指甲-髌骨综合征一个家系报告

指甲-髌骨综合征(nail-patella syndrome,NPS)又名遗传性指甲-髌骨发育不良,是包括指甲、髂骨角、膝和肘部四联畸形及多系统受累的家族遗传性疾病[1].国外报道发病率约为1/50 000[2],国内鲜有报道.我们报道1个4代6例的NPS家系.     

Nail-patella syndrome: long term evolution

Nail-patella syndrome is a rare dysplasia characterized by a typical tetrad: hypoplasic nails, hypoplasic or absent patella, radial head dislocation and iliac horns. We review eight patients, four men and four women, aged from 20 to 70 years. The main complaint at consultation was with their knees due to patellar instability and pain. Five of them required surgical treatment due to patellar dislocation and three patients were not treated. The Krogius-Lecène procedure was performed in four patients with a good result following the Insall classification of pain and instability and with an average follow-up of 24 years (range, 18-28 years). Patellectomy was performed in the eldest patient due to femoropatellar arthritis present at first consultation. No patients presented with elbow or nail disorders or with iliac horns.     

Diffuse pulmonary fibrosis and the Hermansky-Pudlak syndrome: clinical course and postmortem findings.

The Hermansky-Pudlak syndrome consists of albinism, platelet function defect, pigment laden macrophases and, on occasions, pulmonary fibrosis. The clinical course and postmortem findings of a patient with pulmonary fibrosis which mimicked cryptogenic fibrosing alveolitis are reported. Histological examination revealed a chronic inflammatory infiltrate of pigment laden microphages.     

Familial ureteral abnormalities syndrome: genomic mapping, clinical findings

Abnormal development of the ureter during embryogenesis, when occurring in multiple family members, appears to be a genetically determined defect with autosomal dominant inheritance and high penetrance, which can lead to significant kidney damage, renal failure, and death. We have studied 48 individuals within a large kindred in which ureteral-related abnormalities (including vesicoureteral reflux, ureteropelvic junction obstruction, duplicated ureters, and medullary sponge kidney) were segregated. Family members who had not had previous diagnostic studies were evaluated for presence or absence of ureteral abnormalities and we attempted to map the locus for this familial ureteral abnormalities syndrome (FUAS). These studies identified 11 asymptomatic individuals, previously assumed to be unaffected, with minor abnormalities. When linkage analysis between the inheritance of ureteral abnormalities and six marker loci glyoxalase I (GLO-1), major histocompatibility antigens (HLA-A, B, and DR/DQ), D6S288, and factor XIII antigen (F13A1) on the short arm of chromosome 6 was performed, the lod scores significantly rejected linkage over a 77.1-cM distance. These findings are in contrast to previous data suggesting linkage between the presence of ureteral abnormalities and HLA, and indicate the possibility of genetic heterogeneity of FUAS. Received April 29, 1997; received in revised form September 15, 1997; accepted September 22, 1997     

Ehlers-Danlos syndrome type VII: clinical features and molecular defects

We evaluated the clinical features, molecular defects, and problems associated with the management of two patients who had type-VII Ehlers-Danlos syndrome and reviewed the cases of eighteen patients with this condition who had been reported on previously. The typical clinical features associated with this syndrome include bilateral congenital dislocation of the hip; severe generalized hypermobility of the joints; multiple dislocations of joints other than the hip; muscular hypotonia; and hyperelasticity, fragility, and a doughy texture of the skin. Collagen and DNA analyses demonstrated that both of our patients had type-VIIB Ehlers-Danlos syndrome, which is caused by heterozygous new mutations of the COL1A2 gene that encodes the proalpha2(I) chain of type-I procollagen. The obligatory GT dinucleotide at the splice donor site of intron 6 was altered in both of our patients: one patient (Case 1) had an A substitution of the G nucleotide, and the other patient (Case 2) had a C substitution of the T nucleotide. Abnormal splicing resulted in the loss of the exon 6-encoded N-telopeptide, which includes the N-proteinase cleavage site. Despite multiple operative procedures, one of our patients, who was thirty-seven years old at the time of the most recent follow-up, continued to have persistent subluxation of the right hip and osteoarthritis of the left hip. Closed reduction of the dislocated hips, regardless of the type of immobilization used, was unsuccessful in all twenty patients. The results of open reduction were improved when capsulorrhaphy was combined with iliac or femoral osteotomy, or both.     

雄激素不敏感综合征手术治疗及探查结果分析

目的探讨雄激素不敏感综合征(androgen insensitivity syndrome,AIS)患者的性腺切除途径及其临床病理特点。方法回顾性分析1984年6月至2009年3月北京协和医院诊治的74例AIS患者的性腺切除途径、术后病理结果及性腺位置等特点。结果 74例患者均手术切除双侧性腺。其中完全型雄激素不敏感综合征(CAIS)48例,平均年龄22.0岁,有家族史者3例(6.25%),术中探查发现25例双侧性腺均位于盆腔(52.1%),13例双侧性腺均位于腹股沟内(27.1%);不完全型雄激素不敏感综合征(IAIS)26例,平均年龄16.5岁,有家族史者5例(19.2%),术中探查发现3例双侧性腺均位于盆腔内(11.5%),9例双侧性腺均位于腹股沟内(34.6%),10例双侧性腺均为于大阴唇中(38.5%)。CAIS患者中,开腹切除性腺21例,腹腔镜下性腺切除27例;IAIS患者中,9例开腹切除性腺,7例腹腔镜下性腺切除,10例经会阴切除性腺。术后病理证实睾丸肿瘤的发生率为18.9%,恶性肿瘤占4.1%。结论 IAIS的患者就诊和手术的平均年龄均较CAIS患者年轻,IAIS的患者较CAIS患者有家族史的多。双侧性腺位于盆腔的患者中CAIS多于IAIS,性腺降至腹股沟和大阴唇内的患者中IAIS多于CAIS。AIS患者性腺肿瘤发生率较高,一旦确诊应尽早手术治疗;可参考性腺的位置采用经会阴及腹腔镜微创手术切除性腺。     

Chronic prostatitis/pelvic pain syndrome: MRI findings and clinical correlations

We aimed to evaluate whether pelvic magnetic resonance imaging (MRI) could play a role in better assessing chronic pelvic pain syndrome. We evaluated 44 male patients (median 41 aged) with a clinical history of painful pelvic symptoms, lasting for at least three of the previous 6 months, associated with urinary, anorectal and sexual disorders in the absence of bacterial prostate infection. All these patients underwent ultrasound (US) and MRI evaluation of the pelvis. Prostate imaging findings, such as gland morphology evaluated by US and prostatic signal intensity on MRI, appeared normal in the majority of patients (38/44; 82%). Extraparenchymal alterations were found in 28 patients (63.6%); the most frequent was the dilatation of periprostatic vein plexus (20/28; 71.4%), significantly correlated to chronic pelvic pain syndrome (p = 0.0013), regardless of different clinical presentations. This finding was tested in a control group of 90 patients, demonstrating an excellent specificity (97%), good positive predictive value (87%) and diagnostic accuracy (80%). MRI confirmed its high capability in evaluating prostatic and extraprostatic structures. Periprostatic vein dilatation, which identified approximately two‐thirds of the patients with chronic pelvic pain syndrome using pelvic MRI, significantly correlated to chronic pelvic pain syndrome, independently of patient age, symptoms and prostatic volume.     

脊髓栓系综合征术后尿动力学的测定及临床意义

目的　探讨脊髓栓系综合征 (TCS)患儿术后尿动力学表现及其临床意义。　方法　对4 0例TCS患儿术后行尿动力学测定 ,分析影响术后下尿路症状改善及尿动力学结果的因素。　结果　 4 0例患儿中 5例手术前后均无下尿路症状 ,术前 35例有尿失禁伴夜间遗尿者中术后 8例尿失禁减轻 ,2 4例无变化 ,3例加重。尿动力学测定示膀胱顺应性降低 2 1例 ,剩余尿增加 2 1例 ,逼尿肌无力19例 ,膀胱容量减小 15例 ,逼尿肌反射亢进 13例 ,逼尿肌括约肌协同失调 8例 ,漏尿点压力 >4 0cmH2 O (1cmH2 O =0 .0 98kPa) 4例。自述无下尿路症状 5例中 ,膀胱逼尿肌反射亢进 2例 ,逼尿肌括约肌协同失调 2例 ,基本正常 1例。术后尿失禁改善率原发性TCS(2 8.6 % ,8/ 2 8)高于继发性(0 % ,0 / 7,P =0 .0 4 8) ,非脂肪瘤型 (10 0 % ,3/ 3)高于脂肪瘤型者 (15 .6 % ,5 / 32 ,P =0 .0 0 4 ) ,脊膜膨出型 (36 .4 % ,8/ 2 2 )高于脊髓脊膜膨出型 (0 % ,0 / 6 ,P =0 .0 4 7) ,出生时无泌尿系症状者 (80 % ,4 / 5 )高于出生时有泌尿系症状者 (17.4 % ,4 / 2 3,P =0 .0 19)。尿动力学测定示术后原发性TCS逼尿肌反射亢进的发生率 (2 4 .2 % ,8/ 33)低于继发性TCS(71.4 % ,5 / 7,P =0 .0 15 ) ,非脂肪瘤型 (12 .5 % ,1/ 8)低于脂肪瘤型TCS(5 6 .3%     

Autosomal recessive Alport syndrome: an in-depth clinical and molecular analysis of five families.

BACKGROUND: Alport syndrome (ATS) is a progressive inherited nephropathy characterized by irregular thinning, thickening and splitting of the glomerular basement membrane (GBM) often associated with hearing loss and ocular symptoms. ATS has been shown to be caused by COL4A5 mutations in its X-linked form and by COL4A3 and COL4A4 mutations in its autosomal forms. METHODS: Five families with a suspicion of ATS were investigated both from a clinical and molecular point of view. COL4A3 and COL4A4 genes were analysed by DHPLC. Automated sequencing was performed to identify the underlying mutation. RESULTS: Molecular analysis indicated that in all 5 cases the correct diagnosis was autosomal recessive ATS. In three families in which parental consanguinity clearly pinpointed to autosomal recessive ATS, we found COL4A4 homozygous mutations in two of them and COL4A3 homozygous mutation in the other one. In the remaining two families a differential diagnosis including X-linked ATS, autosomal recessive ATS and thin basement membrane nephropathy was considered. The molecular analysis demonstrated that the probands were genetic compounds for two different mutations in the COL4A4 gene pinpointing to the correct diagnosis of autosomal recessive ATS. CONCLUSIONS: A clinical evaluation of probands and their relatives of the five families carrying mutations in either the COL4A3 or the COL4A4 gene was carried out to underline the natural history of the autosomal recessive ATS. In addition, this paper stresses the complexity of the clinics and genetics of ATS and how a correct diagnosis is based on a combination of: (i) an in-depth clinical investigation; (ii) a detailed formal genetic analysis; (iii) a correct technical choice of the gene to be investigated; (iv) a correct technical choice of the family member to be included in the mutational screening. A correct diagnosis is the basis for an appropriate genetic counselling dealing with both the correct prognosis and the accurate recurrence risk for the patients and family members.     

Clinical and molecular findings in a family with the carbonic anhydrase II deficiency syndrome

Carbonic anhydrase II (CA2) deficiency syndrome is an autosomal recessive disorder leading to osteopetrosis, renal tubular acidosis, and cerebral calcifications. Affected members of an Arab family with the CA2 deficiency syndrome carried the Egyptian mutation in CA2, i.e., c.191 del A, H64fsX90. One affected member, homozygote for the mutation, developed primary pulmonary hypertension. Primary pulmonary hypertension was never described before in patients with this unique syndrome. The likelihood of both occurring randomly in a single individual is very low. We therefore speculate that there might be a possibility of an etiologic link between these entities.     

Thyroid carcinoma. Correlation between clinical and pathological findings.

Our survey of 146 cases of thyroid carcinoma showed the following points: (a) in 20% of the cases the gland was diffusely enlarged without nodules; (b) in 35% of 34 cases, thyroid carcinoma was located in areas other than the "cold" zones; (c) multiple foci of carcinoma were found in 67% of cases with total or subtotal thyroidectomy and in 33% of cases with partial thyroidectomy; (d) anaplastic carcinomas (13% of cases) occurred in patients of all ages, 29% of them in patients younger than 30 years.     

Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy associated with defective regulation of the alternative complement pathway. The prognosis for patients with aHUS is poor, and plasma exchange represents the first-line therapy. Eculizumab is a humanized monoclonal anti-C5 antibody that prevents the activation of the terminal complement pathway. Here, we report the case of a 9-year-old girl with frequent relapsing aHUS due to heterozygous factor H mutation who was initially treated with plasma exchange three times per week with 150% plasma exchange volume. This treatment frequently caused allergic reactions and school absences. Because any reduction in the frequency of plasma exchange immediately induced relapses of the aHUS, treatment with eculizumab, 600 mg every 2 weeks, was started and plasma exchange completely stopped. On this drug regimen the patient showed no evidence of disease activity during a period of more than 24 months. Renal function improved, proteinuria disappeared, the number of antihypertensive medications could be decreased, and the quality of life increased substantially. The inhibition of the terminal complement pathway by eculizumab was also confirmed by renal biopsy, which showed the absence of thrombotic microangiopathy 2 months after the initiation of eculizumab therapy. This case illustrates the long-term favorable outcome of aHUS with eculizumab treatment.