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1.
Pediatr Rev ; 40(8): 435-438, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31371639
2.
BMJ Case Rep ; 12(8)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31413057

RESUMO

Metaphyseal dysplasias are a heterogeneous group of skeletal dysplasias characterised by metaphyseal irregularities. Due to the presence of metaphyseal changes accompanied with bowing deformity of lower limb, they are likely to be mistaken for rickets. We present a case of a 7-year-old boy, finally diagnosed with metaphyseal dysplasia, Spahr type (MDST) (OMIM # 250400) after his exome sequencing revealed novel variations in the MMP13 gene (OMIM * 600108). This is a rare skeletal dysplasia with only a few cases reported in literature. A compilation of the presentation of the reported cases is given to help the reader understand this rare disorder. To the best of our knowledge, this case of MDST is the first to be reported from India.


Assuntos
Osteocondrodisplasias/diagnóstico , Criança , Diagnóstico Diferencial , Humanos , Masculino , Metaloproteinase 13 da Matriz/genética , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , Raquitismo/diagnóstico
5.
Gynecol Endocrinol ; 35(9): 777-781, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30982355

RESUMO

Objective: To investigate the MRI manifestations of congenital vaginal atresia, analyze its imaging features, and improve the understanding of the disease. Methods: MRI findings and clinical data of 12 patients with congenital vaginal atresia confirmed by hysteroscopy and laparoscopic surgery were retrospectively analyzed. Vaginal atresia was classified according to vaginal dysplasia in AFS female genital malformation classification system. Results: In this study, 12 cases of congenital vaginal atresia were diagnosed by combined preoperative MRI with operative diagnosis. Among them, 10 patients all had type-I congenital vaginal atresia, and their uterus and cervix were normal (1 patient had ectopic renal malformation combined with left ovarian endometriosis cyst and 1 patient with uterine empyema). The other two cases were diagnosed congenital vaginal atresia type II (1 case merged with residual uterus, 1 case with cervical dysplasia). MRI mainly manifested as dilatation and hemorrhage in the uterine cavity, cervical canal and vaginal upper segment. T1WI showed high signal, T2WI showed slightly lower and slightly higher signal. The dilated vagina was above the perineal level. Conclusion: MRI features of congenital vaginal atresia have certain characteristics. MRI cannot only accurately assess the type of vaginal dysplasia and its associated complications, but also make objective evaluation and diagnosis, so it can be used as the best effective preoperative image evaluation.


Assuntos
Imagem por Ressonância Magnética , Útero/anormalidades , Útero/diagnóstico por imagem , Doenças Vaginais/congênito , Doenças Vaginais/diagnóstico , Adolescente , Insuficiência Adrenal/diagnóstico , Adulto , Criança , Pré-Escolar , Anormalidades Congênitas/diagnóstico , Diagnóstico Diferencial , Feminino , Retardo do Crescimento Fetal/diagnóstico , Humanos , Lactente , Recém-Nascido , Osteocondrodisplasias/diagnóstico , Estudos Retrospectivos , Anormalidades Urogenitais/diagnóstico , Vagina/anormalidades , Adulto Jovem
6.
J Vet Diagn Invest ; 31(4): 608-610, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31006353

RESUMO

A mature male grizzly bear (Ursus arctos) that died of blunt-force trauma had numerous hard 1-3-mm nodules protruding from tracheal rings into the lumen of the distal trachea. Histologically, these were round aggregates of mature cartilage within the submucosa. Such lesions are consistent with tracheobronchopathia osteochondroplastica, a rare tracheal disease in humans and animals.


Assuntos
Osteocondrodisplasias/veterinária , Doenças da Traqueia/veterinária , Ursidae , Animais , Masculino , Osteocondrodisplasias/diagnóstico , Traqueia/patologia , Doenças da Traqueia/diagnóstico
7.
Zhonghua Bing Li Xue Za Zhi ; 48(4): 303-306, 2019 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-30955267

RESUMO

Objective: To investigate the clinical symptoms, imaging features, pathologic manifestations and diagnosis of tracheobronchopathia osteochondroplastica (TO). Methods: The clinical data, imaging and pathologic features and outcome of 18 TO patients diagnosed at the First Affiliated Hospital of Zhengzhou University from August 2011 to August 2018 were collected and analyzed. Results: The 18 TO patients included 10 males and 8 females; patients' age range was 31 to 64 years (mean 52 years). Six patients (6/18) were smokers. The main presenting clinical symptoms included cough in 15 cases, expectoration in eight cases (8/18), hemoptysis in five cases (5/18), chest tightness in four cases, wheezing in three cases and chest pain in two cases. The time interval between the initial symptoms and diagnosis was 1.5 to 360.0 months, and the average time interval was 45.2 months. Blood calcium and phosphorus were normal in 18 patients (18/18). Chest X-ray showed no direct evidence of TO. Six patients (6/18) showed irregular changes in the trachea or bronchial wall by chest CT scan. Three patients (3/18) had mild ventilatory obstruction. TO was classified as: 10 cases (10/18) were scattered type, seven cases (7/18) were diffuse type and one case (1/18) was confluent type. Epithelial squamous metaplasia, submucosal cartilage, submucosal ossification and hematopoietic bone marrow within the ossified areas were the characteristic histopathologic findings of TO. Conclusions: TO is a rare benign disorder that shows atypical presentation. CT scan is insensitive, the histopathology shows submucosal cartilage or ossification. TO should be diagnosed by comprehensive consideration of clinical symptoms, imaging and pathology.


Assuntos
Osteocondrodisplasias/complicações , Osteocondrodisplasias/diagnóstico , Doenças da Traqueia/complicações , Doenças da Traqueia/diagnóstico , Adulto , Idoso , Brônquios/diagnóstico por imagem , Tosse/etiologia , Feminino , Hemoptise/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
8.
Cytogenet Genome Res ; 157(3): 135-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30933954

RESUMO

We report a patient with developmental delay, brachydactyly type E, short stature, and tetralogy of Fallot. Brachydactyly-mental retardation syndrome (BDMR) was suspected based on the phenotype; however, array CGH excluded a 2q37 deletion, but identified a deletion encompassing the SHOX gene. BDMR is characterized by cognitive impairment, skeletal abnormalities involving hands and feet, short stature, and overweight. Most affected individuals carry relatively large 2q37 deletions encompassing HDAC4. This gene encodes a histone deacetylase involved in epigenetic regulation of cell growth and differentiation, specifically during endochondral bone formation in chondrocyte hypertrophy. Since SHOX haploinsufficiency can cause skeletal defects and short stature but would not fully explain the clinical picture of this patient, exome sequencing was performed, and a heterozygous HDAC8 frameshift mutation was identified. HDAC8 is a distinct histone deacetylase involved in cohesin recycling and is responsible for an X-linked dominant Cornelia de Lange-like phenotype. A new blended clinical phenotype may be explained by the result of a dual molecular diagnosis, which represents a combination of 2 independent genetic defects, with relevant implications for genetic counseling, clinical management, and prognosis.


Assuntos
Síndrome de Lange/diagnóstico , Mutação da Fase de Leitura , Deleção de Genes , Transtornos do Crescimento/diagnóstico , Histona Desacetilases/genética , Osteocondrodisplasias/diagnóstico , Proteínas Repressoras/genética , Proteína de Homoeobox de Baixa Estatura/genética , Criança , Hibridização Genômica Comparativa , Síndrome de Lange/genética , Feminino , Transtornos do Crescimento/genética , Haploinsuficiência , Humanos , Osteocondrodisplasias/genética , Linhagem , Fenótipo , Sequenciamento Completo do Exoma
10.
Arch Pediatr ; 26(2): 102-107, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30638765

RESUMO

BACKGROUND AND OBJECTIVES: Sanjad-Sakati syndrome (SSS; OMIM 241410) is a rare autosomal recessive disorder found almost exclusively in people of Arab origin. It is characterized by congenital hypoparathyroidism, severe prenatal and postnatal growth retardation, and distinct facial dysmorphism. The molecular pathology of this syndrome was shown to be due to a mutation in the tubulin-specific chaperone E (TBCE) gene in chromosomal area 1q42-q43. We aimed to detect and confirm the common mutation responsible for SSS in Tunisian patients and review the literature in order to create a set of clinical diagnostic criteria that might provide appropriate indications for molecular testing. METHODS: Three Tunisian patients with clinical feature of SSS were examined via direct Sanger sequencing of exon 3 of the TBCE gene. RESULTS: Mutation analysis of the TBCE gene revealed the common 12-bp (155-166del) deletion in three new patients, thus raising the number of reported SSS patients to 73. Reviewing the literature, we suggest a scoring system that assigns one point each for major criteria and one half point for minor criteria. INTERPRETATION AND CONCLUSIONS: SSS is an autosomal recessive disorder found in the Middle Eastern population with an estimated incidence of 1 per 40,000-100,000 live births in Saudi Arabia. Reviewing the literature on both its clinical and biochemical characteristics, we suggest for the first time, based on defined major and minor SSS criteria, a clinical scoring system for the diagnosis of SSS. On the one hand, an established scoring system will provide appropriate indications for molecular testing and, on the other hand, reviewed data on SSS will help delineate the phenotype and draw a distinction between differential diagnoses.


Assuntos
Anormalidades Múltiplas/diagnóstico , Transtornos do Crescimento/diagnóstico , Hipoparatireoidismo/diagnóstico , Deficiência Intelectual/diagnóstico , Chaperonas Moleculares/genética , Osteocondrodisplasias/diagnóstico , Convulsões/diagnóstico , Anormalidades Múltiplas/genética , Consenso , Feminino , Marcadores Genéticos , Transtornos do Crescimento/genética , Humanos , Hipoparatireoidismo/genética , Lactente , Recém-Nascido , Deficiência Intelectual/genética , Masculino , Osteocondrodisplasias/genética , Convulsões/genética , Deleção de Sequência , Tunísia
11.
Am J Case Rep ; 20: 74-77, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30655500

RESUMO

BACKGROUND Tracheobronchopathia osteochondroplastica (TO) is a rare idiopathic disease with a stable course, which involves the lumen of the tracheobronchial tree. Clinical manifestations at time of presentation may differ, typically including hoarseness, persistent and/or productive cough, hemoptyses, and dyspnea. There are no well-established guidelines for diagnostic workup and treatment. Our aim here is to present a paradigmatic case of TO together with a concise survey of the most important clinical, radiological, and histological criteria. CASE REPORT We report a case of a 62-year-old non-smoker male with persisting cough and no prior history of respiratory disease. Chest radiography (RX) and computed tomography (CT) were unremarkable. Given the persistence of symptoms, the patient underwent bronchoscopic examination, which revealed protruding sessile nodules into the tracheal lumen, with cobblestone appearance. Histopathological examination of biopsies taken during bronchoscopy showed cartilaginous and osseous submucosal nodules consistent with the diagnosis of TO. CONCLUSIONS TO is not always an easily recognized disease, and a multidisciplinary team work is often required for diagnosis, with particular importance of endoscopic-pathological correlation.


Assuntos
Osteocondrodisplasias/diagnóstico , Doenças da Traqueia/diagnóstico , Broncoscopia , Tosse/etiologia , Humanos , Masculino , Pessoa de Meia-Idade
12.
Front Horm Res ; 51: 147-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641531

RESUMO

Pseudohypoparathyroidism (PHP), pseudo-PHP, acrodysostosis, and progressive osseous heteroplasia are heterogeneous disorders characterized by physical findings, differently associated in each subtype, including short bones, short stature, a stocky build, ectopic ossifications (features associated with Albright's hereditary osteodystrophy), as well as laboratory abnormalities consistent with hormone resistance, such as hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) and thyroid-stimulating hormone levels. All these disorders are caused by impairments in the cAMP-mediated signal transduction pathway and, in particular, in the PTH/PTHrP signaling pathway: the main subtypes of PHP and related disorders are caused by de novo or autosomal dominantly inherited inactivating genetic mutations, and/or epigenetic, sporadic, or genetic-based alterations within or upstream of GNAS, PRKAR1A, PDE4D, and PDE3A. Here we will review the impressive progress that has been made over the past 30 years on the pathophysiology of these diseases and will describe the recently proposed novel nomenclature and classification. The new term "inactivating PTH/PTHrP signaling disorder," iPPSD: (1) defines the common mechanism responsible for all diseases, (2) does not require a confirmed genetic defect, (3) avoids ambiguous terms like "pseudo," and (4) eliminates the clinical or molecular overlap between diseases.


Assuntos
Doenças Ósseas Metabólicas , Disostoses , Deficiência Intelectual , Ossificação Heterotópica , Osteocondrodisplasias , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Hormônio Paratireóideo/metabolismo , Pseudo-Hipoparatireoidismo , Transdução de Sinais/fisiologia , Dermatopatias Genéticas , Doenças Ósseas Metabólicas/classificação , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/terapia , Disostoses/classificação , Disostoses/diagnóstico , Disostoses/metabolismo , Disostoses/terapia , Humanos , Deficiência Intelectual/classificação , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/metabolismo , Deficiência Intelectual/terapia , Ossificação Heterotópica/classificação , Ossificação Heterotópica/diagnóstico , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/terapia , Osteocondrodisplasias/classificação , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/terapia , Pseudo-Hipoparatireoidismo/classificação , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/metabolismo , Pseudo-Hipoparatireoidismo/terapia , Dermatopatias Genéticas/classificação , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/metabolismo , Dermatopatias Genéticas/terapia
13.
J Orthop Res ; 37(1): 171-180, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30273960

RESUMO

DDH is a debilitating condition characterized by incomplete formation of the acetabulum leading to dislocation of the hip, suboptimal joint function and accelerated wear of the articular cartilage resulting in early onset crippling arthritis of the hip in 20-40 year olds. Current diagnostic tests in newborns using physical manipulation of the femur or ultrasound either under or over-diagnose this condition. Developing an accurate, cost effective diagnostic test is a goal of this study. To better understand the biologic pathways involved in acetabular development, DNA from severely affected individuals in a four generation family that showed inter-generational transmission of the disorder was isolated and whole exome sequenced. A novel A to C transversion at position 183721398 on human chromosome four was found to co-segregate with the affected phenotype in this family. This mutation encodes a glutamine to proline change at position 2665 in the Teneurin 3 (TENM3) gene and was judged damaging by four prediction programs. Eight week old knock-in mutant mice show delayed development of the left acetabulum and the left glenoid fossa as shown by the presence of more Alcian blue staining on the socket rims of both the hip and the shoulder. We hypothesize that mutated TENM3 will slow chondrogenesis. MMP13 has been shown to impair extracellular matrix remodeling and suppress differentiation. Bone marrow cells from the knock-in mouse were found to overexpress MMP13 with or without BMP2 stimulation. This variant may elucidate pathways responsible for normal hip development and become part of an accurate test for DDH. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.


Assuntos
Luxação Congênita de Quadril/genética , Artropatias/congênito , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Osteocondrodisplasias/genética , Animais , Condrogênese/genética , Feminino , Luxação Congênita de Quadril/diagnóstico , Humanos , Artropatias/diagnóstico , Artropatias/genética , Masculino , Camundongos , Osteocondrodisplasias/diagnóstico
14.
Eur J Med Genet ; 62(11): 103575, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30439533

RESUMO

Metaphyseal anadysplasia 1 (MIM# 602111) belongs to a heterogeneous group of skeletal diseases characterized by an autosomal dominant form of growth defects due to metaphyseal changes with epiphyseal involvement similar to other metaphyseal disorders. Matrix metalloproteinase 13 encoded by MMP13 presumably plays important roles in bone formation and growth, and pathogenic variants in MMP13 have been identified to cause metaphyseal anadysplasia 1. Only six pathogenic variants in MMP13 have been previously reported worldwide. The genotype-phenotype correlation of MMP13-related disorders has not been fully understood. Here we reported the identification of a previously unreported pathogenic heterozygous de novo variant NM_002427.3:c.212T > C/p.Met71Thr in MMP13 in a Chinese male pediatric patient with metaphyseal anadysplasia 1 and additional phenotypes, including mild rickets-like changes observed on upper long bone metaphyses and patchy bone defects on the spine vertebrae particularly resolved by childhood. Our findings not only expand genotype and phenotype spectrums of MMP13-related disorders but also offer further information for precise diagnosis and classification of metaphyseal anadysplasia disorders.


Assuntos
Desenvolvimento Ósseo/genética , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/genética , Metaloproteinase 13 da Matriz/genética , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Criança , Genótipo , Heterozigoto , Humanos , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/fisiopatologia , Masculino , Mutação/genética , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/fisiopatologia , Osteogênese/genética , Linhagem , Fenótipo
15.
Front Neuroendocrinol ; 52: 113-143, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30448536

RESUMO

Individuals with acromegaloid physical appearance or tall stature may be referred to endocrinologists to exclude growth hormone (GH) excess. While some of these subjects could be healthy individuals with normal variants of growth or physical traits, others will have acromegaly or pituitary gigantism, which are, in general, straightforward diagnoses upon assessment of the GH/IGF-1 axis. However, some patients with physical features resembling acromegaly - usually affecting the face and extremities -, or gigantism - accelerated growth/tall stature - will have no abnormalities in the GH axis. This scenario is termed pseudoacromegaly, and its correct diagnosis can be challenging due to the rarity and variability of these conditions, as well as due to significant overlap in their characteristics. In this review we aim to provide a comprehensive overview of pseudoacromegaly conditions, highlighting their similarities and differences with acromegaly and pituitary gigantism, to aid physicians with the diagnosis of patients with pseudoacromegaly.


Assuntos
Acromegalia/diagnóstico , Transtornos Cromossômicos/diagnóstico , Diagnóstico Diferencial , Gigantismo/diagnóstico , Transtornos do Metabolismo de Glucose/diagnóstico , Hipotireoidismo/diagnóstico , Lipodistrofia/diagnóstico , Síndrome de Marfan/diagnóstico , Anormalidades Musculoesqueléticas/diagnóstico , Osteocondrodisplasias/diagnóstico , Acromegalia/metabolismo , Transtornos Cromossômicos/metabolismo , Gigantismo/metabolismo , Transtornos do Metabolismo de Glucose/metabolismo , Humanos , Lipodistrofia/metabolismo , Anormalidades Musculoesqueléticas/metabolismo
16.
Am J Med Genet A ; 179(1): 123-129, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561107

RESUMO

Terminal osseous dysplasia with pigmentary defects (TODPD; MIM #300244) is an extremely rare, X-linked dominant, in utero male-lethal disease, characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibromatosis of childhood. Delayed/abnormal ossification of bones of the hands and feet, joint contractures, and dysmorphic facial features may accompany. A single recurrent mutation (c.5217 G>A) of the FLNA gene which causes cryptic splicing was identified as the cause of the disease. We here present the first TODPD case from Turkey with full-blown phenotype who exhibit unique additional findings, hypopigmented patch on the lower extremity following Blaschko's lines and smooth muscle hamartoma of the scalp in review of all the previously reported TODPD cases.


Assuntos
Doenças do Desenvolvimento Ósseo/fisiopatologia , Filaminas/genética , Dedos/anormalidades , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Deformidades Congênitas dos Membros/fisiopatologia , Osteocondrodisplasias/fisiopatologia , Transtornos da Pigmentação/fisiopatologia , Pele/fisiopatologia , Dedos do Pé/anormalidades , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/genética , Pré-Escolar , Feminino , Dedos/diagnóstico por imagem , Dedos/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico por imagem , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mãos/fisiopatologia , Humanos , Hipopigmentação/diagnóstico por imagem , Hipopigmentação/genética , Hipopigmentação/fisiopatologia , Lactente , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/genética , Mutação , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , Fenótipo , Transtornos da Pigmentação/diagnóstico , Transtornos da Pigmentação/diagnóstico por imagem , Transtornos da Pigmentação/genética , Dedos do Pé/diagnóstico por imagem , Dedos do Pé/fisiopatologia , Turquia/epidemiologia
18.
Med Arch ; 72(4): 289-291, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30514997

RESUMO

Introduction: Wolcott-Rallison syndrome (WRS) is a rare, autosomal recessive disorder with infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, osteopenia, mental retardation or developmental delay, and hepatic and renal dysfunction as main clinical findings. Cardiovascular system is very rarely affected and there are a limited number of publications where WRS is associated with congenital heart disease. The aim of this interesting case is to report an infant with Wolcott - Rallison syndrome, type I diabetes mellitus, and complex congenital heart disease, diagnosed in a pre term neonate. Case report: A case of preterm neonate who presented immediately after delivery with hyperglycemia and heart murmur. Clinical and laboratory investigation showed diabetes mellitus type I and double outlet right ventricle. Genetic examination showed classic mutations in the EIF2AK3 gene - eukaryotic translation initiation factor 2α kinase 3. Conclusion: Diabetes in neonatal age raises doubts about the possibility of association with the syndrome and other diseases.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/terapia , Epífises/anormalidades , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/terapia , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/terapia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro
19.
BMC Med Genet ; 19(1): 212, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541462

RESUMO

BACKGROUND: Dwarfism is a common severe growth disorder, but the etiology is unclear in the majority of cases. Recombinant human growth hormone may be a treatment option, but it has limited efficacy. The currently known laboratory assays do not meet the precision requirements for clinical diagnosis. Here, we have constructed a targeted next-generation sequencing (NGS) panel of selected genes that are suspected to be associated with dwarfism for genetic screening. METHODS: Genetic screening of 91 children with short stature of unknown etiology was performed with the help of the NGS panel. All the coding regions and exon-intron boundaries of 166 genes were included in the panel. To clarify the pathogenicity of these mutations, their clinical data were reviewed and analyzed. RESULTS: The assay identified p.A72G, p.I282V, and p.P491S variants of the PTPN11 gene and a p.I437T variant of the SOS1 gene in 4 cases with Noonan syndrome. A frameshift mutation (p.D2407fs) of the ACAN gene was identified in a case of idiopathic short stature with moderately advanced bone age. A p.R904C variant of the COL2A1 gene was found in a patient, who was accordingly diagnosed with Stickler syndrome. Severe short stature without limb deformity was associated with a p.G11A variant of HOXD13. In addition, we evaluated evidence that a p.D401N variant of the COMP gene may cause multiple epiphyseal dysplasia. CONCLUSIONS: Our findings suggest that syndromes, particularly Noonan syndrome, may be overlooked due to atypical clinical features. This gene panel has been verified to be effective for the rapid screening of genetic etiologies associated with short stature and for guiding precision medicine-based clinical management.


Assuntos
Artrite/genética , Doenças do Tecido Conjuntivo/genética , Nanismo/genética , Perda Auditiva Neurossensorial/genética , Mutação , Síndrome de Noonan/genética , Osteocondrodisplasias/genética , Descolamento Retiniano/genética , Adolescente , Agrecanas/genética , Artrite/diagnóstico , Artrite/etnologia , Artrite/patologia , Grupo com Ancestrais do Continente Asiático , Proteína de Matriz Oligomérica de Cartilagem/genética , Criança , Pré-Escolar , Colágeno Tipo II/genética , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/etnologia , Doenças do Tecido Conjuntivo/patologia , Nanismo/diagnóstico , Nanismo/etnologia , Nanismo/patologia , Feminino , Expressão Gênica , Testes Genéticos/métodos , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etnologia , Perda Auditiva Neurossensorial/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/genética , Humanos , Masculino , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/etnologia , Síndrome de Noonan/patologia , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/etnologia , Osteocondrodisplasias/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etnologia , Descolamento Retiniano/patologia , Proteína SOS1/genética , Fatores de Transcrição/genética
20.
Medicine (Baltimore) ; 97(50): e13644, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558059

RESUMO

RATIONALE: Spondyloenchondrodysplasia (SPENCD) is an autosomal recessive skeletal dysplasia by biallelic mutations in ACP5 gene encoding tartrate-resistant acid phosphatase (TRAP). The extra-osseous phenotype of SPENCD is pleiotropic and involves neurological impairment and immune dysfunction. Dentofacial abnormalities and orofacial symptoms in SPENCD patients have been little discussed in the literature. PATIENTS CONCERNS: Herein we present clinical and radiological data regarding 2 siblings with SPENCD. Both patients exhibited short stature, cervical platyspondyly, growth disturbance with multiple skeletal deformities of the wrist, and systemic lupus erythematosus related autoimmunity. They experienced prolonged pain in the temporomandibular joint (TMJ) area and exhibited delayed dental development. One patient presented with midface hypoplasia, retrognathic mandible, and anterior openbite. Computed tomographic images demonstrated delayed spheno-occipital synchondrosis, obtuse cranial base angle, overdeveloped and anteriorly displaced sphenoidal sinuses, and compressed ethmoidal sinuses. DIAGNOSIS: The genetic analysis revealed heterozygous for a missense mutations at ACP5 in both probands. INTERVENTIONS: Routine follow-up with conservative treatment were conducted for 12 months. OUTCOMES: The elder sister's orofacial pain was relieved but the boy showed sustained masticatory and cervical muscle pain and TMJ arthralgia which had changed in accordance with systemic condition. No further teeth eruption or skeletal growth was observed in 2 siblings during the follow-up period. LESSONS: These findings extend the phenotypic spectrum of SPENCD and indicate that compromised endochondral ossification and the loss of TRAP activity may affect altered dentofacial development and orofacial symptoms.


Assuntos
Doenças Autoimunes , Tratamento Conservador/métodos , Anormalidades Craniofaciais , Lúpus Eritematoso Sistêmico , Osteocondrodisplasias , Fosfatase Ácida Resistente a Tartarato/genética , Articulação Temporomandibular , Adolescente , Assistência ao Convalescente , Artralgia/diagnóstico , Artralgia/etiologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/imunologia , Anormalidades Craniofaciais/fisiopatologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etiologia , Masculino , Mutação de Sentido Incorreto , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Osteocondrodisplasias/imunologia , Osteocondrodisplasias/fisiopatologia , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Erupção Dentária
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