RESUMO
Although ubiquitously present, the relevance of cilia for vertebrate development and health has long been underrated. However, the aberration or dysfunction of ciliary structures or components results in a large heterogeneous group of disorders in mammals, termed ciliopathies. The majority of human ciliopathy cases are caused by malfunction of the ciliary dynein motor activity, powering retrograde intraflagellar transport (enabled by the cytoplasmic dynein-2 complex) or axonemal movement (axonemal dynein complexes). Despite a partially shared evolutionary developmental path and shared ciliary localization, the cytoplasmic dynein-2 and axonemal dynein functions are markedly different: while cytoplasmic dynein-2 complex dysfunction results in an ultra-rare syndromal skeleto-renal phenotype with a high lethality, axonemal dynein dysfunction is associated with a motile cilia dysfunction disorder, primary ciliary dyskinesia (PCD) or Kartagener syndrome, causing recurrent airway infection, degenerative lung disease, laterality defects, and infertility. In this review, we provide an overview of ciliary dynein complex compositions, their functions, clinical disease hallmarks of ciliary dynein disorders, presumed underlying pathomechanisms, and novel developments in the field.
Assuntos
Dineínas do Axonema/metabolismo , Ciliopatias/patologia , Dineínas do Citoplasma/metabolismo , Animais , Dineínas do Axonema/química , Dineínas do Axonema/genética , Cílios/metabolismo , Ciliopatias/genética , Ciliopatias/metabolismo , Dineínas do Citoplasma/química , Dineínas do Citoplasma/genética , Humanos , Síndrome de Kartagener/genética , Síndrome de Kartagener/metabolismo , Síndrome de Kartagener/patologia , Polimorfismo Genético , Síndrome de Costela Curta e Polidactilia/genética , Síndrome de Costela Curta e Polidactilia/metabolismo , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
Short ribpolydactyly syndrome type III (SRPS3) is a lethal perinatal skeletal disorder consisting of polydactyly and multisystem organ abnormalities. To further assess the pathogenicity of two pairs of compound heterozygotes and to search for novel molecular etiology, Xrays and hematoxylin and eosin staining were conducted in three cases: Two retrospective samples and a newly identified patient with SRPS3. In addition, nextgeneration sequencing was used to evaluate a fetus with SRPS3. Typical radiological features of the three cases included a long, narrow thorax with short ribs, shortened long bones, spurs at the metaphysis of the long bones and congenital bowing of the femurs. The present study also observed atypical histopathological changes, together with the absence of proliferation and abundance of retaining cartilage in the primary spongiosum. In addition, two novel compound heterozygous variants were identified in the dynein cytoplasmic 2 heavy chain 1 (DYNC2H1) gene of the fetus: NM_001080463.1, c.6591_6593delTGG (chr11:103055738103055740); NM_001080463.1, c.7883T>C (chr11:103070000). The findings of the present study provided further confirmation of the pathogenicity of two compound heterozygous variants in two retrospective samples and identified novel compound heterozygous variants. These findings may improve our knowledge of the histopathological and radiological changes in patients with SRPS3 and the relative effects of DYNC2H1 variants. The findings of the present study may facilitate the clinical and molecular diagnosis of SRPS3.
Assuntos
Dineínas do Citoplasma/metabolismo , Radiografia/métodos , Síndrome de Costela Curta e Polidactilia/diagnóstico por imagem , Adulto , Dineínas do Citoplasma/genética , Feminino , Feto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linhagem , Estudos Retrospectivos , Síndrome de Costela Curta e Polidactilia/genética , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
BACKGROUND: Skeletal ciliopathies are a group of clinically and genetically heterogeneous disorders with the spectrum of severity spanning from relatively mild to prenatally lethal. The aim of our study was to identify pathogenic mutations in a Chinese family with two siblings presenting a Short-rib polydactyly syndrome (SRPS)-like phenotype. METHOD: Karyotyping and NGS-based CNVseq were performed. Obtaining the negative results in karyotyping and CNVseq, whole-exome sequencing (WES) using genomic DNA (gDNA) extracted from the umbilical cord blood of the first fetus was carried out, followed by bioinformation analysis. The candidate pathogenic variants were confirmed by Sanger sequencing in the family. RESULTS: No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the affected fetus with SRPS-like phenotype. WES analysis identified two novel compound heterozygous variants in DYNC2LI1, c.358G>T (p.Pro120Ser; NM_001193464), and c.928A>T (p.Lys310Ter; NM_ 001193464). Bioinformatics analysis suggested that c.358G>T (p.Pro120Ser) was likely pathogenic and c.928A>T (p.Lys310Ter) was pathogenic. Sanger sequencing of the two variants in family reveal that c.358G>T was from paternal origin and c.928A>T was from maternal origin, and the second affected fetus had the same compound heterozygous variants in DYNC2LI1. Definitive diagnosis of short-rib thoracic dysplasia 15 with polydactyly (SRTD15) was made in the family. CONCLUSION: Our results expand the mutational spectrum of DYNC2LI1 in severe skeletal ciliopathies. WES facilitates the accurate prenatal diagnosis of fetal skeletal ciliopathy, and provides helpful information for genetic counseling.
Assuntos
Ciliopatias/genética , Dineínas do Citoplasma/genética , Feto/anormalidades , Mutação Puntual , Síndrome de Costela Curta e Polidactilia/genética , Adulto , Ciliopatias/diagnóstico por imagem , Ciliopatias/patologia , Feminino , Feto/diagnóstico por imagem , Heterozigoto , Humanos , Masculino , Gravidez , Síndrome de Costela Curta e Polidactilia/diagnóstico por imagem , Síndrome de Costela Curta e Polidactilia/patologia , Ultrassonografia Pré-Natal , Sequenciamento Completo do GenomaRESUMO
We report novel causative mutations in the IFT80 gene identified in four fetuses from two unrelated families with Beemer-Langer syndrome (BLS) or BLS-like phenotypes. We discuss the implication of the IFT80 gene in ciliopathies, and its diagnostic value for BLS among other SRPS.
Assuntos
Proteínas de Transporte/genética , Feto/patologia , Mutação , Síndrome de Costela Curta e Polidactilia/genética , Síndrome de Costela Curta e Polidactilia/patologia , Feminino , Feto/anormalidades , Feto/metabolismo , Humanos , Masculino , Linhagem , Fenótipo , Diagnóstico Pré-NatalRESUMO
The short rib polydactyly syndromes (SRPS) are a group of recessively inherited, perinatal-lethal skeletal disorders primarily characterized by short ribs, shortened long bones, varying types of polydactyly and concomitant visceral abnormalities. Mutations in several genes affecting cilia function cause SRPS, revealing a role for cilia function in skeletal development. To identify additional SRPS genes and discover novel ciliary molecules required for normal skeletogenesis, we performed exome sequencing in a cohort of patients and identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one SRPS family. The p.E80K mutation abolished serine/threonine kinase activity, resulting in altered ICK subcellular and ciliary localization, increased cilia length, aberrant cartilage growth plate structure, defective Hedgehog and altered ERK signalling. These data identify ICK as an SRPS-associated gene and reveal that abnormalities in signalling pathways contribute to defective skeletogenesis.
Assuntos
Anormalidades Múltiplas/genética , Proteínas Hedgehog/genética , Proteínas Serina-Treonina Quinases/genética , Síndrome de Costela Curta e Polidactilia/genética , Esqueleto/crescimento & desenvolvimento , Anormalidades Múltiplas/fisiopatologia , Cílios/genética , Cílios/patologia , Exoma/genética , Feminino , Humanos , Lactente , Sistema de Sinalização das MAP Quinases , Linhagem , Gravidez , Análise de Sequência de DNA , Síndrome de Costela Curta e Polidactilia/patologia , Transdução de Sinais , Esqueleto/anormalidadesRESUMO
Short rib-polydactyly syndrome type III (SRPS3) is a perinatal lethal skeletal disorder with polydactyly and multisystem organ abnormalities. While ultrasound of the fetus can detect skeletal abnormalities characteristic of SRPS3, the syndrome is often difficult to diagnose before birth. As SRPS3 is an autosomal recessive disorder, identification of the gene mutations involved could lead to the development of prenatal genetic testing as an accurate method of diagnosis. In this study, we describe genetic screening approaches to identify potential abnormalities associated with SRPS3. Karyotype analysis, array comparative genomic hybridization (aCGH), and next-generation panel sequencing were each performed on a fetus showing signs of the disorder, as well as on the mother and father. Karyotype and aCGH results revealed no abnormalities. However, next-generation panel sequencing identified novel mutations in the DYNC2H1 gene. The fetus was compound heterozygous for both a missense mutation c.8313A > T and a frameshift mutation c.10711_10714delTTTA in the DYNC2H1 gene, which were inherited from the mother and father, respectively. These variants were further confirmed using Sanger sequencing and have not been previously reported. Our study indicates the utility of using next-generation panel sequencing in screening for novel disease-associated mutations.
Assuntos
Hibridização Genômica Comparativa , Dineínas do Citoplasma/genética , Predisposição Genética para Doença , Síndrome de Costela Curta e Polidactilia/genética , Adulto , Feminino , Feto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cariótipo , Mutação , Linhagem , Síndrome de Costela Curta e Polidactilia/diagnóstico por imagem , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
BACKGROUND: The short-rib polydactyly (SRP) syndromes are rare skeletal dysplasias caused by abnormalities in primary cilia, sometimes associated with visceral malformations. METHODS: The pathogenesis of ductal plate malformation (DPM) varies in different syndromes and has not been investigated in SRP. We have studied liver development in five SRP fetuses and pancreatic development in one SRP fetus, with genetically confirmed mutations in cilia related genes, with and without DPMs, using the immunoperoxidase technique, and compared these to other syndromes with DPM. RESULTS: Acetylated tubulin expression was abnormal in DPM in SRP, Meckel syndrome, and autosomal recessive polycystic kidney disease (ARPKD), confirming ciliary anomalies. SDF-1 was abnormally expressed in SRP and two of three cases of autosomal dominant polycystic kidney disease (ADPKD) but not ARPKD or Meckel. Increased density of quiescent hepatic stellate cells was seen in SRP, Meckel, one of three cases of ARPKD, and two of three cases of ADPKD with aberrant hepatocyte expression of keratin 19 in SRP and ADPKD. Immunophenotypic abnormalities were present even in fetal liver without fully developed DPMs. The SRP case with DPM and pancreatic malformations showed abnormalities in the pancreatic head (influenced by mesenchyme from the septum transversum, similar to liver) but not pancreatic body (influenced by mesenchyme adjacent to the notochord). CONCLUSION: In SRP, there are differentiation defects of hepatocytes, cholangiocytes, and liver mesenchyme and, in rare cases, pancreatic mesenchymal anomalies. The morphological changes were subtle in early gestation but immunophenotypic abnormalities were present. Mesenchymal-epithelial interactions may contribute to the malformations. Birth Defects Research (Part A) 106:549-562, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Feto , Fígado , Pâncreas , Síndrome de Costela Curta e Polidactilia , Feminino , Feto/anormalidades , Feto/embriologia , Humanos , Fígado/anormalidades , Fígado/embriologia , Masculino , Pâncreas/anormalidades , Pâncreas/embriologia , Síndrome de Costela Curta e Polidactilia/embriologia , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
The Majewski syndrome or short rib-polydactyly syndrome (SRPS) type II is a lethal skeletal dysplasia characterized by severe IUGR (intrauterine growth restriction) and dysmorphic face, polydactyly, relatively proportionate head size at birth with later progression to microcephaly. A case of second trimester ultrasound diagnosis of SRPS type II is reported with review of the medical record of previous observed cases. Postmortem examination and radiogram confirmed the clinical diagnosis. Histological examination of the femoral epypheseal chondral plate showed an expanded and irregular hypertrophic zone. Moreover, characteristic cortico-medullary cysts of both kidneys and portal fibrosis were also demonstrated; findings consistent with the broad phenotypic spectrum of this rare skeletal disease.
Assuntos
Lâmina de Crescimento/diagnóstico por imagem , Rim/diagnóstico por imagem , Fígado/diagnóstico por imagem , Síndrome de Costela Curta e Polidactilia/diagnóstico por imagem , Adulto , Feminino , Lâmina de Crescimento/patologia , Humanos , Rim/patologia , Fígado/patologia , Gravidez , Diagnóstico Pré-Natal , Síndrome de Costela Curta e Polidactilia/patologia , Ultrassonografia Pré-NatalRESUMO
Short-rib polydactyly (SRP) syndrome type III, or Verma-Naumoff syndrome, is an autosomal-recessive chondrodysplasia characterized by short ribs, a narrow thorax, short long bones, an abnormal acetabulum, and numerous extraskeletal malformations and is lethal in the perinatal period. Presently, mutations in two genes, IFT80 and DYNC2H1, have been identified as being responsible for SRP type III. Via homozygosity mapping in three affected siblings, a locus for the disease was identified on chromosome 9q34.11, and homozygosity for three missense mutations in WDR34 were found in three independent families, as well as compound heterozygosity for mutations in one family. WDR34 encodes a member of the WD repeat protein family with five WD40 domains, which acts as a TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-κB activation pathway. We showed, through structural modeling, that two of the three mutations altered specific structural domains of WDR34. We found that primary cilia in WDR34 mutant fibroblasts were significantly shorter than normal and had a bulbous tip. This report expands on the pathogenesis of SRP type III and demonstrates that a regulator of the NF-κB activation pathway is involved in the pathogenesis of the skeletal ciliopathies.
Assuntos
Proteínas de Transporte/genética , Cílios/genética , Síndrome de Ellis-Van Creveld/genética , NF-kappa B/metabolismo , Síndrome de Costela Curta e Polidactilia/genética , Transdução de Sinais , Proteínas de Transporte/metabolismo , Cílios/patologia , Dineínas do Citoplasma/genética , Síndrome de Ellis-Van Creveld/patologia , Fibroblastos , Heterozigoto , Homozigoto , Humanos , Recém-Nascido , Masculino , Mutação , Mutação de Sentido Incorreto , Costelas/anormalidades , Costelas/patologia , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
Defects of ciliogenesis have been implicated in a wide range of human phenotypes and play a crucial role in signal transduction and cell-cycle coordination. We used homozygosity mapping in two families with autosomal-recessive short-rib polydactyly syndrome Majewski type to identify mutations in NEK1 as an underlying cause of this lethal osteochondrodysplasia. NEK1 encodes a serine/threonine kinase with proposed function in DNA double-strand repair, neuronal development, and coordination of cell-cycle-associated ciliogenesis. We found that absence of functional full-length NEK1 severely reduces cilia number and alters ciliar morphology in vivo. We further substantiate a proposed digenic diallelic inheritance of ciliopathies by the identification of heterozygous mutations in NEK1 and DYNC2H1 in an additional family. Notably, these findings not only increase the broad spectrum of ciliar disorders, but suggest a correlation between the degree of defective microtubule or centriole elongation and organization and the severity of the resulting phenotype.
Assuntos
Proteínas de Ciclo Celular/genética , Cílios/genética , Mutação , Proteínas Serina-Treonina Quinases/genética , Síndrome de Costela Curta e Polidactilia/genética , Mapeamento Cromossômico , Cílios/fisiologia , Dineínas do Citoplasma/genética , Reparo do DNA/genética , Feminino , Genes Recessivos , Heterozigoto , Humanos , Masculino , Quinase 1 Relacionada a NIMA , Fenótipo , Radiografia , Análise de Sequência de DNA , Índice de Gravidade de Doença , Síndrome de Costela Curta e Polidactilia/diagnóstico por imagem , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
IFT80, a protein component of intraflagellar transport (IFT) complex B, is required for the formation, maintenance and functionality of cilia. Mutations in IFT80 cause Jeune asphyxiating thoracic dystrophy (JATD) and short rib polydactyly (SRP) type III. Both diseases are autosomal recessive chondrodysplasias and share clinical and radiological similarities, including shortening of the long bones and constriction of the thoracic cage. A murine Ift80 gene-trap line was used to investigate the role of Ift80 during development. The homozygote appears hypomorphic rather than a true null due to low level wild-type transcript production by alternative splicing around the gene-trap cassette. Hypomorphic levels of Ift80 result in embryonic lethality highlighting a key role for Ift80 in development. In rare cases, gene-trap homozygotes survive to postnatal stages and phenocopy both JATD and SRP type III by exhibiting growth retardation, shortening of the long bones, constriction of the ribcage and polydactyly. Mouse embryonic fibroblasts made from this line showed a significant reduction in hedgehog pathway activation in response to Hedgehog analog treatment. This defective signalling was not accompanied by the loss or malformation of cilia as seen in some knockout models of other IFT component genes. Phenotypes indicative of defects in cilia structure or function such as situs inversus, cystic renal disease and retinal degeneration were not observed in this line. These data suggest that there is an absolute requirement for Ift80 in hedgehog signalling, but low level expression permits ciliogenesis indicating separate but linked roles for this protein in formation and function.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas Hedgehog/metabolismo , Síndrome de Costela Curta e Polidactilia/metabolismo , Transdução de Sinais , Animais , Proteínas de Transporte/genética , Células Cultivadas , Cílios , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibroblastos/patologia , Proteínas Hedgehog/genética , Humanos , Camundongos , Camundongos Mutantes , Síndrome de Costela Curta e Polidactilia/genética , Síndrome de Costela Curta e Polidactilia/patologia , Transcrição GênicaRESUMO
We present a case of short-rib polydactyly syndrome (SRPs) type 3 in which accurate prenatal diagnosis was feasible using both ultrasonography and 3D-CT. SRP encompass a heterogeneous group of lethal skeletal dysplasias. However, the phenotypes overlap with those of nonlethal skeletal dysplasias (i.e. Ellis-van Creveld syndrome and Jeune syndrome). As accurate prenatal diagnosis of SRP is helpful for parents, we used 3D-CT in the early third trimester to examine a fetus suggested to have phenotypes of 'short-rib dysplasia group' on ultrasonography. 3D-CT showed mild modification of the vertebral bodies, small ilia with horizontal acetabula and triangular partial ossification defects, and subtle metaphyseal irregularities of the femora. These CT findings and an extensive literature search regarding the phenotypes of various diseases categorized as short-rib dysplasia group led to a correct prenatal diagnosis of SRP type 3. This case exemplified the usefulness of 3D-CT for the precise prenatal diagnosis of skeletal dysplasias.
Assuntos
Doenças Fetais/diagnóstico por imagem , Diagnóstico Pré-Natal , Tomografia Computadorizada Espiral , Adulto , Diagnóstico Diferencial , Feminino , Doenças Fetais/patologia , Humanos , Gravidez , Síndrome de Costela Curta e Polidactilia/diagnóstico por imagem , Síndrome de Costela Curta e Polidactilia/patologia , UltrassonografiaRESUMO
BACKGROUND: The lethal group of short-rib polydactyly (SRP) includes type I (Saldino-Noonan; MIM 263530), type II (Majewski; MIM 263520), type III (Verma-Naumoff; MIM 263510) and type IV (Beemer-Langer; MIM 269860). Jeune and Ellis-van Creveld dysplasias also used to be classified in the SRP group. Recently, mutations in a gene encoding a protein involved in intraflagellar transport, IFT80, have been identified in 3/39 patients with Jeune dysplasia but no extraskeletal manifestation. METHODS: Because of clinical and radiological similarities between Jeune dysplasia and the other lethal types of SRP, the authors decided to investigate IFT80 in a cohort of fetuses with the lethal forms of SRP (Majewski, Verma-Naumoff and Beemer-Langer) and antenatally diagnosed cases of Jeune dysplasia. Fifteen fetuses were identified. A double-molecular approach was adopted. For consanguineous families and for those with recurrent sibs, a haplotype analysis around the gene locus was first performed, and, for the others, all the coding exons of IFT80 were directly sequenced. RESULTS: Using the haplotype approach for two families, the authors excluded the IFT80 region as a candidate for them. Direct sequencing of IFT80 in the other 13 cases showed a G-to-C transversion in exon 8 (G241R) in only one SRP case closely related to the type III phenotype. CONCLUSIONS: The findings show that mutations in IFT80 can also be responsible for a lethal form of SRP and provide the molecular basis for the Jeune-Verma-Naumoff dysplasia spectrum.
Assuntos
Proteínas de Transporte/genética , Fenótipo , Sequência de Bases , Síndrome de Ellis-Van Creveld/genética , Síndrome de Ellis-Van Creveld/patologia , Feto , Marcadores Genéticos/genética , Haplótipos/genética , Humanos , Dados de Sequência Molecular , Linhagem , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Síndrome de Costela Curta e Polidactilia/genética , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
Majewski Osteodysplastic Primordial Dwarfism, Type II (MOPD II) is a rare, autosomal recessive disorder. Features include severe intrauterine growth retardation (IUGR), poor postnatal growth (adult stature approximately 100 cm), severe microcephaly, skeletal dysplasia, characteristic facial features, and normal or near normal intelligence. An Institutional Review Board (IRB) approved registry was created and currently follows 25 patients with a diagnosis of MOPD II. Based on previous studies, a neurovascular screening program was implemented and 13 (52%) of these patients have been found to have cerebral neurovascular abnormalities including moyamoya angiopathy and/or intracranial aneurysms. The typical moyamoya pathogenesis begins with vessel narrowing in the supraclinoid internal carotid artery, anterior cerebral (A1) or middle cerebral (M1) artery segments. The narrowing may predominate initially on one side, progresses to bilateral stenosis, with subsequent occlusion of the vessels and collateral formation. We present four patients who, on neurovascular screening, were found to have cerebrovascular changes. Two were asymptomatic, one presented with a severe headache and projectile vomiting related to a ruptured aneurysm, and one presented after an apparent decline in cognitive functioning. Analysis of the registry suggests screening for moyamoya disease be performed at the time of MOPD II diagnosis and at least every 12-18 months using MRA or computerized tomographic angiography (CTA). We believe this is imperative. If diagnosed early enough, re-vascularization and aneurysm treatment in skilled hands can be performed safely and prevent or minimize long-term sequelae in this population. Emergent evaluation is also needed when other neurologic or cardiac symptoms are present.
Assuntos
Nanismo/complicações , Síndrome de Costela Curta e Polidactilia/complicações , Doenças Vasculares/complicações , Doenças Vasculares/patologia , Adolescente , Criança , Pré-Escolar , Constrição Patológica/complicações , Angiografia Coronária , Nanismo/patologia , Humanos , Lactente , Angiografia por Ressonância Magnética , Masculino , Fenótipo , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
The short rib-polydactyly (SRP) group are lethal skeletal dysplasias with an autosomal recessive inheritance pattern that can be distinguished on radiological and histological grounds. We report on two consecutive pregnancies complicated by a SRP syndrome with acromesomelic hypomineralization and campomelia that cannot be definitely categorized, yet possesses features of this group of conditions. The skeletal changes observed in both cases included markedly shortened ribs, shortened humeri and femora, limb bowing, absent ossification of the radii, ulnae, tibiae and fibulae, as well as the bony elements of the hands and feet, hypoplastic scapulae and peritoneal calcifications. In one case, the pancreas was abnormal in shape, without a tail and the spleen was not identified. Ectopic splenic tissue and intestinal malrotation were identified and were suggestive of a laterality disorder. Whether these two cases should be considered an atypical form of SRP cannot be completely resolved at this present time and will need to wait on further progress in molecular testing.
Assuntos
Anormalidades Múltiplas/patologia , Calcinose/patologia , Deformidades Congênitas dos Membros/patologia , Osteocondrodisplasias/patologia , Polidactilia/patologia , Complicações na Gravidez , Síndrome de Costela Curta e Polidactilia/patologia , Adulto , Osso e Ossos/anormalidades , Osso e Ossos/diagnóstico por imagem , Feminino , Humanos , Masculino , Gravidez , Radiografia , IrmãosRESUMO
This case report describes the neuropathological findings in an autopsy case of short rib-polydactyly syndrome (SRPS). The patient was a Japanese female neonate who was born at 35 weeks of gestation and died soon after birth due to severe cardiopulmonary insufficiency. Clinical and radiological findings were most consistent with SRPS type I (Saldino-Noonan type). General autopsy findings included situs inversus, persistent truncus arteriosus and endocardial cushion defect, hypoplastic lungs and adrenal glands, and vaginal atresia. Fixed brain weight was 330 g. Three different categories of pathological changes were detected in the brain. These were as follows: (1) multiple cyst formation in the parenchyma, (2) primary malformations of the nervous and mesenchymal tissues, and (3) deposition of an unusual substance in the cerebral white matter. The multiple cysts or cavities in the parenchyma may be due to severe hypoxic-ischemic insults related to the congenital heart anomaly. The primary malformations were summarized as follows: (1) capillary telangiectasia of the pia mater and choroid plexus, (2) olfactory dysplasia with asymmetry, (3) focal cortical dysplasia in the frontal lobe and cerebellum, (4) olivary dysplasia, and (5) enlargement of the posterior part of the lateral ventricle. Dysplastic changes of the nervous tissue can be classified into the group of neuronal migration disorders. Although biochemical properties of the unknown substance were not determined, it is considered to be some product derived from an inborn error of metabolism. Morphological data of SRPS is still scarce, and pathognomonic changes have not yet been elucidated. The present data suggests that coexistence of the nervous and mesenchymal malformations may be highly characteristic of SRPS.
Assuntos
Encéfalo/patologia , Exostose Múltipla Hereditária/patologia , Doenças do Prematuro/patologia , Síndrome de Costela Curta e Polidactilia/patologia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Recém-Nascido PrematuroAssuntos
Síndrome de Costela Curta e Polidactilia/diagnóstico , Ultrassonografia Pré-Natal , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/embriologia , Anormalidades Múltiplas/patologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Síndrome de Costela Curta e Polidactilia/diagnóstico por imagem , Síndrome de Costela Curta e Polidactilia/embriologia , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
INTRODUCTION: Short rib-polydactyly syndrome (SRPD) is an autosomal recessive, lethal skeletal dysplasia. It is characterized by short limb dwarfism, short ribs with thoracic hypoplasia, polydactyly, and multiple anomalies of major organs. CASE REPORT: We report a case of SRPD subtype II (Majewski) that was detected in the 36th week of gestation, showing hydropic change, narrow thorax, shortened limbs, protuberant abdomen, micromelia, polydactyly and extremely low set ears, depressed nasal bridge, and cleft palate. The family was informed of the fatal outcome of the condition. Delivery was induced, and the baby died just after the birth. DISCUSSION: Prenatal diagnosis is established with postmortem radiographic and pathologic examinations.
Assuntos
Síndrome de Costela Curta e Polidactilia/diagnóstico , Ultrassonografia Pré-Natal , Adulto , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Síndrome de Costela Curta e Polidactilia/diagnóstico por imagem , Síndrome de Costela Curta e Polidactilia/patologiaRESUMO
A description of the clinical features of Majewski osteodysplastic primordial dwarfism type II (MOPD II) is presented based on 58 affected individuals (27 from the literature and 31 previously unreported cases). The remarkable features of MOPD II are: severe intrauterine growth retardation (IUGR), severe postnatal growth retardation; relatively proportionate head size at birth which progresses to true and disproportionate microcephaly; progressive disproportion of the short stature secondary to shortening of the distal and middle segments of the limbs; a progressive bony dysplasia with metaphyseal changes in the limbs; epiphyseal delay; progressive loose-jointedness with occasional dislocation or subluxation of the knees, radial heads, and hips; unusual facial features including a prominent nose, eyes which appear prominent in infancy and early childhood, ears which are proportionate, mildly dysplastic and usually missing the lobule; a high squeaky voice; abnormally, small, and often dysplastic or missing dentition; a pleasant, outgoing, sociable personality; and autosomal recessive inheritance. Far-sightedness, scoliosis, unusual pigmentation, and truncal obesity often develop with time. Some individuals seem to have increased susceptibility to infections. A number of affected individuals have developed dilation of the CNS arteries variously described as aneurysms and Moya Moya disease. These vascular changes can be life threatening, even in early years because of rupture, CNS hemorrhage, and strokes. There is variability between affected individuals even within the same family.