Chromosome deletion and multiple cartilaginous exostoses

We report a 13 year-old girl with manifestations strikingly reminiscent of the tricho-rhino-phalangeal (TRP) II or Langer-Giedion syndrome. A terminal deletion of 8q must be assumed to be the cause of her condition till proven otherwise. A similar chromosome abnormality should be searched for (blindly) in other cases of the TRP II previously thought to have had normal chromosomes.Dedicated to Prof. Dr. H.-R. Wiedemann on the occasion of his 65th birthday     

Radiographic findings in hereditary multiple exostoses and a new theory of the pathogenesis of exostoses

Analysis of 330 exostoses in 18 patients affected by hereditary multiple exostoses disease suggested a new classification of exostoses as eccentric or full-thickness. Radiographically arrest of metaphyseal remodeling with failure of coning and persistence of the primary metaphyseal trabeculae was evident in full-thickness exostoses. Similar bone lesions can be obtained experimentally with inhibitors of bone turn-over. A localized, peripheral defect in remodeling over a limited time can give a satisfactory explanation also for the origin of eccentric exostoses. The thesis that this is the basic mechanism of exostosis formation is presented.     

Fetal alcohol syndrome and bilateral tibial exostoses

Maternal exposure to alcohol during pregnancy has been associated with fetal malformations referred to as the fetal alcohol syndrome. This paper describes, for the first time, the presence of bilateral tibial exostoses in a child with FAS.     

Hereditary multiple exostoses and acute myeloid leukemia: an unusual association

Hereditary multiple exostoses (HME) is an autosomal dominant disorder characterized by the presence of multiple exostoses. Threegenetic loci have been identified, of which two (EXT1 and EXT2) have tumor suppressor activity. HME greatly increases the risk to develop sarcoma in the dysplastic tissue. The authors report an 8-year-old girl with HME who developed acute myeloblastic leukemia.     

多器官功能障碍综合征和多器官衰竭

多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)是指机体遭受严重创伤、休克、感染及外科大手术等急性损害24h后,同时或序贯性出现2个或2个以上的系统或器官功能障碍或衰竭,即多个器官功能改变不能维持内环境稳定的临床综合征;多器官衰竭(multiple organ failure,MOF)是MODS继续进展的最严重的终末期阶段。     

遗传性多发性外生骨疣一家系3代5例报告

多发性外生骨疣也称为干骺部连续症,以强调干骺部漏斗状塑造的畸形或称骨软骨瘤病。是一种常染色体显性遗传性骨病。有蒂骨性肿物常见于长骨干骺端,出生时即可发生,并且在大小和数目上可不断增长,直到骨骺闭合为止。现将一家系3代5例报道如下。     

尺骨远端遗传性多发性骨软骨瘤病的特点与治疗

目的探讨尺骨远端遗传性多发性骨软骨瘤病的病变特点和治疗效果。方法回顾性地分析了14例23侧累及尺骨远端的多发性骨软骨瘤病例,有2侧采用非手术治疗,5侧接受了瘤体切除手术,17侧接受了尺骨延长术,5侧接受了桡骨截骨术。比较了手术前后的前臂功能和外观变化。并对桡骨头脱位和尺骨弯曲的相关性进行了统计学分析。结果本组病例术后前臂短缩、弯曲和时关节畸形改善较为明显。部分病例切除部分瘤体后,使尺骨远端的部分骺板开放。在尺骨延长后,部分病例桡骨远端的尺偏角也显著减少。但肘、腕关节主动屈、伸活动度、前臂旋前、旋后活动度、以及握力在术前和术后的测量值差异均无显著性意义。手术也不能使脱位的桡骨头良好复位。在桡骨头脱位的病例中,尺骨弯曲度为24．2°±7．5°,在没有桡骨头脱位的病例中,尺骨的弯曲度为6．5°±5．1°,两者差异有非常显著性意义。结论桡骨头脱位和尺骨弯曲有密切的相关性,手术治疗对外观改善较为明显,但无助于患肢功能改善,应依据病变的具体情况制定个性化的手术方案,如果决定采用手术治疗,早期手术疗效更好。     

Diagnosis of hypochondroplasia: the role of radiological interpretation

Background. Hypochondroplasia is characterised by phenotypic and genetic heterogeneity. Differentiation from other conditions with disproportionate short stature is often difficult. Objective. To determine the reliability of radiological interpretation in the diagnosis of hypochondroplasia and to evaluate the most typical skeletal abnormalities. These data were correlated with molecular findings. Materials and methods. We enrolled 21 patients with suspected hypochondroplasia based on the radiological criteria most often reported in the literature on this disease. Height, sitting height and head circumference were measured in all patients. Radiographs of the lumbar spine, left leg, pelvis and left hand were obtained. The presence of the N540K mutation in the fibroblast growth factor receptor 3 (FGFR3) gene was verified by restriction enzyme digestion. All radiographs which enabled the selection of patients were reviewed a second time by two paediatric radiologists in a blinded examination. Their results were compared. Results. Both radiologists confirmed the diagnosis in 10 out of 21 patients, while in the other 52 % of cases they excluded the disease, were uncertain or they did not agree on the final interpretation of the data. The best agreement rate was obtained in the evaluation of the lumbar spine and the legs. The radiological features of the nine patients (43 %) carrying the N540K substitution were not remarkably different from the ones reported in the patients without this mutation. Conclusion. Our study shows that the crucial skeletal regions on which to focus the diagnosis of hypochondroplasia are the lumbar spine and legs, while the pelvis and hands seem to be less characteristic. To reduce the risk of misdiagnosis, accurate radiological and clinical evaluation is needed, especially in cases without a defined genetic defect. Received: 15 November 1999 Accepted: 8 May 2000     

遗传性多发性骨软骨瘤基因突变检测:附一家系报告

目的 对1例遗传性多发性骨软骨瘤(HME)家系的EXT1和EXT2基因编码序列进行突变检测,寻找引起该家系HME的致病基因突变.方法 PCR扩增先证者EXT1和EXT2的各外显子及其侧翼序列,PCR产物经割胶纯化后,直接测序分析.结果 DNA测序分析发现,先证者EXT1基因第1外显子有一新的杂合缺失-插入突变(651-664delinsTTT),致使EXT1基因编码蛋白218位后的氨基酸发生移码突变,在220位处提前出现终止密码(K218fsx220),使编码的EXT1,蛋白为截断型蛋白.家系调查发现,该突变来自于先证者母亲.先证者EXT2基因没有发现变异.结论 EXT1基因651-664delinsTTT杂合突变,是引起该家系HME的分子机制.     

Multiple pterygium syndrome: mimicking the findings of Turner syndrome

Multiple pterygium syndrome (MPS or Escobar syndrome) is a rare, generally autosomal recessive disorder characterized by multiple congenital joint contractures and multiple skin webs. An 11.5-year-old girl with a working diagnosis of Turner syndrome (TS) was referred for her phenotypic features and growth retardation. Pterygium of the neck, low posterior hairline, widely spaced nipples, cubitus valgus, upslanting palpebral fissures, hypertelorism, micrognathia, low-set ears, downturning corners of the mouth, long philtrum, high-arched palate, digital and intercrural webbings, and aplasia of the labia majora were indicative of MPS (Escobar syndrome). Her mental status was normal. Facial asymmetry was present due to cervical webs. Normal karyotype, gonadal functions, and cardiac and urinary system findings helped in excluding TS. Genetic diseases associated with skin webs were revised in differential diagnosis.     

1例遗传性多发性骨软骨瘤家系EXT1基因分析

目的 遗传性多发性骨软骨瘤（HME）是一种常染色体单基因显性遗传骨发育异常疾病,超过70% 为EXT1、EXT2 突变所致。该文目的是分析一HME 家系（3 代24 名成员,6 名HME 患者）临床特征及致病基因与突变;并通过文献复习统计分析中国人种基因突变情况。方法 收集、整理、分析该家系临床资料;应用PCR 及直接测序进行EXT1 基因分析;应用Pubmed 及万方数据库检索中国人种HME 基因突变文献。结果 （1）该家系起病年龄逐代变早,骨软骨瘤发作部位及数量逐代增多,身体变形逐代严重。（2）患者均发现EXT1 基因杂合剪切突变IVS5+1G>A,该突变在中国人中首次发现。（3）至今中国HME 家庭（含该家系）基因突变构成比为EXT1 为29%（26/90）,EXT2 为43%（39/90）。结论 （1）该HME 家系呈现病情逐代加重情况。（2）该家系由EXT1 基因剪切突变IVS5+1G>A 导致发病。（3）中国人种EXT1、EXT2 突变构成比与西方人不一致。     

Spontaneous regression of exostoses: Two case reports

Exostoses are a common skeletal disorder. Despite their incidence, little is yet known about their origin and biological behaviour. In particular, spontaneous regression of exostoses — an extremely rare event — is still a subject for debate. In this study, we describe two additional cases of spontaneous regression of exostosis; one was a solitary lesion while the other occurred in a patient with multiple heritable exostoses. Radiographic findings are presented along with some of the theories which aim at explaining this phenomenon.     

软骨发育不全与软骨发育低下家系的FGFR3基因突变分析

目的了解临床诊断为软骨发育异常类疾病患儿及其家系成员的成纤维细胞生长因子受体3(FGFR3)基因突变情况。方法应用聚合酶链式反应(PCR)和DNA测序技术分析7例患儿及其家系成员的FGFR3基因突变热点分布区域第10外显子以及第13外显子的序列。结果 4例患儿存在FGFR3基因第10外显子c.1138GA(p.Gly380Arg)杂合突变,确诊为软骨发育不全(ACH),其父母未见突变。1例症状较轻微的患儿及其有同样表型的母亲存在FGFR3基因第13外显子c.1620CA(p.Asn540Lys)杂合突变,确诊为软骨发育低下(HCH)。2例患儿未发现以上两个位点的突变。结论检测FGFR3基因第10、第13外显子可诊断大部分ACH或HCH病例,但少数患儿尚有必要检测FGFR3基因其他区域及其他相关基因以明确诊断。     

捂热综合征合并多脏器功能损伤及血浆渗透压改变28例初探

目的对28例捂热综合征患儿血生化，血浆渗透压，肺、心、脑、肾脏的变化进行系统观察，旨在探讨捂热后机体内环境的改变及重要脏器损害情况。方法收集新密市中医院1998-2005年较为完整的捂热综合征病例28例，早、中、晚期测定血生化、血浆渗透压、拍X线胸片、心电图、肝功能、肾功能及头颅CT检查及临床系统观察。结果人院后给予积极治疗，结果存活24例，随访1年后16例无异于正常同龄儿，8例有轻重不同的智力滞后。死亡3例，放弃治疗1例。结论捂热综合征治疗的关键在于早发现、早就诊、早治疗，及早改善缺氧状态。积极纠正脱水、电解质紊乱及酸碱失衡，尽早保护心、肺、脑、肾等重要器官，避免引起多脏器功能衰竭。     

Multiple sulphatase deficiency and haemophagocytic syndrome

A 3-year-old boy with multiple sulphatase deficiency, complicated by a haemophagocytic syndrome, recovered with conventional treatment. Haemophagocytic syndrome can be a complication of many disorders including metabolic diseases, frequently triggered by intracellular viral and bacterial infections or even by drug administration. Received: 8 October 1996 / Accepted in revised form: 5 September 1997