Clinical and molecular genetic analysis of a child with Schmid type metaphyseal chondrodysplasia / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features and genotype of a child with Schmid type metaphyseal chondrodysplasia.@*METHODS@#Clinical data of the child and her parents was collected. The child was subjected to high-throughput sequencing, and candidate variant was verified by Sanger sequencing of her family members.@*RESULTS@#Whole exome sequencing revealed that the child has harbored a heterozygous c.1772G>A (p.C591Y) variant of the COL10A1 gene, which was not found in either of her parents. The variant was not found in the HGMD and ClinVar databases, and was rated as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*CONCLUSION@#The heterozygous c.1772G>A (p.C591Y) variant of the COL10A1 gene probably underlay the Schmid type metaphyseal chondrodysplasia in this child. Genetic testing has facilitated the diagnosis and provided a basis for genetic counselling and prenatal diagnosis for this family. Above finding has also enriched the mutational spectrum of the COL10A1 gene.

Displasia frontometafisaria 2 asociada con deformidad torácica e hipertensión arterial pulmonar: a propósito de un caso y revisión bibliográfica / Frontometaphyseal dysplasia 2 associated with thoracic deformity, and pulmonary arterial hypertension: a case report and review of literature

La displasia frontometafisaria 2 (DFM2) es una enfermedad rara causada por una mutación en el gen MAP3K7. En este artículo, se informa sobre un paciente de 7 años con DFM2 causada por una variante nueva de corte y empalme en MAP3K7. El paciente presenta las características frecuentes de la DFM2, pero algunas nunca antes informadas. No se dispone de una descripción sistemática de las características de las imágenes tomográficas de la DFM2. Describimos ciertas diferencias en las características de la DFM2, la bibliografía publicada y las manifestaciones imagenológicas generales de la DFM2. Este caso resalta la importancia del valor clínico de la tomografía computada (TC) y la renderización de volúmenes (VR) en el diagnóstico de la DFM2. Las características de la DFM2 pueden observarse claramente en los estudios tomográficos, lo que señala la gran importancia de la TC para el diagnóstico y el tratamiento precoces de los pacientes con DFM2.

Frontometaphyseal dysplasia 2 (FMD2) is a rare disease caused by MAP3K7 gene mutation. We report a 7-year-old sporadic patient with FMD2 due to a de novo splicing variant in MAP3K7. He has the common characteristics of FMD2 but also has some characteristics that have never been reported, which increases the clinical phenotype of FMD2. Moreover, no systematic description of the imaging characteristics of FMD2 in computed tomography (CT) is available. In the present work, we found some different features of FMD2, reviewed previous literature, and summarized the general imaging manifestations of FMD2. This case emphasizes the important clinical value of CT and VR in the diagnosis of FMD2. We can clearly find the characteristics of FMD2 by CT examination, indicating its great significance for the prompt diagnosis and treatment of FMD2 patients.

Deformidad de la caja torácica / Chest wall deformity

Resumen Las deformidades de la caja torácica se pueden dividir en dos tipos, las que son productos del desarrollo anormal del pecho en el crecimiento y las congénitas que son las secundarias a una malformación estructural del pecho evidente en el nacimiento. Las malformaciones del desarrollo son las más comunes, como por ejemplo pectus excavatum o pectun carinatum. Las menos comunes son las de tipo congénito: síndrome de Poland, displasia espondilotorácica, displasia espondilocostal, síndrome de Jeune y los defectos de la costilla o el esternón. Las deformidades del pecho de tipo congénita se caracterizan por afectar la relación entre la columna vertebral, la caja torácica y los pulmones. La mayoría de estos pacientes desarrollan un disturbio respiratorio progresivo de tipo restrictivo conocido como Síndrome de Insuficiencia Torácica. Este síndrome se define como la deficiencia de la caja torácica para mantener una respiración normal y sostener el crecimiento fisiológico del pulmón. En este artículo discutiremos varias condiciones que afectan el desarrollo y función de la caja torácica.

Chest wall deformities are divided as an abnormal development during the growth or those secondary to a congenital malformation. The developmental type is the most common: pectus excavatum or pectus carinatum. The less common are the congenital types of chest wall abnormalities: Poland's syndrome, Jeune's syndrome, espondylothoracic dysplasia, espondylocostal dysplasia and defects of the ribs or sternum. The congenital type usually affects the relationship between the spine, rib cage and the lungs. Therefore, many of these patients will develop a progressive respiratory disturbance of restrictive type known as Thoracic Insufficiency Syndrome. Thoracic insufficiency syndrome is defining as a deficiency of the rib cage to maintain a normal respiration and to sustain the physiological growth of the lungs. In this article will discuss several conditions that will affect the development and function of the chest wall.

Síndrome de Grebe: Reporte de un caso / Grebe syndrome. Case report

La condrodisplasia de Grebe es un trastorno raro autosómico recesivo que pertenece al grupo de las osteocondrodisplasias. Clínicamente se caracteriza por un severo dismorfismo con una marcada micromelia y deformidad de las extremidades inferiores y superiores. Conocer este tipo de síndrome orienta a dar mejores diagnósticos y permite el diagnóstico diferencial con patologías más comunes, como la acondroplasia. Se presenta una paciente de 35 años con diagnóstico de síndrome de Grebe desde los 10 años. El síndrome de Grebe tiene una muy baja incidencia; por este motivo, es poco conocido por el cuerpo médico en general y aun menos para los ortopedistas, quienes serán los encargados de tratar a estos pacientes. Nivel de Evidencia: IV

Grebe syndrome is a rare autosomal recessive disorder that belongs to the group of osteochondrodysplasias. Clinically, it is characterized by severe dysmorphism, marked micromelia and deformities of the lower and upper limbs. Recognition of this syndrome allows to give better diagnoses and to establish a differential diagnosis with more common pathologies, such as achondroplasia. We present a 35-year-old woman with diagnosis of Grebe syndrome at the age of 10. Grebe syndrome has a very low incidence; therefore, it is unknown by general physicians and still less by orthopedic surgeons, who will treat these patients. Level of Evidence: IV

Tracheobronchopathia osteochondroplastica / Traqueobroncopatia osteocondroplástica

ABSTRACT Tracheobronchopathia osteochondroplastica is a rare benign disease, of unknown cause, characterized by numerous sessile, cartilaginous, or bony submucosal nodules distributed throughout the anterolateral walls, projecting into the laryngotracheobronchial lumen. In general, tracheobronchopathia osteochondroplastica is diagnosed incidentally during bronchoscopy or autopsy and is not associated with a specific disease. We report the case of a male patient who was diagnosed with tracheobronchopathia osteochondroplastica via bronchoscopy and biopsy.

RESUMO A traqueobroncopatia osteocondroplástica é uma doença benigna rara, de causa desconhecida, caracterizada por numerosos nódulos submucosos sésseis, cartilaginosos e/ou ósseos, distribuídos pelas paredes anterolaterais da traqueia, projetando-se no lúmen laringotraqueobrônquico. Em geral, a traqueobroncopatia osteocondroplástica é descoberta acidentalmente durante broncoscopias ou em necropsias e não é associada a uma doença específica. Relatamos o caso de um paciente que foi diagnosticado com traqueobroncopatia osteocondroplástica por broncoscopia e biópsia.

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.

Congenital adrenal hyperplasia and Schmid metaphyseal chondrodysplasia in a child

Congenital adrenal hyperplasia [CAH] is a group of hereditary diseases, which are autosomal recessive. CAH occurs due to defect in one of the cortisol coding genes and often clinically presents itself with signs of androgen overproduction. In this article, we report a case of CAH and Schmid metaphyseal dysplasia. Our literature review indicated that this report is the first attempt on CYP11B1 and Schmid dysplasia in a child. The specific diagnosis of 11-beta-hydroxylase deficiency can be determined using high basal levels of deoxycorticosterone and/or 11-deoxycortisol serums

Tracheobronchopathia osteochondroplastica: A rare cause of difficult intubation.

Tracheobronchopathia osteochondroplastica is a rare benign airway disorder which is characterised by submucosal nodules projecting into the tracheo-bronchial lumen usually involving the cartilaginous portions of the tracheo-bronchial tree or larynx. The condition is usually asymptomatic but can rarely present with difficulty during endotracheal intubation or rarely with obstructive airway complications. Bronchoscopic appearance is usually sufficient to make the diagnosis, and tissue biopsies are seldom required. No specific treatment is required in asymptomatic patients. However, interventional bronchoscopy procedures or surgery may be helpful in symptomatic cases.

Baja talla por displasia espóndiloepifisaria (DEE) / Stunted by Spondyloepiphyseal dysplasia (DEE)

Clínicamente a los niños que presentan baja talla se los agrupa en dos tipos: los que presentan desproporciones corporales y los que tienen apariencia normal. Entre los primeros se encuentran las displasias esqueléticas, conjunto clínica y genéticamente heterogéneo. La displasia espondiloepifisaria (DEE) es una delas displasias esqueléticas que característicamente presenta acortamiento del tronco y en menor medida de las extremidades; se debe a mutaciones heterocigóticas del gen COL2A1, que codifica el colágeno tipo 2.Se presenta el caso de un niño de 4 años con talla baja y displasia esquelética con características de DEE. La DEE debe diferenciarse de otras displasias óseas. Pueden hallarse estigmas asociados que orienten al diagnóstico a fin de optimizar los exámenes complementarios. El estudio de la mutación, se realiza en los casos en los que se plantean dudas diagnósticas entre varias entidades con rasgos fenotípicos similares...

Summary Clinically children with short stature are grouped in 2: those with alterations in body proportions an those having normal appearance. In the first group are skeletal dysplasias. These terms refer to a clinically and genetically heterogeneous group of disorders of skeletal development and growth. Spondyloepiphyseal dysplasia (SED) is a skeletal dysplasia characteristiccally presenting shortening of the trunk and in a lesser extent, shortening of limbs. It is caused by mutations in COL2A1 gene, encoding the type 2 collagen.A 4 y-o child with short stature and skeletal dysplasia with features of SED is presented. SED must be differentiated from other bone dysplasias. Associated stigmas may guide the likely diagnoses in order to optimize complementary tests. The study of the mutation is performed in cases in which there isdiagnostic doubt among several entities with similar phenotypic traits.

Displasia epifisária hemimélica (doença de Trevor-Fairbank): relato de caso / Dysplasia epiphysealis hemimelica (Trevor-Fairbank disease): case report

Dysplasia epiphysealis hemimelica is a rare benign disease (incidence 1:1,000,000), characterized by an osteochondral overgrowth affecting one or more epiphyses. Generally, the age of onset is between two and 14 years. The characteristic imaging findings are sufficient for the diagnosis. Surgical excision of the lesion is only indicated in cases where a functional limitation is present.

A displasia epifisária hemimélica é uma doença benigna rara (incidência de 1:1.000.000), caracterizada por um crescimento osteocondral decorrente de uma ou mais epífises. Em geral a idade de início é entre 2 e 14 anos. Os achados característicos dos exames de imagem são suficientes para o diagnóstico. A excisão cirúrgica da lesão só é indicada caso haja limitação funcional.

One in three: congenital bent bone disease and intermittent hyperthermia in three siblings with Stuve-Wiedemann syndrome

Stuve-Wiedemann syndrome [STWS] is a rare disorder characterised by congenital bowing of the long bones, contractures of the joints, neonatal onset of respiratory distress, sucking and swallowing difficulties, dysautonomia presenting as episodic hyperthermia, and usually an early death. Three siblings from a consanguineous marriage presented with similar clinical features over 16 years. STWS was established with their last child at the beginning of 2012. All the children exhibited the onset of STWS in the neonatal period with fever and generalised hypotonia. Examinations of all the infants revealed camptodactyly, micrognathia, bent long bones with wide metaphyses, and hypotonia. Only the second affected child had myotonia, demonstrated by electromyography. Unusual pyrexia as a presenting feature in this syndrome needs early recognition so that extensive and elaborate investigations can be avoided. The disorder is usually caused by a mutation in the leukaemia inhibitory factor receptor gene

Traqueobroncopatía osteocondroplástica: presentación simulando asma / Tracheobronchopathia osteochondroplastica. Clinical presentation mimicking asthma

La traqueobroncopatía osteocondroplástica (TO) (o traqueopatía osteocondroplástica otraqueopatía osteoplástica)1 es una entidad rara de etiopatogenia desconocida caracterizada por múltiples nódulos de cartílago o hueso originados en el tejido cartilaginoso de la vía aérea, que se proyectan dentro de la luz traqueobronquial. Generalmente decurso crónico y benigno, es casi siempre un hallazgo; cuando presenta síntomas estos son inespecíficos y se deben al estrechamiento de la vía aérea, al engrosamiento de la pared traqueobronquial, o a alguna complicación. Al ser poco reconocida favorece los errores diagnósticos. Reportamos un caso sintomático de TO, confundida con asma, que además presentaba rinosinusitis crónica e infecciones recurrentes de la vía aérea alta y baja. Además de presentar este caso con gran afectación y progresión hasta bronquios distales, mostramos otros 2 presuntos casos sin confirmación endoscópica.

The tracheobronchopathia osteochondroplastica (TO) is a rare disease of unknown pathogenesis. It is characterized by multiple osteocartilaginous nodules protrudinginto the tracheobronchial airway lumen. Generally it is an incidental finding because its evolution is chronic and benign; when symptoms are present, they are non specific and result from the obstruction of the airway, the thickening of the tracheobronchial wall or some complication. Since it is an uncommon condition the diagnostic errors arefrequent. We report a symptomatic TO case, that was misdiagnosed as asthma, and in addition the patient had chronic sinusitis and recurrent upper and lower respiratory tract infections. This case had progressive invasion of distal bronchi. We also report two other suspected cases without endoscopic confirmation.

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.

A recurrent mutation in Moroccan patients with Dyggve-Melchior-Clausen syndrome: Report of a new case and review.

Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive disorder. It is a spondyloepimetaphyseal dysplasia associated with mental retardation. Clinical manifestations include coarse facies, microcephaly, short trunk dwarfism, and mental retardation. Mutations in Dymeclin gene (DYM), mapped to chromosome 18q21.1, is responsible for DMC. We report here the observation of a consanguineous Moroccan patient having DMC syndrome. The molecular studies showed a previously reported homozygous mutation at c.1878delA of DYM gene. We discuss this recurrent mutation in Moroccan patients with DMC syndrome with a review.

Traqueobroncopatia osteocondroplástica: relato de 2 casos e revisão bibliográfica / Osteochondroplastic tracheobronchopathy: report on 02 cases and bibliographic review

A traqueobroncopatia osteocondroplásica (TO) é uma doença benigna rara, de causa desconhecida, caracterizada por numerosos nódulos submucosos sésseis, cartilaginosos e/ou ósseos, distribuídos pelas paredes ântero-laterais, projetando-se no lúmen laringotraqueobrônquico. Existem aproximadamente 400 casos relatados na literatura mundial. OBJETIVOS: Relatar e discutir 2 casos de TO com a revisão bibliográfica. MATERIAL E MÉTODO: Apresentação de 2 casos, com revisão bibliográfica realizada através dos bancos de dados do MEDLINE, LILACS, PUBMED. DESENHO DO ESTUDO: Estudo observacional, descritivo, relato de casos. CONCLUSÃO: Os sintomas são resultados de obstrução da via aérea, causando tosse seca, dispneia e infecções recorrentes do trato respiratório. A suspeita diagnóstica é feita pela endoscopia de vias aéreas (laringotraqueobroncoscopia), sendo a tomografia computadorizada do tórax/traqueia útil para documentar as características de lesões nodulares. O diagnóstico diferencial inclui a papilomatose, amiloidose e sarcoidose endobronquial, condrossarcoma, hamartoma e linfonodos paratraqueais calcificados. Não existe tratamento específico, porém o prognóstico é bom. A remoção cirúrgica é restrita aos quadros obstrutivos moderados e severos. Os otorrinolaringologistas devem estar atentos e incluírem a traqueobroncopatia osteocondroplástica na lista de diagnósticos diferenciais, quando frente aos sintomas sugestivos de doenças da via aérea superior e árvore traqueobrônquica.

Osteochondroplastic tracheobronchopathy (OT) is a rare benign disorder of the lower part of the trachea and the upper part of the main bronchus characterized by numerous submucosal calcified nodules, sessile, cartilaginous and/or osseous with laryngotracheobronchial lumen projection. There are less than 400 cases reported in the word literature. AIM: to report and discuss 02 cases of OT with a bibliography review. MATERIALS AND METHODS: we report on 02 cases with bibliography revision from MEDLINE, LILACS and PUBMED data. STUDY DESIGN: observational, descriptive, case reports. CONCLUSION: the symptoms result from airway obstruction, causing dry cough, dyspnea and recurrent respiratory tract infections. The diagnostic hypothesis is established by endoscopy of the upper airway (laryngo-tracheo-bronchoscopy), and the trachea/chest computed tomography is the best image exam to define tracheal nodule alterations. The differential diagnoses are papillomatosis, amyloidosis and sarcoidosis chondrosarcoma hamartoma and calcified paratracheal lymph nodes. There is no specific treatment and the prognosis is good. Surgery is restricted to moderate or severe airway obstructions. Otorhinolaryngologists must include OT in the differential diagnosis of cases of upper airway and tracheobronchial tree suggestive symptoms.

Traqueobroncopatía osteocondroplástica: reporte de un caso y revisión de la literatura / Tracheobronchopathy osteochondroplastica: a case report and literature review

La traqueobroncopatía osteocondroplástica es una enfermedad benigna poco frecuente, de etiología incierta, caracterizada por múltiples nodulos submucosos cartilaginosos u óseos en tráquea, bronquios principales y menos frecuentemente, región subglótica y laringe. La presentación clínica de la enfermedad varía desde pacientes asintomáticos, hasta enfermedad severa con obstrucción de la vía aérea. El gold standard para el diagnóstico es la broncoscopía, donde característicamente se visualiza la presencia de múltiples nodulos submucosos que se proyectan hacia el lumen de la vía aérea. La biopsia no es requisito para el diagnóstico. El tratamiento de la enfermedad está dirigido habitualmente al manejo sintomático. En pacientes con severa obstrucción de la vía aérea se han realizado terapias broncoscópicas como ablación con láser, crioterapia o divulsión mecánica de las lesiones. También se ha intentado la resolución quirúrgica, siendo generalmente inefectiva. Presentamos el caso clínico de un paciente evaluado en nuestro servicio, en quien se realizó diagnóstico de traqueobroncopatía osteocondroplástica con compromiso tráqueo-bronquial y subglótico.

Tracheobronchopathy osteochondroplastica is a rare benign disease of uncertain etiology characterized by múltiple cartilaginous or bony submucosal nodules in trachea, bronchi and, less frequently subglottic región and larynx. The clinical presentation of the disease varíes from asymptomatic patients to severe disease with airway obstruction. The gold standard for diagnosis is bronchoscopy, which typically displays the presence of múltiple submucosal nodules that project into the lumen of the airway. Biopsy is not required for diagnosis. The treatment of the disease is usually symptomatic management. In patients with severe airway obstruction bronchoscopic therapies such as laser ablation, cryotherapy or mechanical removal have been performed. Surgical resolution has also been attempted, being generally ineffective. We report the case of a patient evaluated in our department, in whom the diagnosis of tracheobronchopathy osteochondroplastica with tracheobronchial and subglottic compromise was made.

Tracheopathia osteoplastica presenting with haemoptysis in a young male.

A young man presented with infrequent haemoptysis spanning over 10 years. Chest radiograph was normal. However, the computed tomography (CT) of the chest had shown endotracheal wall changes. The diagnosis of tracheopathia osteoplastica was suggested on fiberoptic bronchoscopy and confirmed histologically.