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Bosma arhinia microphthalmia syndrome (BAMS, OMIM #603457) is a rare autosomal dominant disorder caused by heterozygous variation in the SMCHD1 gene on chromosome 18p11. Clinically, it is characterized by microphthalmia, absence or hypoplasia of nose, choanal atresia, anosmia, palatal abnormalities, hypogonadotropic hypogonadism, and cryptorchidism. Here we report a Brazilian patient with a likely pathogenic variation in SMCHD1 gene (c.1418A>T; p.Glu473Val) presenting hemiarhinia associated with short stature and hypogonadotropic hypogonadism. Due to the clinical variability of BAMS, we considered that hemiarhinia, without microphthalmia, in the present case, can be considered a mild form of BAMS and could be considered for screening of SMCHD1 gene variation.
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OBJECTIVE: This study analyzed the systemic and oral abnormalities in individuals with Kabuki syndrome (KS) that might be investigated to enhance the early diagnosis and treatment by a multidisciplinary team, minimizing the consequences to the individual's health. STUDY DESIGN: Clinical examination was conducted on 15 individuals to investigate orodental alterations such as tooth abnormalities and cleft lip and/or palate, and the patient records were also reviewed to investigate systemic diseases such as cardiopathies, infectious and immunologic diseases, nephropathies, and delayed neuropsychomotor development. RESULTS: All individuals with KS presented cleft lip and/or palate, 11 (73.34%) tooth abnormalities, 5 (33.34%) congenital cardiopathies, 12 (80%) infectious or immunologic diseases, 1 (6.67%) nephropathy, and 14 (93.34%) had an intellectual disability. CONCLUSION: Individuals with KS often have dental anomalies such as hypodontia, cleft or palate, and systemic disorders such as congenital heart disease and infectious diseases. Intellectual disability is present in most cases. These alterations should be investigated as early as possible to prevent the increase in morbidity in these individuals.
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Anormalidades Múltiplas , Face/anormalidades , Doenças Vestibulares , Humanos , Feminino , Masculino , Doenças Vestibulares/complicações , Criança , Pré-Escolar , Adolescente , Anormalidades Dentárias , Adulto , Deficiência Intelectual/complicações , Lactente , Fissura Palatina/complicações , Doenças Hematológicas/complicaçõesRESUMO
CHARGE syndrome is a rare autosomal dominant syndrome characterized by multiple congenital anomalies including coloboma, heart defects, ear anomalies, and developmental delay, caused by pathogenic variants in the CHD7 gene. The discovery of the molecular basis of this syndrome increased the number of cases reported and expanded the phenotype and clinical variability. Limb anomalies are occasional clinical findings in this syndrome, present in about 30% of reported cases. The occurrence of limb anomalies in this syndrome suggests that it should be considered as part of the phenotypic spectrum. Here, we describe an individual with CHARGE syndrome presenting unilateral monodactyly.
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Síndrome CHARGE , DNA Helicases , Fenótipo , Humanos , Síndrome CHARGE/genética , Síndrome CHARGE/diagnóstico , Síndrome CHARGE/patologia , Síndrome CHARGE/complicações , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Masculino , Feminino , Mutação , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/patologia , Deformidades Congênitas dos Membros/diagnósticoRESUMO
The oculoauriculofrontonasal syndrome (OAFNS) is a rare condition, with unknown etiology, characterized by the association of frontonasal dysplasia (FND) and oculoauriculovertebral spectrum (OAVS). Main clinical findings include widely spaced eyes, epibulbar dermoid, broad nose, mandibular hypoplasia, and preauricular tags. Here, we describe a case series of 32 Brazilian individuals with OAFNS and review the literature ascertaining individuals presenting phenotypes compatible with the diagnosis of OAFNS, aiming to refine the phenotype. This series emphasizes the phenotypic variability of the OAFNS and highlights the occurrence of rare craniofacial clefts as a part of the phenotype. The ectopic nasal bone, a hallmark of OAFNS, was frequent in our series, reinforcing the clinical diagnosis. The absence of recurrence, consanguinity, chromosomal, and genetic abnormalities reinforces the hypothesis of a nontraditional inheritance model. The phenotypic refinement provided by this series contributes to an investigation regarding the etiology of OAFNS.
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Anormalidades do Olho , Síndrome de Goldenhar , Humanos , Orelha Externa/anormalidades , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/genética , Coluna Vertebral/anormalidades , Síndrome de Goldenhar/diagnóstico , FenótipoRESUMO
INTRODUCTION: Craniofacial clefts are rare congenital anomalies that might involve both soft tissue and skeletal components. The association of Tessier cleft number 3 and 4 with choanal atresia appears to be unusual and only few clinical cases have been reported in published literature. OBJECTIVES: Report a series of 13 cases of choanal atresia in patients with Tessier numbers 3 or 4 clefts and the literature review on this topic. METHODS: A literature review was undertaken via PUBMED database before April 2020 addressing the association between Tessier numbers 3 or 4 clefts and choanal atresia. Retrospective chart review of patients diagnosed with both comorbidities at a tertiary hospital expertised in craniofacial anomalies. RESULTS: Literature review yielded 10 studies describing the relationship between choanal atresia and Tessier 3 and 4 facial clefts. We identified 98 patients diagnosed with medial oro-ocular facial clefts (Tessier 3 and 4) and 119 with choanal atresia at our institution over a 20 years time period. Altogether, 13 individuals were diagnosed with both malformations, 3 patients with number 3 cleft, and 10 patients with number 4 cleft. It represents 13.26% of the cases. CONCLUSION: This study highlights the features of Tessier 3 and 4 facial clefts associated with choanal atresia. Although the publications regarding this association are very scarce, the authors present the largest series of cases of Tessier number 3 and 4 clefts with choanal atresia showing that association between these conditions could be not so unusual.
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Atresia das Cóanas , Anormalidades Craniofaciais , Face/anormalidades , Humanos , Estudos RetrospectivosRESUMO
The authors describe the clinical findings observed in a Brazilian girl that are suggestive of microphthalmia and linear skin defects (MLS) also known as MIDAS syndrome (OMIM #309801). She also presented with short stature, agenesis of corpus callosum, cleft palate, enamel defects, and genitourinary anomalies, which are rarely reported within the clinical spectrum of MLS. The 11,5 Mb deletion in Xp22.3p22.2 observed in the patient includes the entire HCCS gene (responsible for the MLS phenotype) and also encompasses several other genes involved with behavioral phenotypes, craniofacial and central nervous system development such as MID1, NLGN4X, AMELX , ARHGAP6, and TBL1X. The whole clinical features of our proband possibly represents an unusual MLS syndromic phenotype caused by an Xp22.3p22.2 continuous gene deletion.
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In this article, we report on a Brazilian female patient born to consanguineous parents and presenting with alobar holoprosencephaly, severe eye involvement, and unusual skin hyperpigmented lesions. She was found to have a mutation (c.2240T > C; p.Val751Gly) in exon 15 of the PTCH1 gene. Mutations in this gene are associated with the nevoid basal cell carcinoma syndrome (NBCCS, OMIM 109400) and, in other instances, with holoprosencephaly (holoprosencephaly-7, OMIM 610828). Severe eye involvement ranging from orbital coloboma to microphthalmia has been seldom reported in patients with NBCCS with PTCH1 mutations. To our knowledge, this is the first report of an individual with central nervous system, skin, and eye manifestations due to a PTCH1 mutation. Mechanisms involved in these multisystem manifestations are discussed.
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Auriculocondylar syndrome is a rare craniofacial disorder comprising core features of micrognathia, condyle dysplasia and question mark ear. Causative variants have been identified in PLCB4, GNAI3 and EDN1, which are predicted to function within the EDN1-EDNRA pathway during early pharyngeal arch patterning. To date, two GNAI3 variants in three families have been reported. Here we report three novel GNAI3 variants, one segregating with affected members in a family previously linked to 1p21.1-q23.3 and two de novo variants in simplex cases. Two variants occur in known functional motifs, the G1 and G4 boxes, and the third variant is one amino acid outside of the G1 box. Structural modeling shows that all five altered GNAI3 residues identified to date cluster in a region involved in GDP/GTP binding. We hypothesize that all GNAI3 variants lead to dominant negative effects.
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Otopatias/genética , Orelha/anormalidades , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Variação Genética , Região Branquial/metabolismo , Brasil , Otopatias/diagnóstico , Feminino , Humanos , Masculino , Linhagem , Fenótipo , Conformação ProteicaRESUMO
Most patients with Kabuki syndrome (KS) are the only person in their family with the condition. However, familial cases of KS have been described showing evidence that this syndrome can be inherited as a dominant trait with variable expressivity. We report on two related individuals with facial findings characteristic of KS. The proposita had arched eyebrows, long and upward slanting palpebral fissures, cleft lip and palate, retromicrognathia, brachydactyly of hands and feet, stubby fingers, nail hypoplasia, and prominent finger pads. Her mother had eyebrows with dispersed lateral half, long and upward slanting palpebral fissures, retrognathia, abnormal and posteriorly rotated ears, prominent finger pads, brachydactyly of feet, learning difficulties, and psychomotor development delay. DNA sequencing revealed a novel missense mutation in the MLL2 gene in both the proposita and her mother. The mutation (p.R5432Q) was found in the exon 51, within the SET domain of the gene, which confers methyltransferase activity on the protein. Therefore, the epigenetic and transcriptional regulatory properties of this protein may be altered and this suggests that the mutation is the cause of phenotype observed in both the patient and her mother. The clinical signs and the molecular evidence in this family further support the notion that KS is an autosomal dominant condition with variable expressivity. To our knowledge this is the first report of a Brazilian family with recurrence of this syndrome.
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Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Doenças Hematológicas/genética , Proteínas de Neoplasias/genética , Doenças Vestibulares/genética , Brasil , Face/anormalidades , Feminino , Humanos , Lactente , Masculino , LinhagemRESUMO
The authors describe on a Brazilian girl with coronal synostosis, facial asymmetry, ptosis, brachydactyly, significant learning difficulties, recurrent scalp infections with marked hair loss, and elevated serum immunoglobulin E. Standard lymphocyte karyotype showed a small additional segment in 7p21[46,XX,add(7)(p21)]. Deletion of the TWIST1 gene, detected by Multiplex Ligation Probe-dependent Amplification (MPLA) and array-CGH, was consistent with phenotype of Saethre-Chotzen syndrome. Array CGH also showed deletion of four other genes at 7p21.1 (SNX13, PRPS1L1, HD9C9, and FERD3L) and the deletion of six genes (CACNA2D2, C3orf18, HEMK1, CISH, MAPKAPK3, and DOCK3) at 3p21.31. Our case reinforces FERD3L as candidate gene for intellectual disability and suggested that genes located in 3p21.3 can be related to hyper IgE phenotype.
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Acrocefalossindactilia/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 3 , Cromossomos Humanos Par 7 , Síndrome de Job/genética , Deficiências da Aprendizagem/genética , Acrocefalossindactilia/complicações , Acrocefalossindactilia/diagnóstico , Criança , Pré-Escolar , Bandeamento Cromossômico , Deleção Cromossômica , Hibridização Genômica Comparativa , Fácies , Feminino , Humanos , Lactente , Síndrome de Job/complicações , Síndrome de Job/diagnóstico , Deficiências da Aprendizagem/complicações , Deficiências da Aprendizagem/diagnóstico , FenótipoRESUMO
Auriculo-condylar syndrome (ACS) is characterized by typical ears malformation (so-called "question mark" ears), prominent cheeks, microstomia, and abnormality of the temporomandibular joint and condyle of the mandible. In this report we describe a new simplex case and a previously unreported family with affected individuals in three generations documenting clinical variability. Linkage study for markers located in candidate region for ACS1 (1p21.1-q23.3) was excluded in our familial case, reinforcing the hypothesis of genetic heterogeneity for this condition. A review of the literature focusing diagnostic criteria and features of ACS was performed.
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Otopatias/diagnóstico , Otopatias/genética , Brasil , Criança , Cromossomos Humanos Par 1/genética , Orelha/anormalidades , Feminino , Heterogeneidade Genética , Ligação Genética , Humanos , Mandíbula/anormalidades , Microstomia/genética , Linhagem , Articulação Temporomandibular/anormalidadesRESUMO
Oculoauriculovertebral spectrum (OAVS; OMIM 164210) is a complex condition characterized by defects of aural, oral, mandibular and vertebral development. The aetiology of this condition is likely to be heterogeneous; most cases are sporadic, however, familial cases suggesting autosomal recessive and autosomal dominant inheritance have been reported. In this study, we describe the clinical aspects of nine familial cases with evidence of autosomal dominant inheritance and compare them with reports in the literature. Interfamilial and intrafamilial clinical variabilities were observed in this study (reinforcing the necessity of careful examination of familial members). We suggest that oculoauriculovertebral spectrum with autosomal dominant inheritance is characterized mainly by bilateral auricular involvement and rarely presents extracranial anomalies.
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Anormalidades Múltiplas/genética , Genes Dominantes , Síndrome de Goldenhar/genética , Anormalidades Múltiplas/diagnóstico , Adolescente , Criança , Pré-Escolar , Família , Feminino , Síndrome de Goldenhar/diagnóstico , Humanos , Lactente , MasculinoAssuntos
Anormalidades Múltiplas/patologia , Anoftalmia/patologia , Nariz/anormalidades , Fenótipo , Crânio/anormalidades , Anoftalmia/diagnóstico por imagem , Encéfalo/anormalidades , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/patologia , Humanos , Lactente , Deficiência Intelectual/patologia , Masculino , Nariz/patologia , Índice de Gravidade de Doença , Crânio/diagnóstico por imagem , Síndrome , UltrassonografiaRESUMO
OBJECTIVE: To report on two Brazilian patients with chromosome 22q11 deletion who presented with velopharyngeal insufficiency, congenital heart anomalies, developmental delay, and limb anomalies. The pattern of limb anomalies in these patients, which range from ectrodactyly to limb synostosis, is very uncommon in 22q11 deletion syndrome. CONCLUSION: These patients widen the spectrum of clinical signs of the 22q11 deletion syndrome and alert researchers to conduct additional investigation in patients with limb involvement with velopharyngeal insufficiency and/or cardiac anomalies, along with developmental delay.
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Síndrome de DiGeorge/diagnóstico , Criança , Deficiências do Desenvolvimento/genética , Síndrome de DiGeorge/genética , Dedos/anormalidades , Seguimentos , Cardiopatias Congênitas/genética , Humanos , Masculino , Sindactilia/genética , Dedos do Pé/anormalidades , Insuficiência Velofaríngea/genéticaAssuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Ossos do Pé/anormalidades , Ossos da Mão/anormalidades , Transtornos da Pigmentação , Anormalidades Múltiplas/patologia , Doenças do Desenvolvimento Ósseo/patologia , Brasil , Pré-Escolar , Feminino , Fibroma/patologia , Humanos , Recém-Nascido , Transtornos da Pigmentação/patologiaRESUMO
BACKGROUND: Cardio-facial-cutaneous syndrome. AIM: To describe the clinical findings of a patient with cardio-facial-cutaneous syndrome and to characterize her communication. METHOD: To investigate the following areas: genetic, speech-language and hearing, otolaryngological, and psychological. RESULTS: Cardiac, cutaneous, and craniofacial alterations were observed, as well as cognitive deficits and significant language impairment with the absence of oral speech. CONCLUSION: The importance of assessing these patients is highlighted, for diagnostic and intervention purposes, so that the work developed in the speech and language therapy can be better directed.
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Anormalidades Múltiplas/diagnóstico , Transtornos da Articulação/diagnóstico , Anormalidades Craniofaciais/diagnóstico , Cardiopatias Congênitas/diagnóstico , Anormalidades da Pele/diagnóstico , Adulto , Audiometria de Resposta Evocada , Feminino , Humanos , Síndrome de Noonan/diagnóstico , Emissões Otoacústicas Espontâneas , SíndromeRESUMO
Tema: sindrome Cárdio-fácio-cutâneo. Objetivo: descrever os achados clínicos de uma paciente com a síndrome Cárdio-fácio-cutâneo e caracterizar sua comunicação. Método: realizar avaliação genética, fonoaudiológica, otorrinolaringológica, e psicológica. Resultados: foram observadas as alterações cardíacas , cutâneas e craniofaciais, deficiência cognitiva e alteração significativa da linguagem com ausência de oralidade. Conclusão: ressalta-se a importancia da avaliação destes pacientes, para diagnóstico e intervenção, com o intuito de reflexões que direcionem o trabalho terapêutico fonoaudiológico no favorecimento de condutas comunicativas, mediante alterações severas da comunicação.
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Humanos , Feminino , Adulto , Anormalidades Múltiplas/diagnóstico , Transtornos da Articulação/diagnóstico , Anormalidades Craniofaciais/diagnóstico , Cardiopatias Congênitas/diagnóstico , Anormalidades da Pele/diagnóstico , Audiometria de Resposta Evocada , Síndrome de Noonan/diagnóstico , Emissões Otoacústicas Espontâneas , SíndromeRESUMO
Hearing loss constitutes an important category of congenital defects that can be isolated or part of the phenotypic spectrum of several syndromes. A clinical genetic study was performed on a sample of 144 patients with nonsyndromic hearing loss, establishing the sex distribution, type, degree, symmetry, laterality, progression, etiology, and, when possible, inheritance pattern.
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Perda Auditiva Condutiva/genética , Perda Auditiva Condutiva-Neurossensorial Mista/genética , Perda Auditiva Neurossensorial/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Aberrações Cromossômicas , Diagnóstico Diferencial , Progressão da Doença , Feminino , Genes Dominantes , Genes Recessivos , Inquéritos Epidemiológicos , Perda Auditiva Condutiva/diagnóstico , Perda Auditiva Condutiva/etiologia , Perda Auditiva Condutiva-Neurossensorial Mista/diagnóstico , Perda Auditiva Condutiva-Neurossensorial Mista/etiologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , SíndromeRESUMO
This report describes several relatives in three generations of one family and another, unrelated boy with auriculo-condylar syndrome, a rare autosomal dominant disorder. Variation in the severity of the abnormalities was observed. We discuss the findings in our patients in relation to those in the literature.