regulation, accumulates in serum, urine and cells cultured from TRAP-deficient individuals. Case-derived dendritic cells exhibit an altered cytokine profile and are more potent than matched control cells in stimulating allogeneic T cell proliferation in mixed lymphocyte reactions. These findings shed new light on the role of osteopontin and its regulation by TRAP in the pathogenesis of common autoimmune disorders.

The 22q11.2 deletion syndrome (22q11DS) is one of the most recognizable causes of congenital heart defects (CHDs), but the frequency varies in non-selected populations. The purpose of this study was to determine the incidence and clinical features of patients with CHD and 22q11DS admitted to a pediatric cardiology intensive care unit in Brazil. In a prospective study, we evaluated a consecutive series of 207 patients with a CHD following a clinical protocol and cytogenetic analysis by high resolution karyotype and fluorescent in situ hybridization (FISH). 22q11DS was identified in four patients (2%), a frequency similar to studies that evaluated subjects with major CHDs in other countries. Despite this similarity, we believe that the low rate of prenatal identification of CHDs and the limited access of these patients to appropriate diagnosis and care, which occur in our region, could have had an influence on this frequency. It is possible that 22q11DS patients with a severe CHD could have died before having a chance to access a tertiary hospital, leading to an underestimate of its frequency.

Oculo-auriculo-vertebral spectrum (OAVS) is a rare condition characterized by the involvement of the first branchial arches. Purpose To investigate the ear abnormalities of a sample of patients with OAVS. Materials and methods The sample consisted of 12 patients with OAVS seen at the Clinical Genetics Unit, UFCSPA/CHSCPA. The study included only patients who underwent mastoid computed tomography and with normal karyotype. We performed a review of its clinical features, giving emphasis to the ear findings. Results Nine patients were male, the ages ranged from 1 day to 17 years. Ear abnormalities were observed in all patients and involved the external (n=12), middle (n=10) and inner ear (n=3). Microtia was the most frequent finding (n=12). The most common abnormalities of the middle ear were: opacification (n=2), displacement (n=2) and malformation of the ossicular chain. Agenesis of the internal auditory canal (n=2) was the most frequent alteration of the inner ear. Conclusions Ear abnormalities are variable in patients with OAVS and often there is no correlation between findings in the external, middle and inner ear. The evaluation of these structures is important in the management of individuals with OAVS.

CONTEXT AND OBJECTIVE: Oculo-auriculo-vertebral spectrum (OAVS) is considered to be a defect of embryogenesis involving structures originating from the first branchial arches. Our objective was to describe the clinical and cytogenetic findings from a sample of patients with the phenotype of OAVS. DESIGN AND SETTING: Cross-sectional study in a referral hospital in southern Brazil. METHODS:The sample consisted of 23 patients who presented clinical findings in at least two of these four areas: orocraniofacial, ocular, auricular and vertebral. The patients underwent a clinical protocol and cytogenetic evaluation through high-resolution karyotyping, fluorescence in situ hybridization for 5p and 22q11 microdeletions and investigation of chromosomal instability for Fanconi anemia. RESULTS: Cytogenetic abnormalities were observed in three cases (13%) and consisted of: 47,XX,+mar; mos 47,XX,+mar/46,XX; and 46,XX,t(6;10)(q13; q24). We observed cases of OAVS with histories of gestational exposition to fluoxetine, retinoic acid and crack. One of our patients was a discordant monozygotic twin who had shown asymmetrical growth restriction during pregnancy. Our patients with OAVS were characterized by a broad clinical spectrum and some presented atypical findings such as lower-limb reduction defect and a tumor in the right arm, suggestive of hemangioma/lymphangioma. CONCLUSIONS: We found a wide range of clinical characteristics among the patients with OAVS. Different chromosomal abnormalities and gestational expositions were also observed. Thus, our findings highlight the heterogeneity of the etiology of OAVS and the importance of these factors in the clinical and cytogenetic evaluation of these patients.RESUMO CONTEXTO E OBJETIVO: O espectro oculoauriculovertebral (EOAV) é considerado um defeito de embriogênese envolvendo estruturas originadas a partir dos primeiros arcos branquiais. Nosso objetivo foi descrever os achados clínicos e citogenéticos de uma amostra de pacientes com fenótipo de EOAV. TIPO DE ESTUDO E LOCAL: Estudo transversal em um hospital de referência no sul do Brasil. MÉTODOS: A amostra foi composta de 23 pacientes que apresentaram achados clínicos em pelo menos duas das quatro áreas: orocraniofacial, oculares, auriculares e vertebrais. Os pacientes foram submetidos a um protocolo clínico e avaliação citogenética através do cariótipo de alta resolução, hibridização in situ fluorescente para as microdeleções 5p e 22q11 e pesquisa de instabilidade cromossômica para anemia de Fanconi. RESULTADOS: Alterações citogenéticas foram observadas em três casos (13%) e consistiam de: 47,XX,+mar; mos 47,XX,+mar/46,XX e 46,XX,t(6;10)(q13;q24). Observamos casos de EOAV com história de exposição gestacional à fluoxetina, ácido retinoico e crack. Um dos nossos pacientes foi um gêmeo monozigótico discordante que teve restrição de crescimento assimétrica durante a gravidez. Nossos pacientes com EOAV foram caracterizados por um amplo espectro clínico e alguns apresentaram achados clínicos atípicos como um defeito de reduç...

Trisomy 18 is a chromosomal syndrome characterized by a broad clinical picture, as well as a very reserved prognosis. The aim of our study was to verify the clinical characteristics and survival of patients diagnosed in a referral hospital in southern Brazil. Our sample consisted of 31 patients, 22 were female (71%), ages ranging from 1 to 1,395 days (median 14 days). The majority had a single cell lineage with full trisomy of chromosome 18 (94%). Concerning pregnancy complications, pre-eclampsia was the main abnormality described (17%). Fetal ultrasound was performed in 23 cases, and the most frequent abnormalities were polyhydramnios (41%) and intrauterine growth retardation (27%). There were no reports of prenatal identification of the syndrome. Most patients were born by cesarean due to pregnancy and fetal complications and about half of the cases were premature. Congenital heart defects represented the main major malformation observed (94%). Thirty patients (97%) progressed to death (survival ranged from 2 to 780 days, and 87% died within the first 6 months of life). Trisomy 18 is a serious chromosomal disorder with limited survival. Abnormalities of pregnancy appear to be frequent, which can lead to complications for both fetus and mother. The prenatal identification of these patients in our country is still inadequate, resulting in important implications for genetic counseling and management of these patients and their families. And this makes the possibility of interruption of pregnancy, regardless of ethical factors involved, an unlikely option.

The malformations associated with in utero exposure to these chemotherapeutic agents are highly variable, but growth deficiency and anomalies of the craniofacial region and limbs are the most common. The pattern of malformations in children who were congenitally exposed to chemotherapeutic agents appears to be directly related to the age at and duration of exposure, rather than to the specific drug itself. Effective contraception is essential for the safe use of a potential teratogen in nonpregnant women of reproductive age.

Objective: To describe the central nervous system (CNS) alterations present in a sample of oculo-auriculo-vertebral spectrum (OAVS) patients, trying to correlate them with other clinical features. Method: Seventeen patients with diagnosis of OAVS were evaluated. All presented radiological evaluation of the CNS, normal GTG-Banding karyotype and clinical features involving at least two from the four following areas: oro-cranio-facial, ocular, auricular and vertebral. results: CNS alterations were verified in eight from seventeen patients (47%). Diffuse cerebral hypoplasia, dilated lateral cerebral ventricles (asymptomatic hydrocephalus), corpus callosum dysgenesis and frontal hypodensities were the most frequent abnormalities. Presence of ophthalmologic abnormalities was the only clinical association observed, being significantly more frequent among patients with cerebral alterations (63% versus 11%). conclusion: CNS abnormalities are frequent in patients with OAVS, especially in carriers of ophthalmologic alterations. However, the absence of detectable cerebral abnormalities did not exclude the possibility that these subjects will subsequently present neurological symptoms. Key words: Goldenhar syndrome, facial asymmetry, central nervous system, eye abnormalities.Anormalidades do sistema nervoso central em pacientes com espectro óculo-aurículo-vertebral (síndrome de Goldenhar) resuMO Objetivo: Descrever as alterações do sistema nervoso central (SNC) presentes em uma amostra de pacientes com espectro óculo-aurículo-vertebral (EOAV), tentando correlacioná-las com os demais achados clínicos. Método: Foram avaliados dezessete pacientes com diagnóstico de EOAV. Todos apresentavam avaliação radiológica do SNC, cariótipo por bandas GTG normal e achados clínicos em pelo menos duas das quatro das seguintes áreas: oro-crânio-facial, ocular, auricular e vertebral. resultados: Alterações do SNC foram verificadas em oito dos dezessete pacientes (47%). Hipoplasia cerebral difusa, dilatação dos ventrículos cerebrais laterais (hidrocefalia assintomática), disgenesia do corpo caloso e hipondesidades frontais foram as anormalidades mais frequentes. A presença de anormalidades oftalmológicas foi a única associação clínica observada, sendo significativamente mais comum entre pacientes com alterações cerebrais (63% versus 11%). conclusão: Anormalidades do SNC são frequentes entre pacientes com EOAV, especialmente em portadores de alterações oftalmológicas. Entretanto, a ausência de anormalidades cerebrais detectáveis não exclui a possibilidade de que estes indivíduos venham subseqüentemente a apresentar sintomas neurológicos. Palavras-chave: síndrome de Goldenhar, assimetria facial, sistema nervoso central, anormalidades do olho.

Knowledge on the clinical picture and on the prognosis of Edwards syndrome patients is of great importance regarding the neonatal care and the decisions about invasive treatments. The speed to have a confirmed diagnosis is important for making decisions about medical procedures. Often, interventions are performed under emergency conditions, without many opportunities for discussion, and they involve difficult medical and ethical issues.