Displasia tanatofórica tipo II, una entidad congénita inusual. Reporte de caso / Thanatophoric dysplasia type 2, an unusual congenital disease - Case Report

Resumen La displasia tanatofórica es un defecto congènito inusual y esporádico cuyo desenlace es la muerte intrauterina o pocos días después del nacimiento. Su aparición se ha descrito en 0,2-0,5 casos de cada 10.000 nacidos vivos, y depende de la mutación del receptor del factor de crecimiento fibroblasto-3. Cuenta con dos presentaciones clínicas: tipo I y tipo II; esta última es menos frecuente y se caracteriza por el hallazgo de cráneo en hoja de trébol y micromelia con fémures rectos. A continuación, se presenta el caso de una joven multípara con hallazgo en la primera ecografía del embarazo de feto con acortamiento general de las extremidades y disminución de la osificación general, sugestiva de displasia tanatofórica tipo II, que resultó en la interrupción voluntaria del embarazo. El diagnóstico temprano en la gestación es importante para orientar la práctica médica con base en el mal pronóstico del padecimiento de esta patología.

Abstract Thanatophoric dysplasia is an unusual and sporadic congenital defect whose outcome is intrauterine death or a few days after birth. Its appearance has been described in 0.2-0.5 cases of every 10,000 live births and depends on the mutation of the fibroblast growth factor receptor-3. It exhibits two clinical presentations, of these, the so-called type II is less frequent and is characterized by the finding of a cloverleaf skull and micromelia with straight femurs. The following is the case of a young multiparous pregnant woman with a finding in her first ultrasound of fetus pregnancy with general shortening of the limbs and decreased general ossification, suggestive of thanatophoric dysplasia type II, which resulted in the voluntary termination of pregnancy. Early diagnosis in pregnancy is important in order to guide medical practice based on the poor prognosis of suffering from this pathology.

Tracheobronchopathia Osteochondroplastica and Lung Carcinoma: A Rare Combination

Tracheobronchopathia osteochondroplastica is a rare benign idiopathic disorder of unknown cause affecting the large airways. Bronchoscopy and computed tomography (CT) of the thorax establish the diagnosis, but biopsy is confirmatory. We describe a case of tracheobronchopathia osteochondroplastica, rarely associated with lung cancer. There should be a high index of suspicion of tracheobronchopathia osteochondroplastica, especially in patients with malignancy; as it can easily be missed in a patient with lung malignancy.

Genetic analysis of a pedigree of DYNC2H1 gene variation-caused short rib polydactyly syndrome type Ⅲ / 中华围产医学杂志

This paper reported the genetic analysis of a pedigree in which three affected fetuses with short limbs were revealed by first-trimester ultrasonography in three consecutive pregnancies. Tissues of the second aborted fetus were collected and analyzed by chromosome karyotype analysis and whole exome sequencing. The results indicated compound heterozygous mutations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene. Real-time fluorescence quantitative polymerase chain reaction and Sanger sequencing further confirmed that the two variants were inherited from the father and the mother with normal phenotypes, respectively. EX64-EX83 Del was a likely pathogenic variant and c.8190G>T was a variant of uncertain significance. Based on the above results and the medical history, it was highly suspected that the fetus had autosomal recessive short rib polydactyly syndrome type Ⅲ caused by compound heterozygous variants. Real-time fluorescent quantitative polymerase chain reaction and Sanger sequencing results of the third aborted fetus were consistent with the second fetus. Given the same phenotypes of fetuses in the second and third pregnancy, it was strongly suggested that the heterozygous variations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene were the pathogenic variants in this pedigree.

Afectación respiratoria en paciente con acrodisostosis: una asociación infrecuente de una enfermedad rara / Respiratory impairment in a patient with acrodysostosis: A rare association of an uncommon pathology

La acrodisostosis es una displasia esquelética rara, de herencia autosómica dominante, que se caracteriza por la presencia de disostosis facial y periférica, talla baja y diferentes grados de obesidad. La acrodisostosis de tipo 1, secundaria a la mutación heterocigota en el gen PRKAR1A (17q24.2), se caracteriza por la asociación de resistencia hormonal múltiple con anomalías esqueléticas. Su incidencia está infradiagnosticada debido a que comparte rasgos clínicos y de laboratorio con otras entidades como el seudohipoparatiroidismo. Presentamos el caso de una niña de 8 años, con acrodisostosis tipo 1, confirmada mediante estudio genético. Además del fenotipo característico descrito, la talla baja y la resistencia hormonal, la paciente presentó una afectación progresiva de la función pulmonar: un patrón pulmonar obstructivo no reversible. En la literatura revisada, no se han encontrado otros casos que describan esta asociación entre acrodisostosis y afectación respiratoria.

Acrodysostosis is a rare skeletal displasia, of autosomal dominant inheritance, characterized by the presence of facial and peripheral dysostosis, short stature and obesity. Type 1 acrodysostosis is secondary to a mutation in the PRKAR1A (17q24.2) gene, which results in multi hormonal resistance and skeletal anomalities. This syndrome is under-diagnosed as it shares analytical and clinical characteristics with other entities, such as pseudohypoparathyroidism. We report the case of an eight-year-old girl with genetically confirmed type 1 acrodysostosis. In addition to the characteristic phenotype described, the short stature and the hormonal resistance, the patient suffered a progressive lung function deterioration: an irreversible pulmonary obstructive pattern. We have not found in previous literature cases reporting an association between acrodysostosis and lung function impairement.

Clinical characteristics and pathogenic gene analysis in a large pedigree with multiple epiphyseal dysplasia / 中华骨科杂志

Objective@#To provide experimental evidence for genetic counseling and prenatal molecular diagnosis by analyzing the clinical characteristics and screening for pathogenic genes of a five-generation suspected multiple epiphyseal dysplasia (MED) family (17 patients).@*Methods@#The family members' medical history, general physical examination and hip joint X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA were extracted from these samples. The exons of clinical genes from probands' DNA were sequenced by High throughput sequencing method. Next Gene software was used to compare and analyze the sequence and INGENUITY software was further used to annotate the mutations in order to find the pathogenic mutations in probands. The suspicious mutations were confirmed in pedigree members by PCR and Sanger sequencing.@*Results@#The family consisted of 5 generations and 38 members. Pedigree analysis was consistent with autosomal dominant inheritance. There were 17 patients in the family, and their clinical manifestations showed abnormal walking posture in childhood, pain in hip and knee joints, and typical pathological changes of epiphyseal dysplasia on X-ray. Cartilage oligomeric matrix protein (COMP) gene c.1153G>A (p.Asp385Asn) missense heterozygous mutation was screened in proband, which was genotypically and phenotypically segregated in the pedigree.@*Conclusion@#A missense mutation of the comp gene has been identified in a pedigree affected with MED which was the first reported in a big family. Our result is conducive to the further diagnosis and treatment and also provides a molecular basisfor the future prenatal diagnosis.

Clinical characteristics and pathogenic gene analysis in a large pedigree with multiple epiphyseal dysplasia / 中华骨科杂志

Objective To provide experimental evidence for genetic counseling and prenatal molecular diagnosis by analyzing the clinical characteristics and screening for pathogenic genes of a five-generation suspected multiple epiphyseal dysplasia (MED) family (17 patients).Methods The family members' medical history,general physical examination and hip joint X-ray examination were collected.Peripheral blood samples of the family members were collected and DNA were extracted from these samples.The exons of clinical genes from probands' DNA were sequenced by High throughput sequencing method.Next Gene software was used to compare and analyze the sequence and INGENUITY software was further used to annotate the mutations in order to find the pathogenic mutations in probands.The suspicious mutations were confirmed in pedigree members by PCR and Sanger sequencing.Results The family consisted of 5 generations and 38 members.Pedigree analysis was consistent with autosomal dominant inheritance.There were 17 patients in the family,and their clinical manifestations showed abnormal walking posture in childhood,pain in hip and knee joints,and typical pathological changes of epiphyseal dysplasia on X-ray.Cartilage oligomeric matrix protein (COMP) gene c.1153G ＞ A (p.Asp385Asn) missense heterozygous mutation was screened in proband,which was genotypically and phenotypically segregated in the pedigree.Conclusion A missense mutation of the comp gene has been identified in a pedigree affected with MED which was the first reported in a big family.Our result is conducive to the further diagnosis and treatment and also provides a molecular basisfor the future prenatal diagnosis.

Manejo quirúrgico de la duplicación patelar bilateral en displasia epifisiaria múltiple recesiva. Reporte de caso / Surgical management of bilateral duplication of the patella in multiple recessive epiphyseal dysplasia. A case report

Introducción La displasia epifisiaria múltiple (DEM) es una enfermedad poco frecuente y con gran variedad clínica y se caracteriza por deformidades en las articulaciones, dolor, y trastornos de la marcha. La duplicación patelar se asocia con DEM recesiva y consiste en dos segmentos patelares escalonados separados por tejido blando entre ellos. Caso clínico Paciente masculino de 30 años con cuadro clínico de DEM recesiva con duplicación patelar, presenta dolor crónico bilateral de cadera y rodilla, y trastorno de la marcha. Tras el examen físico, se evidenció derrame articular, dificultad para la flexión de las rodillas y un cuerpo libre intra-articular bilateral. Se identificaron dos segmentos patelares, displasia acetabular y de cabeza femoral bilateral con imágenes diagnósticas. El manejo quirúrgico de la duplicación patelar fue resección de los segmentos óseos accesorios, conduciendo a un resultado clínico satisfactorio al año de seguimiento. Discusión Aunque no se realiza el diagnóstico genético de la DEM, nuestro paciente presenta las características fenotípicas y radiológicas de esta entidad. Para la duplicación patelar, se realizó la resección de las patelas accesorias, considerando el alto riesgo de no unión. Sin embargo, existen varios reportes donde unieron los dos segmentos patelares, pero principalmente en niños. Este es el primer reporte publicado sobre el manejo quirúrgico de esta patología en Colombia. La duplicación patelar puede manejarse con éxito mediante la resección de la patela accesoria en adultos. Aunque los hallazgos imagenológicos son muy sugestivos de esta patología, se requiere un adecuado examen físico para evitar un diagnóstico equivoco y tardío.

Background Multiple epiphyseal dysplasia (MED) is a rare disease with a great clinical variation, and is characterised by deformities in the joints, pain, and gait disorders. Duplication of the patella is associated with recessive MED, and consists of two staggered patellar segments separated by soft tissue between them. Clinical case A 30-years-old male patient with a clinical manifestation of recessive MED with duplication of the patella, chronic bilateral hip and knee pain, as well as gait disorder. After the physical examination, joint effusion, difficulty in flexing the knees, and a bilateral intra-articular free body were evident. Two patellar segments, acetabular dysplasia and bilateral femoral head, were identified with diagnostic imaging. The surgical management of duplication of the patella was resection of the accessory bone segments, leading to a satisfactory clinical result at one year of follow-up. Discussion Although the genetic diagnosis of the MED was not made, our patient presented with the phenotypic and radiological characteristics of this disease. For duplication of the patella, the accessory patella resection was performed, considering the high risk of non-union. However, there are several reports where the two patellar segments are joined; but mainly in children. This is the first report published about the surgical management of this pathology in Colombia. Duplication of the patella can be managed successfully by resecting accessory patella in adults. Although the imaging findings are very suggestive of this pathology, an adequate physical examination is required to avoid a false and late diagnosis.

Prenatal diagnosis of three cases of fetal skeletal dysplasia resulting from loss of heterozigosity of short stature homeobox gene / 中华围产医学杂志

Objective To analyze the genotype-phenotype correlation in fetal skeletal dysplasia,and to investigate the methods of prenatal diagnosis and genetic counseling.Methods From May 2016 to November 2017,three gravidas whose fetuses were diagnosed with short stature homeobox (SHOX) gene deficiency were recruited from those receiving invasive prenatal diagnosis and single nucleotide polymorphismarray (SNP-array) due to fetal structural abnormalities detected by prenatal ultrasound scan in Shanghai First Maternity and Infant Hospital,Tongji University School of Medicine.Fetus 1 and 3 were singleton pregnancies and fetus 2 was twin pregnancy.Amniotic fluid cells were isolated and analyzed by karyotyping and SNP-array.Peripheral blood samples were collected from their parents and also analyzed by SNP-array.Results All three fetuses were diagnosed with fetal skeletal dysplasia based on second trimester ultrasound findings showing the lengths of femora,humeri,tibiae,fibulae,ulnae and radii length below the 5th percentile of corresponding gestational age.Karyotypes of the three fetuses were normal.SNP-array examination showed that each case had 1 to 2.5 Mb deletion in the pseudoautosomal region of the short arms of sex chromosomes,including SHOX gene.Their skeletal dysplasia were all caused by SHOX haploinsufficiency.Microdeletions of fetus 1 and 3 were inherited from their mothers,while that of fetus 2 was inherited from the father.After genetic counseling,two singleton gravidas decided to terminate their pregnancies and the twin pregnant one underwent selective reduction.Conclusion Prenatal ultrasound,in combination with SNP-array,offers fast and efficient detection of fetal skeletal dysplasia due to SHOX gene deficiency.

Displasia epifisaria con falanges en forma de ángel: Caso clínico / Angel-shaped phalango-epiphyseal dysplasia: Case report

Se describe una patología de aparición poco frecuente y esporádica que se caracteriza por deformidad en cuello de cisne en las manos, artrosis de cadera en la adultez, retardo en la edad ósea y malformaciones de las falanges medias, en forma de ángel. El paciente es un niño de 4 años de edad que sufrió un traumatismo de mano, por lo cual se le realizó una radiografía donde se observaron falanges con forma de ángel. A partir de este hallazgo, se obtuvieron otras radiografías y se diagnosticó una displasia epifisaria con falanges en forma de ángel. A raíz de este diagnóstico en el niño y de consultas con el Servicio de Genética, se diagnosticó el mismo síndrome en la madre.

We describe a rare and sporadic condition, characterized by swan neck deformity in hands, hip osteoarthritis in adulthood and malformations of the middle phalanges with an angel shape. The patient is a 4 year old boy who suffered hand trauma and on x-ray examination he was diagnosed with angel-shaped phalango-epiphyseal dysplasia. Based on this diagnosis, his mother, who suffered from constant pain in her hips and lower limbs, was diagnosed with this syndrome as well.

Primary outcomes of femoral head reduction osteotomy for coxa magna or coxa plana / 中华骨科杂志

Objective To investigate the clinical efficiency and safety of femoral head reduction osteotomy for young patients with coxa magna or coxa plana.Methods Between June 2012 and September 2015,the clinical characteristics of 12 patients (13 hips) with coxa magna or coxa plana who underwent femoral head reduction osteotomy were analyzed retrospectively.There were 6 males (7 hips) and 6 females (6 hips) with average age 18.1 years (range,10-25 years).The etiology of the femoral head deformity was multiple epiphyseal dysplasia in 6 hips and Legg-Calvé-Perthes sequela in 7 hips.The head reduction osteotomy was conducted through the surgical hip dislocation approach combined with extended retinacular soft-tissue flap extending technique.All patients underwent simultaneous periacetabular osteotomy and relative lengthening of the femoral neck,of which four also underwent proximal femur derotational osteotomy.All patients received the standardized rehabilitation procedures.The postoperative complications,gaits,the range of motion (ROM) of the hip,Harris hip scores,iHOT scores and VAS were analyzed postoperatively.In addition,the lateral center-edge (LCE) angle,sphericity index and coverage rate of femoral head were assessed as well.Results The average follow-up duration was 28.8 months (range,12-45 months).All patients achieved osteotomy healing of the femoral head and greater trochanter with average healing time 3.7 months (range,3-7 months).Nine of 12 patients had significant gaits improvement.The Harris hip scores (81.08± 12.36 vs.88.38 ± 8.96,t=2.41,P=0.033),iHOT score (51.90± 15.07 vs.67.69±8.70,t=3.63,P=0.003),LCE angle (-1.82°±16.57° vs.36.02°±7.72°,t=10.52,P=0.000),sphericity index of anteroposterior pelvic radiographs (71.08％± 10.32％ vs.81.22％±8.61％,t=7.17,P=0.000) and the coverage index (48.79％±11.85％ vs.87.46％± 10.44％,t=8.56,P=0.000) were all significantly improved when compared to those preoperatively.The VAS score (4.46± 2.37 vs.1.23±0.93,t=4.25,P=0.001) was significantly decreased when compared with that preoperatively.However,for the sphericity index of 65° false profile (78.96％± 10.39％ vs.80.36％±8.42％,t=0.411,P=0.688) and the average hip ROM (264.62°± 32.05° vs.255.00°±40.31°,t=0.89,P=0.391),they did not achieve statistical significant difference.One case of femoral head necrosis site was localized at the lateral-superior part of femoral head,and there was no progression after 3 years follow-up.Moreover,no revision or total hip arthroplasty were observed due to other complications (osteoarthritis,hip pain or non-union).Conclusion The femoral head reduction osteotomy can correct deformity,improve femoral head sphericity,relieve pain and improve gaits and hip function.This procedure leads to satisfied clinical outcomes for patients with coxa magna or coxa plana in early follow-up.

Rare case of nephrotic syndrome: Schimke syndrome / Caso raro de síndrome nefrótica: síndrome de Schimke

Abstract Schimke syndrome corresponds to dysplasia of bone and immunity, associated with progressive renal disease secondary to nephrotic syndrome cortico-resistant, with possible other abnormalities such as hypothyroidism and blond marrow aplasia. It is a rare genetic disorder, with few reports in the literature. The most frequent renal involvement is nephrotic syndrome with focal segmental glomerulosclerosis and progressive renal failure. The objective of this study was to report a case of Schimke syndrome, diagnostic investigation and management of the case.

Resumo A síndrome Schimke corresponde à displasia imuno-óssea, associada à doença renal progressiva secundária à síndrome nefrótica córtico-resistente, podendo haver outras anormalidades como hipotireoidismo e aplasia de medula óssea. Trata-se de uma patologia genética rara, com poucos relatos na literatura. O acometimento renal mais frequente é uma síndrome nefrótica por glomeruloesclerose segmentar e focal e falência renal progressiva. O objetivo deste estudo foi relatar um caso de síndrome de Schimke, investigação diagnóstica e condução do caso.

Displasia cefaloesquelética (Síndrome de Taybi-Linder): Presentación de un caso y consideraciones anestésicas / Cephaloskeletal dysplasia (Taybi-Linder syndrome): Case report and anesthetic considerations

Introduction: Microcephalic osteodysplastic primordial dwarfism (or Taybi-Linder syndrome) is a rare disease characterized by bone and central nervous system malformations, in addition to intrauterine retardation. Case presentation: 20-year-old patient operated on for adhesiolysis and enteropexy due to bowel obstruction from post surgical adhesions. Conclusion: The anesthetic considerations in these patients include the potential airway impairment secondary to facial malformations and neurological complications, primarily seizures.

Introducción: El enanismo microcefálico osteodisplásico primario (o síndrome de Taybi- Linder) es una infrecuente enfermedad caracterizada por malformaciones óseas, del sistema nervioso central y crecimiento intrauterino retardado. Presentación del caso: Paciente de 20 años intervenida de adhesiolisis y pexia intestinal por un cuadro de obstrucción intestinal por bridas postquirúrgicas. Conclusión: Como consideraciones anestésicas de estos pacientes destacamos las posibles alteraciones de la vía aérea secundarias a las malformaciones faciales y las complicaciones neurológicas, principalmente crisis convulsivas.

Condrodisplasia metafisaria tipo Schmid: un caso de presentación familiar / Schmid type metaphyseal chondrodysplasia: a case of familial presentation

Resumen: dentro de las displasias óseas hay cuadros clínicos que hacen parte de las denominadas condrodisplasias metafisarias, conocidas también como disostosis metafisarias, las cuales presentan mínimas diferencias entre sí, lo que las hace susceptibles de ser confundidas con otros cuadros clínicos como la acondroplasia y el raquitismo. En este artículo se presenta un caso clínico de condrodisplasiametafisaria tipo Schmid de un paciente de Popayán, Colombia, al igual que algunas consideracionessobre las principales características clínicas, radiológicas, de diagnóstico y tipo de herencia de esta enfermedad. El caso clínico corresponde a un paciente de género masculino de 23 meses de edad, en quien se inician estudios por la presencia de talla baja desproporcionada. Los resultados mostraron coxa vara, genu varo y extremidades cortas, con un fenotipo similar en la madre y el abuelo materno. Las radiografías evidencian la presencia de irregularidad con “deshilachamiento” de las metáfisis de huesos largos; además, ensanchamiento y esclerosis en las metáfisis proximales de ambos fémur. La meta final es ser confirmado por medio de pruebas genéticas. En conclusión, las condrodisplasias metafisarias, especialmente la tipo Schmid, son enfermedades caracterizadas por talla baja y hallazgos radiológicos especiales, dados principalmente por el compromiso metafisario a nivel de los huesos largos, que en conjunto con las características fenotípicas pueden conducir a la sospecha e identificación de este tipo de patología.

Abstract: between the dysplastic bone pathologies there are some medical conditions that belong to so-called metaphyseal chondrodysplasias, also known as metaphyseal dysostosis. These differ slightly from each other, making them capable of being confused with other medical conditions such as achondroplasia and rickets. This article presents a case of Schmid type metaphyseal chondrodysplasiafrom Popayan, Colombia, as well as some considerations about the main clinical characteristics, radiological, diagnosis, and type of inheritance of this disease. The clinical case corresponds to a male patient, 23 months old, who was studied by the presence of disproportionate short stature. Findings showed coxa vara, genu varus, and short limbs, with similar phenotype to the mother and maternal grandfather. The radiological images showed the presence of irregularity with ®fraying¼ of the metaphysis of long bones, in addition to widening and sclerosis in the proximal metaphysis of both femurs. The ultimate goal is to be confirmed by genetic testing. In conclusion, the metaphyseal chondrodysplasias, especially Schmid type, are diseases characterized by short stature and by special radiological findings, mainly given by the metaphyseal affectation of long bones, which together with the phenotypic characteristics may lead to the suspicion and identification of this disease.Keywords: Schmid type metaphyseal chondrodysplasia, osteochondrodysplasias, collagen type.

What is new in genetics and osteogenesis imperfecta classification? / O que há de novo em genética e classificação de osteogênese imperfeita?

OBJECTIVE: Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. SOURCES: Literature review in the PubMed and OMIM databases, followed by selection of relevant references. SUMMARY OF THE FINDINGS: In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. CONCLUSIONS: Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference. .

OBJETIVO: Revisão da literatura sobre novos genes relacionados à osteogênese imperfeita (OI) e atualização da sua classificação. FONTE DOS DADOS : Revisão nas bases de dados do PUBMED e OMIM com seleção de referências relevantes. SÍNTESE DOS DADOS: Sillence et al., em 1979, desenvolveram uma classificação dos subtipos de OI baseada em características clínicas e gravidade da doença: OI tipo I, forma leve, comum, com escleras azuladas; OI tipo II, forma perinatal letal; OI tipo III, forma grave e progressivamente deformante com esclera normal; e OI tipo IV, forma de gravidade moderada com esclera normal. Cerca de 90% dos indivíduos com OI são heterozigotos para mutações em COL1A1 e COL1A2, com padrão de herança dominante ou esporádico. A partir de 2006 foram identificadas mutações nos genes CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1 e TMEM38B associadas à OI recessiva e mutação em IFITM5 associada à OI dominante. Mutações em PLS3 foram identificadas recentemente em famílias com osteoporose e fraturas, com padrão de herança ligado ao X. Além da complexidade genética das bases moleculares das OI, extensa variabilidade fenotípica resultante de loci individuais também tem sido documentada. CONCLUSÕES: Face à descoberta de novos genes e à correlação genótipo-fenótipo limitada, o uso de ferramentas de sequenciamento de nova geração torna-se útil no estudo molecular de casos de OI. A recomendação do Grupo de Nosologia da Sociedade Internacional de Displasias Esqueléticas é manter a classificação de Sillence como a forma prototípica e universalmente aceita para classificar o grau de gravidade na OI, e libertá-la de referência ...

Report of a novel mutation in the SLC26A2 gene found in a Colombian adult patient with diastrophic dysplasia / Reporte de una nueva mutación en el gen SLC26A2 en un paciente adulto colombiano con displasia diastrófica

Summary Background. Diastrophic dysplasia is an osteochondrodysplasia belonging to the group of dysplasias caused by mutations in the diastrophic dysplasia sulfate transporter. This sindrome is a micromelic dysplasia with multiple bone deformities of the hands, feet, knees and spine. Objective. Describe the first report of diastrophic displasia in Colombia Materials and methods. In this paper a Colombian adult patient with diastrophic dysplasia whose clinical diagnosis was confirmed at the molecular level is reported. Results. In this first report of diastrophic dysplasia in Colombia we found that the patient was compound heterozygote for the already reported Arg279Trp substitution and an unpublished mutation, a Ser157Thr substitution in the SLC26A2 gene. Conclusion. Bioinformatic analysis on the latter mutation suggested that it could correspond to a deleterious mutation because it is in a highly conserved domain of the sulfate transporter.

Resumen Antecedentes. La displasia diastrófica es una osteocondrodisplasia que pertenece al grupo de las enfermedades genéticas del esqueleto causadas por mutaciones en los transportadores de sulfato. Se presenta como una displasia micromélica con afectación de múltiples huesos y deformidades en manos, pies, rodillas y columna vertebral. Objetivo. Describir el primer reporte de displasia diastrófica en Colombia. Materiales y métodos. Se reporta un adulto colombiano con esta displasia, con confirmación clínica, radiológica y molecular. Resultados. En este primer reporte colombiano, se encontró que la paciente presentó una mutación heterocigota compuesta, de Arg279Trp y Ser157Thr, esta última no reportada previamente, en el gen SLC26A2. Conclusión. El análisis bioinformático de la mutación nueva sugiere que podría corresponder a una mutación deletérea dado que el dominio afectado en el transportador de sulfatos es altamente conservado.

Detection of TRAPPC2 gene mutation in a Chinese pedigree of X-linked spondyloepiphyseal dysplasia tarda / 中华检验医学杂志

Objective To identify the mutation of trafficking protein particle complex 2 (TRAPPC2) gene in a large Chinese pedigree with X-linked spondyloepiphyseal dysplasia tarda by the PCR-based capillary electrophoresis methods.Methods The blood samples were collected from a large Chinese pedigree of three generations with six affected persons with X-SEDT.Four exons comprising the TRAPPC2 gene open reading frame as well as their exor/intron boundaries were analyzed by argrose electrophoresis and bidirectional direct sequencing of PCR products.Fluorescence labeled fragment analysis was performed by capillary electrophoresis.Results A 5-bp deletion mutation of TRAPPC2 gene in exon 5,c.262_266delGACAT (D88del; I89fX12),was identified in the proband and his unaffected mother(a heterozygote) in the Chinese family with X-SEDT,but no other sequence change occurring in exons 3,4 and 6 was detected.The old sister of proband was determined being carriers because she carries the deletion fragment allele of exon 5 PCR product and the young sister being normal individuals because she carries the wild allele of TRAPPC2 gene.Conclusions The mutation c.262_266delGACAT (D88del; I89fX12) of TRAPPC2 gene was firstly reported in Chinese people.The mutation of c.262_266delGACAT (D88del; I89fX12) in TRAPPC2 gene may be the pathologic cause of the patients in the X-SEDT pedigree.Fragment analysis combined with DNA sequencing by capillary electrophoresis method is effective laboratory test in the small deletion mutation analysis and carriers screening in X-SEDT family.

Schwartz-Jampel Syndrome: a paediatric dentistry approach / Síndrome de Schwartz-Jampel: uma abordagem odontopediátrica

Schwartz-Jampel syndrome (SJS) is a rare recessive disorder characterized mainly by myotonia. As the clinical signs and symptoms are manifested in the oromaxillofacial region, paediatric dentists may be first choice of parents that seek information and assistance to their children. A female patient diagnosed with SJS was brought to our clinic for dental treatment with main complain of difficulty on oral hygiene and mastication due to tooth crowding. The treatment included preventive measures, extraction of a supernumerary tooth and the maxillary primary second molars. Furthermore, the patient was referred to orthodontic treatment for correction of tooth crowding. When dealing with children with confirmed diagnosis of SSJ, paediatric dentists should be understand the need of planning the dental treatment considering the characteristics and possible complications associated with the syndrome in order to reduce the risks to patients, especially when surgical procedures are necessary

A síndrome de Schwartz Jampel (SSJ) é uma desordem autossômica recessiva rara, caracterizada principalmente pela miotonia. Desde que alguns dos sinais clínicos e sintomas são manifestados na região oromaxilofacial, o odontopediatra pode ser o primeiro profissional a se deparar com um paciente portador desta síndrome. Um paciente do sexo feminino diagnosticado com SJS procurou a nossa clínica para tratamento dental com queixa principal de dificuldade na realização da higiene oral e mastigação, devido ao mau posicionamento dentário. O tratamento incluiu medidas preventivas, extração de um dente supranumerário e dos segundos molares decíduos e encaminhamento para tratamento ortodôntico. Quando uma criança possui o diagnóstico confirmado para SSJ, o odontopediatra deve ter conhecimento específico para planejar e realizar o tratamento odontológico de forma adequada, considerando as características da síndrome e as possíveis complicações associadas, a fim de reduzir os riscos ao paciente, especialmente quando procedimentos cirúrgicos são necessários.

Síndrome otopalatodigital tipo II, aproximación prenatal y diagnóstico clínico de un caso complejo de displasia ósea / Prenatal diagnosis of otopalatodigital syndrome type 2

El síndrome otopalatodigital tipo 2 (OPD2), es una rara entidad con herencia recesiva ligada al cromosoma X, letal, caracterizada por facies anormales con hipoplasia centrofacial, hipertelorismo ocular, paladar hendido, talla baja, huesos largos curvos, sindactilia en pies y manos y anomalías óseas. Usualmente originadas en mutaciones en el gen de la filamina A (FLNA). Se reporta un caso, con diagnóstico prenatal de osteocondrodisplasia que posteriormente por hallazgos al examen físico y radiológicos del recién nacido se clasifico como síndrome otopalatodigital tipo 2.

Otopalatodigital syndrome, type 2 (OPD2), is a rare entity with recessive heredity linked to the X chromosome, lethal, characterized by abnormal facies, with centro-facial hypoplasia, ocular hypertelorism, cleft palate, low height, curved long bones, syndactyly, and osseous anomalies on feet and hands. It has been recently shown that patients with OPD2 with mutations in the filamin A gene (FLNA), which is also found altered in allelic entities like the OPD1 syndrome, the Melnik-Needles syndrome and frontometaphyseal dysplasia. Herein, we report a case with prenatal osteochondrodysplasia diagnosis that after physical and radiological exam of the newborn was classified as otopalatodigital syndrome type 2.

Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation

The transient receptor potential vanilloid 4 (TRPV4) cation channel, a member of the TRP vanilloid subfamily, is expressed in a broad range of tissues where it participates in the generation of Ca2+ signals and/or depolarization of the membrane potential. Regulation of TRPV4 abundance at the cell surface is critical for osmo- and mechanotransduction. Defects in TRPV4 are the cause of several human diseases, including brachyolmia type 3 (MIM:113500) (also known as brachyrachia or spondylometaphyseal dysplasia Kozlowski type [MIM:118452]), and metatropic dysplasia (MIM:156530) (also called metatropic dwarfism or parastremmatic dwarfism [MIM:168400]). These bone dysplasia mutants are characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the extremities, and contractures of the large joints. These diseases are characterized by a combination of decreased bone density, bowing of the long bones, platyspondyly, and striking irregularities of endochondral ossification with areas of calcific stippling and streaking in radiolucent epiphyses, metaphyses, and apophyses. In this review, we discuss the potential effect of the mutation on the regulation of TRPV4 functions, which are related to human diseases through deviated function. In particular, we emphasize how the constitutive active TRPV4 mutant affects endochondral ossification with a reduced number of hypertrophic chondrocytes and the presence of cartilage islands within the zone of primary mineralization. In addition, we summarize current knowledge about the role of TRPV4 in the pathogenesis of several diseases.