软骨发育不全一家系13例

先证者 ( 1 1 )　男 ,36岁 ,未婚 ,身高 135 cm,智力正常 ,头颅增大 ,前额突出 ,马鞍形鼻梁 ,嘴唇肥厚向外突。胸椎后突 ,腰椎前突 ,臀部肥大 ,胸腔扁小 ,肋骨较常人短 ,手指粗短 ,下肢呈弓形 ,走路摇摆 ,象鸭步 ,四肢肌力正常 ,能胜任日常工作。家系调查 (图 1)　本家系 4代 4 8人 ,患者 13人 (男 9人、女 4人 ) , 3病情较重 ,走路摇摆明显 ,常摔倒 ,生活能自理 ,已死亡。图 1　软骨发育不全家系图　　讨论　软骨发育不全是一种最为常见的侏儒畸形之一 ,呈常染色体显性遗传 ,其发生频率约为 1/ 2 6 0 0。检出率可高达99%。其基本病理变化是…     

FGFR3基因突变分析鉴别软骨发育不全及类似遗传性侏儒

目的 了解中国人软骨发育不全患者（ａｃｈｏｎｄｒｏｐｌａｓｉａ,ＡＣＨ）的基因突变情况,建立一种快速简便的从分子水平鉴别ＡＣＨ及类似遗传性侏儒的方法。方法 对２１例ＡＣＨ患者及６例颖似ＡＣＨ患者的干血滤纸片进行成纤维细胞成长因子受体３（ｆｉｂｒｏｂｌａｓｔ ｇｒｏｗｔｈ ｆａｃｔｏｒ ｒｅｃｅｐｔｏｒ３,ＦＧＦＲ３）基因跨膜区特异性扩增,通过限性内切酶分析、单链构象多态和变性梯度凝胶电泳检测基因突     

软骨发育不全二例报告及文献复习

目的研究软骨发育不全的临床、影像学和病理学表现。方法复习1447例尸检中诊断为软骨发育不全的2例作回顾性研究。结果软骨发育不全患者身体长度基本正常而肢体较短,短肢以臂、大腿肢体近端为主。头颅增大,鼻梁塌陷,腰椎前凹,胸腔扁而小,肋骨异常的短。手指粗而短分开似＂三叉戟＂,肘生长受限。结论软骨发育不全是侏儒最常见的原因,在病理学上具有明显的特征性改变。     

陕西关中地区软骨发育不全10例报告

本文对软骨发育不全１０例确诊患者的临床表现及骨Ｘ线所见作了详细分析。结果表明每例均有侏儒及身体比例的失调。骨Ｘ线均有四肢骨粗短弯曲,干骺端宽,骨皮质增厚,指趾短状骨粗短,２／３病例有额骨隆起,颅底短,方形髂骨翼,腰椎椎弓根间距变窄,坐骨大切迹变短且狭小等特点。     

软骨发育不全1例基因突变检测

目的对1例临床诊断为软骨发育不全（achondroplasia,ACH）的患者及其父母的成纤维细胞生长因子受体3（fibroblastgrowthfactorreceptor3,FGFR3）进行基因突变检测。方法提取患者及其父母外周血DNA,对FGFR3基因的第10外显子区设计引物,进行PCR扩增,并对扩增产物进行限制性内切酶酶切分析。结果与父母及正常对照相比,此例患儿FGFR3基因第10外显子发生了第1138位G到A的点突变。结论FGFR3基因第10外显子G1138A杂合突变可能为该例软骨发育不全患者的主要病因。该检测结果与国内外研究结果一致,进一步说明该突变为热点突变。     

胎儿软骨发育不全的超声诊断

目的 探讨超声诊断胎儿软骨发育不全的声像图特征和临床意义.方法 从近4万名孕期超声检查的孕妇中检出胎儿软骨发育不全4例.结果 胎儿四肢长骨粗短,胸廓呈古钟状,头颅增大,腹部膨隆是胎儿软骨发育不全的主要声像图表现.结论 超声诊断是初步筛查软骨发育不全的理想方法.     

软骨发育不全(肢中部侏儒)1例报道

病例:患儿刘某,男,5岁,足月顺产,G1P1产后发现四肢短小,尤其是前臂及小腿.伴有腓骨及尺骨严重发育不全,下颌小,1.2岁时会走路.查体:头颅发育正常,身材矮小,四肢管状骨过短而弯曲,与头围躯干不成比例,手指呈车轮样展开,指短,"X"型腿,走路呈摇摆状,生活自理性差,智力发育正常.     

软骨发育不全一例

患儿女，3岁，因生长发育落后3年入院。患儿系G1P1，出生体重及身高不详。生后其父母发现患儿生长发育落后于同龄儿，头发稀疏，前囟闭合延迟，身材矮小。运动发育落后，2岁左右才能独走，语言、智力发育正常。父亲身高正常，母亲为侏儒（身高110cm，原因不明），其母的一兄一弟体格发育正常。查体：体重10kg，身高73cm，头围50cm，上部量大于下部量。头大，四肢短，直立时双手下垂指尖仅能触及腹股沟，前额宽而突出，前囟未闭（1cm×1cm）。轻度摇摆步态，腰部前突，臀部后突，O型腿。辅助检查：四肢长骨正侧位X摄片：四肢粗短，双侧肱骨短，远端膨大，双侧尺桡骨远端变尖；双侧股骨下端外份骨密度低，双侧股骨下端及双侧胫骨上、下端膨大。腕关节正位片：左侧腕关节见两枚腕骨发育。肝肾功检查正常，血钙2．51mmol／L，磷1．75mmol／L，碱性磷酸酶正常，生长激素、甲状腺激素均正常，头颅CT未见明显异常。诊断为软骨发育不全。     

一例COMP基因杂合突变致假性软骨发育不全病例

目的 对假性软骨发育不全（PSACH）确诊患儿及其家系成员进行软骨寡聚基质蛋白（COMP）基因检测,并进行分析。方法 采集患儿及父母清晨空腹外周静脉血各5 mL,抽取基因组DNA,进行PCR扩增,采用高通量测序方式读出原始测序数据;同时,对于致病突变基因所在片段上下游设计引物,进行PCR扩增,对产物行Sanger测序。结果 患儿存在杂合突变c.1048＿1116del(exon 10,NM＿000095),导致氨基酸发生整码突变（p.N350＿D372del）。患儿父母均未检测出COMP基因突变位点。结论 COMP基因第10外显子杂合突变c.1048＿1116del(exon 10,NM＿000095)为PSACH的致病突变,在国内外PSACH患者中属于首次发现。患儿父母外周血基因正常,提示其父母可能与该突变的生殖腺嵌合体有关。     

软骨发育不全的产前基因诊断

目的 通过产前成纤维细胞生长因子受体3(fibroblast growth factor receptor 3,FGFR3)基因检测确诊胎儿软骨发育不全.方法 经脐带穿刺获取78例短肢发育异常胎儿脐血,常规行核型分析,并提取基因组DNA,扩增FGFR3基因第10外显子,应用限制酶Bfm I进行限制性片段长度多态性分析,并对其行DNA双向测序.同法分析阳性胎儿双亲FGFR3基因第10外显子.结果 短肢发育异常78例胎儿中,8例为G1138A杂合突变,诊断为软骨发育不全,其核型分析正常.余70例短肢发育异常胎儿,FGFR3基因第10外显子第1138位核苷酸检测结果正常,排除软骨发育不全.8例患病胎儿双亲中,1例父亲同为G1138A杂合突变,余检测结果正常.结论 对超声诊断的胎儿短肢发育异常,通过脐血FGFR3基因第10外显子的PCR-限制性片段长度多态分析和DNA双向测序,产前能明确诊断软骨发育不全.     

Weight gain velocity in infants with achondroplasia

There are virtually no data regarding appropriate oral intake in infants with dwarfing disorders such as achondroplasia, nor is there clear information regarding appropriate weight gain velocity in this population. Yet, these individuals are at increased risk for both early failure to thrive and, later in life, for obesity. Having appropriate expectations regarding weight gain and reasonable goals in management is imperative. We sought to clarify the rate of weight gain in infants with achondroplasia during the first year of life through analysis of data from 60 infants with achondroplasia seen at least twice during the first year of life in the Midwest Regional Bone Dysplasia Clinic, University of Wisconsin‐Madison between 1998 and 2018. The mean weight gain velocity during the first 3 months was 23 g/day which contrasts with 30 g/day in average statured infants. Mean weight gain from 0 to 12 months of age was 13 g/day. The 3% of weight gain velocity during the first year of life was 8 g/day, and this rate did not differ between 0–3 months and 0–12 months of age. Infants with achondroplasia slightly more than doubled their birth weights by 1 year of age in contrast to averaged statured infants who typically triple birth weights by 1 year. Infants with achondroplasia can be thriving but erroneously assessed as failing to thrive if the incorrect reference values are used. This article describes infant weight gain velocity reference data for this population.     

Bes, Aesop and Morgante: reflections of achondroplasia

The past perception of achondroplasia is reflected in art, beginning about 2000 B.C. Achondroplasia is thought to have provided a model for the representation of a series of figures including the Egyptian god Bes, the Greek teller of fables Aesop, and the Renaissance giant of fiction Morgante. Since these figures were basically viewed as good, the hypothesis is advanced that achondroplasia was perceived as a positive, not a negative, condition during at least part of the past four millenia.     

危重型手足口病3例尸检临床病理分析

目的 探讨危重型手足口病死亡患者各脏器的病理改变特点,并分析其死亡原因.方法 对3例危重型手足口病死亡病例作尸体解剖,镜检各脏器的病理改变,并分析主要脏器的病理改变与临床症状和体征的关系,探讨导致患者死亡的病变基础.结果 危重型手足口病起病急,进展快,病程短,临床表现为发热、手足口疱疹、神经系统症状和突发性呼吸窘迫.病变累及的关键脏器是延髓、脑干和肺脏.延髓和脑干的病理改变是神经元变性坏死、脑软化灶形成、出现血管周围炎细胞浸润和噬神经细胞现象,呈病毒性脑炎改变.肺的病理改变是肺泡间隔毛细血管扩张充血,并大量单核细胞浸润;肺泡腔内大量单核细胞渗出,填满肺泡腔,致局部肺实变;局部肺透明膜形成;局部肺组织出血性梗死;局部肺泡腔内有大量水肿液;呈严重病毒性肺炎和急性肺水肿改变.此外,淋巴结和脾脏的结构破坏,淋巴小结萎缩,淋巴滤泡的生发中心细胞核碎裂,呈生发中心烧毁现象.结论 危重型手足口病病毒侵犯患者肺、延髓、脑干和免疫器官,导致病毒性肺炎、病毒性脑炎和免疫器官损害.其中,延髓和脑干呼吸中枢的损害与肺部本身的严重病变协同作用引起的呼吸衰竭,是病人死亡的主要原因.     

Growth and growth hormone therapy in children with achondroplasia: A two-year experience

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8–12.2 years of age) and 12 girls (5.7–2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week. Auxological assessments were performed 6 months before, at initiation of, and at 6, 12, and 24 months following initiation of growth hormone (GH) therapy. Before initiating GH therapy, hypothalamic-pituitary and thyroid functions were evaluated. Levels of serum insulin-like growth factor (IGF)-I and IGF binding protein (BP)-3 (IGFBP-3) were assessed, as was GH response to provocative stimuli. GH responses in two stimulation tests were normal for all but three children. During the first semester of GH treatment, a significant increase in height velocity (HV), from 3.2 to 8.3 cm/year, was observed in all children. However, during the second semester, a relative decrease in growth rate was observed. By the end of the first year, HV had increased from 3.2 to 6.9 cm/year (mean, 3.7 cm/year; range, 1.1–8 cm/year) in 13 children and remained unchanged in two children. HV declined progressively during the next 12 months and, by the end of the second year of treatment, had increased in seven of the nine children who had completed 2 years of therapy (mean increase, 3.1 cm/year); two children did not respond to GH therapy, as shown by the lack of increase in HV. Sitting-height (SH) to standing-height ratio % (SH%) remained unchanged throughout GH therapy, and no significant change in skeletal maturation was observed. In conclusion, hGH treatment resulted in an increased growth rate in some children with achondroplasia; however, this increase waned during the second year of treatment. Children with the lowest pretreatment HVs seemed to benefit most from GH therapy. Nonetheless, the usefulness of GH treatment in achondroplasia will be known only when a study of final height is completed. Am. J. Med. Genet. 72:71–76, 1997. © 1997 Wiley-Liss, Inc.     

Recurrence risk for sibs of children with “sporadic” achondroplasia

Because of gonadal mosaicism, the risk of recurrence of achondroplasia in the sibs of achondroplastic children with unaffected parents is presumably higher than twice the mutation rate, but it has not been measured. Data from 11 Canadian genetics centers provide an estimate of 1/443, or 0.02%. Am. J. Med. Genet. 90:250–251, 2000. © 2000 Wiley‐Liss, Inc.     

Functional health status of adults with achondroplasia

Little is known regarding the functional health status of individuals with achondroplasia. This cross-sectional survey of adults with achondroplasia was undertaken to assess the functional health status of this population and its determinants. The study sample consisted of members of the Little People of America (LPA) who completed a mailed questionnaire consisting of a demographics component, a general and disease-specific comorbidities component, and the Short Form 36 (SF-36) health status questionnaire. Univariate analyses and multivariate linear regression models were used for data analysis. Four hundred thirty-seven individuals with a mean age of 38 years completed the survey. The age- and gender-adjusted Mental Component Summary (MCS) scores did not significantly differ from those of the general population. In contrast, the age- and gender-adjusted Physical Component Summary (PCS) scores were significantly lower than the general population starting in the fourth decade of life. Musculoskeletal diseases were most prevalent and had the greatest impact on the PCS scores. Two-thirds of this cohort had undergone at least one operation. Only musculoskeletal procedures were significantly associated with PCS and MCS scores. The functional health status of adults with achondroplasia, as measured by the SF-36, is not drastically reduced in comparison with that of the general U.S. population. Am. J. Med. Genet. 78:30–35, 1998. © 1998 Wiley-Liss, Inc.     

Epidemiology of achondroplasia: A population‐based study in Europe

Achondroplasia is a rare genetic disorder resulting in short‐limb skeletal dysplasia. We present the largest European population‐based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991–2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14–4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011–2015 vs. 36% in 1991–1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia.     

Birth prevalence of achondroplasia: A systematic literature review and meta‐analysis

Achondroplasia is a genetic disorder that results in disproportionate short stature. The true prevalence of achondroplasia is unknown as estimates vary widely. This systematic literature review and meta‐analysis was conducted to better estimate worldwide achondroplasia birth prevalence. PubMed, Embase, Scielo, and Google Scholar were searched, complemented by manual searching, for peer‐reviewed articles published between 1950 and 2019. Eligible articles were identified by two independent researchers using predefined selection criteria. Birth prevalence estimates were extracted for analysis, and the quality of evidence was assessed. A meta‐analysis using a quality effects approach based on the inverse variance fixed effect model was conducted. The search identified 955 unique articles, of which 52 were eligible and included. Based on the meta‐analysis, the worldwide birth prevalence of achondroplasia was estimated to be 4.6 per 100,000. Substantial regional variation was observed with a considerably higher birth prevalence reported in North Africa and the Middle East compared to other regions, particularly Europe and the Americas. Higher birth prevalence was also reported in specialized care settings. Significant heterogeneity (Higgins I² of 84.3) was present and some indication of publication bias was detected, based on visual asymmetry of the Doi plot with a Furuya‐Kanamori index of 2.73. Analysis of pooled data from the current literature yields a worldwide achondroplasia birth prevalence of approximately 4.6 per 100,000, with considerable regional variation. Careful interpretation of these findings is advised as included studies are of broadly varying methodological quality.