Surprisingly good outcome in antenatal diagnosis of severe hydrocephalus related to CCDC88C deficiency

Non-syndromic congenital hydrocephalus is aetiologically diverse and while a genetic cause is frequently suspected, it often cannot be confirmed. The most common genetic cause is L1CAM-related X-linked hydrocephalus and that explains only 5%–10% of all male cases. This underlines a current limitation in our understanding of the genetic burden of non-syndromic congenital hydrocephalus, especially for those cases with likely autosomal recessive inheritance. Additionally, the prognosis for most cases of severe congenital hydrocephalus is poor, with most of the surviving infants displaying significant intellectual impairment despite surgical intervention. It is for this reason that couples with an antenatal diagnosis of severe hydrocephalus are given the option, and may opt, for termination of the pregnancy. We present two families with CCDC88C-related recessive congenital hydrocephalus with children who had severe hydrocephalus. Those individuals who were shunted within the first few weeks of life, who did not require multiple surgical revisions, and who had a more distal truncating variant of the CCDC88C gene met their early childhood developmental milestones in some cases. This suggests that children with CCDC88C-related autosomal recessive hydrocephalus can have normal developmental outcomes under certain circumstances. We recommend CCDC88C analysis in cases of severe non-syndromic congenital hydrocephalus, especially when aqueduct stenosis with or without a medial diverticulum is seen, in order to aid prognosis discussion.     

VATER and hydrocephalus: distinct syndrome?

VACTERL association with hydrocephalus is rarely reported, and is thought to be an autosomal recessive uniformly lethal disorder distinct from the VATER association. We have observed 3 patients in a 12-month period with hydrocephalus due to aqueductal stenosis, in addition to vertebral anomalies (3/3), anal anomalies (3/3), cardiac anomalies (3/3), tracheoesophageal fistula (1/3), renal anomalies (3/3), limb anomalies (3/3), single umbilical artery (2/3), hypospadias (1/3), and cryptorchidism (1/2). Chromosomes were normal in all cases. Although one patient died in the neonatal period due to respiratory failure, 2 have survived (30 months and 19 months) with good neurological outcome following early neurosurgical treatment. Although delayed in motor development, both are interactive, social, and continue to make developmental progress. Appropriate surgical treatment, including early ventriculoperitoneal shunting, allowed for the survival of 2 patients with an unexpectedly good outcome. Our experience suggests that the extremely poor prognosis previously ascribed is not universal. We caution against labeling this syndrome as a uniformly lethal, developmentally devastating disorder.     

The Prevalence of Autoimmune Disorders Among Patients With Primary Ovarian Failure*

ABSTRACT: Eighty-one patients who had a diagnosis of primary ovarian failure were studied to determine its possible association with autoimmune disorders. All 81 patients displayed 46, XX chromosome complements. On ovarian biopsy, either few or no follicles were demonstrated in 79 patients, and, in two patients, primordial follicles were more abundant. The two patients with a large number of primordial follicles had normal function of other endocrine organs; however, 15 of the 79 patients demonstrating few or no ovarian follicles had associated failure of other endocrine glands, and one patient had myasthenia gravis. Thirteen of these 15 patients sought treatment because of secondary amenorrhea, the age at onset ranging from 11 to 34 years. Of the 81 patients, 11 had primary amenorrhea and 70 had secondary amenorrhea. Among the 79 patients with few or no ovarian follicles, endocrine glandular failure, in addition to ovarian failure, was found in two patients with primary amenorrhea and in 13 patients with secondary amenorrhea. The association of polyglandular failure syndrome and primary ovarian failure, along with demonstration of a lymphocytic infiltrate in ovaries and circulating antibodies in sera of women with premature ovarian failure, suggests that an autoimmune mechanism may be a cause of primary ovarian failure in some cases.     

Acute symptomatic hydrocephalus in Listeria monocytogenes meningitis.

Listeria monocytogenes meningitis appears to have increased in incidence. Although most reported cases of listeriosis involve the central nervous system, brain computed tomography is usually normal. Hydrocephalus is a common complication of tuberculous meningitis, which has a high prevalence in Taiwan. However, patients with L. monocytogenes meningitis rarely develop the complication of symptomatic hydrocephalus. We report a patient with L. monocytogenes meningitis who presented with persistent alteration of consciousness after appropriate antimicrobial therapy. Follow-up brain computed tomography revealed acute hydrocephalus. An Ommaya reservoir was implanted, and daily drainage of the cerebrospinal fluid was performed. The patient improved gradually and his mental status recovered completely 4 days later. This case should remind physicians to be aware of the possible occurrence of hydrocephalus in L. monocytogenes meningitis and that prompt cerebrospinal fluid drainage may achieve a good outcome.     

Endoscopic surgery for obstructive hydrocephalus

Endoscopic surgery is popular in the neurosurgical field. The purpose of this study was to determine the role of endoscopy in obstructive hydrocephalus. From 1989 to 1999, we performed 81 endoscopic third ventriculostomies and 10 septostomies. Seventy-one of 81 operations were performed with endoscopic third ventriculostomy alone and 10 patients had endoscopic third ventriculostomy and ventriculoperitoneal shunt simultaneously. Age distribution varied from 2 months to 62 years of age. Our selection criteria included aqueductal stenosis (39 patients) and obstructive hydrocephalus due to tumor or cyst (42 patients). The most common candidate for endoscopic septostomy was atresia of the foramen of Monro (4 patients). Endoscopic septostomy was also performed to simplify shunting in patient; with multiseptated ventricle due to shunt infection, germinoma, thalamic tumor, craniopharyngioma, cyst and brain abscess. Sixty-five of 71 patients who were treated with endoscopic third ventriculostomy alone showed successful results (91.5%). However, 6 patients had unsatisfactory results and they needed a ventriculoperitoneal shunt. With no mortality, transient surgical complications were observed in 7 patients: 2 transient diabetes insipidus from electrical injury to the pituitary stalk, 1 epidural hematoma from sudden drainage of CSF, 1 delayed intraventricular hemorrhage. 2 obstruction of fenestration site and 1 transient memory disturbance from injury to the fornix. Endoscopic septostomy was useful in simplifying shunting in all cases with complicated hydrocephalus. Endoscopic surgery is straightforward and effective in appropriately selected cases with obstructive by drocephalus.     

A novel computer-assisted surgical technique for revision total knee arthroplasty

Revision total knee arthroplasty (RTKA) is a skill-demanding intervention presenting several technical challenges to the surgeon due to bone deficiencies and lack of anatomical references. Computer-assisted navigation systems can potentially solve these problems. An innovative computer-assisted surgical technique for RTKA is presented. The system is image free. Based on anatomical landmarks acquired on the patient, the system automatically plans the intervention, and provides the surgeon with tools to analyse and modify the proposed plan and to accurately reproduce it on the patient. Although we performed few cases with this navigated procedure, early results obtained demonstrated to be very promising.     

Choroid plexus hyperplasia and chromosome 9p gains

Choroid plexus hyperplasia leading to communicating hydrocephalus is a rare disorder with only 24 patients reported so far in the literature. Furthermore, genetic information is only available for six of these cases: In one patient the condition was associated with trisomy 9p, in one patient with trisomy 9 mosaicism and in three patients with tetrasomy 9p. Here, we describe four additional patients with choroid plexus hyperplasia leading to various levels of hydrocephalus, and gain of the entire chromosome 9p region: Three with trisomy 9p and one with tetrasomy 9p. The three patients with trisomy 9p were siblings. Normal karyotypes were identified in the lymphocytes of the parents. Likely one of the parents is a mosaic for a cell line with trisomy 9p in the gonads. We demonstrate the importance of correctly diagnosing choroid plexus hyperplasia as the cause of hydrocephalus in patients with chromosome 9p gain since ventriculoperitoneal shunting is likely to fail due to intolerable formation of ascites.     

枣庄地区200例原发闭经患者的细胞遗传学分析

目的探讨原发闭经患者与细胞染色体异常的关系。方法选择在我院就诊的原发闭经患者200例,对每例患者进行外周血培养、染色体核型分析和妇科检查。结果在200例原发闭经患者中,检查出核型异常90例,异常核型检出率为45%（90/200）。在检出的异常核型中,Turner综合征患者48例,占53.3%（48/90）;46,XY 19例,占21.1%（19/90）;嵌合体/染色体结构异常23例,占25.6%（23/90）。结论性染色体结构或数目异常,可导致患者身材矮小、性腺发育不全、两性畸形、不孕、闭经等临床表现。通过细胞染色体核型分析,不仅为原发闭经患者寻找病因提供了理论依据,而且有利于对患者的治疗进行科学指导。     

广州地区176例闭经患者的细胞遗传学分析

目的探讨细胞遗传水平上原发性闭经和继发性闭经患者的发病机理。方法 156例原发性闭经患者,20例继发性闭经患者的外周血进行培养、制片、烘烤、胰酶消化和染色。每例标本观察20个核型,分析3～5个核型。如果遇到嵌合体,观察100例。结果在176例患者中,检测出48例染色体核型异常患者,异常核型率为27.27%,主要为X染色体数目异常和45,XO嵌合体,包括14例45,XO,19例45,XO嵌合体,5例X染色体结构异常,6例46,XY。156例原发性闭经患者中检测出46例异常核型,而在20例继发性闭经患者中检测出2例异常核型。结论染色体异常是引起原发性闭经和继发性闭经的重要原因,对闭经病人进行染色体检测对确定其病因和治疗是必要的。     

73例原发性闭经患者细胞遗传学病因分析

目的探讨厦门地区原发性闭经患者细胞遗传学的主要特征及性染色体异常对性腺发育的影响。方法 73例原发性闭经患者经常规妇科检查、B超及内分泌功能检查后,采用外周血淋巴细胞培养进行细胞遗传学分析。结果 73例原发性闭经患者中检出染色体正常核型52例,占71.2%,异常核型21例,占28.8%,包括性染色体数目、结构异常及嵌合体。结论染色体异常是导致原发性闭经的主要原因,对闭经患者进行染色体检查,明确闭经原因,及早对症治疗有重要意义。     

Ramichloridium mackenziei brain abscess: report of two cases and review of the literature.

We report two cases of brain abscesses caused by Ramichloridium mackenziei, a neurotropic dematiaceous fungus that seems to be geographically restricted to the Middle East. One of the patients had chronic myelomonocytic leukemia but did not receive any chemotherapeutic agents. The other patient was a normal host. Both cases had a fatal outcome despite aggressive antifungal therapy and surgical intervention. Herein, we review all previously described cases in the literature, and discuss the epidemiology, mycology and histopathology of this life-threatening organism.     

细胞遗传学检查在诊断闭经患者中的作用

目的 分析闭经患者的染色体核型,了解闭经与染色体异常的相关性,为临床治疗提供科学依据。方法 对158例闭经患者进行外用血淋巴细胞染色体棱型分析。结果 158例患者中有染色体异常者40例,占受检者25.3％(40/158)。原发性闭经患者中染色体异常检出率26.6%(33/124);继发性闭经患者中检出率为20.6％(7/34),染色体异常类型包括:X染色体数目异常13例,结构异常5例,嵌合体11例,含Y染色体13例。结论 性染色体决定着女性性腺及生殖器官的发育,性染色体异常是导致闭经的重要原因。对于闭经患者常规行染色体检查是必要的。     

闭经患者的分子遗传学分析

目的探讨闭经患者与细胞染色体异常及其相关的SRY基因的关系.方法选择在我院就诊的闭经患者197例,其中原发性闭经141例、继发性闭经56例,对每例患者进行淋巴细胞染色体检查与妇科检查,对含有Y染色体的患者或先天性无子宫、无阴道的患者进行SRY检测;选16例SRY( )的患者进行SRY基因序列分析.结果原发性闭经组,性染色体数目和/或结构异常患者39例,常染色体异常1例,SRY( )12例,其中2例患者SRY基因分析有突变;继发性闭经组,性染色体数目和/或结构异常患者10例,常染色体异常1例,SRY( )2例,1例SRY基因分析提示有突变.结论结合临床体征和染色体检查、SRY监测,不仅为闭经患者寻找病因提供理论依据,而且有利于指导治疗.     

Primary cutaneous leiomyosarcoma: a histological and immunohistochemical study of 4 cases

Primary cutaneous leiomyosarcoma is an uncommon malignant neoplasm with a predilection for the lower extremities. A retrospective study of 4 cases was undertaken to analyse the clinicopathological characteristics and immunohistochemical profile of these neoplasms with emphasis on prognosis. Two male and 2 female patients aged between 49 and 80 years presented with painless tumours involving the lower lip, the chin, the scrotum and the shoulder. Histological examination of the initial biopsy specimen established a diagnosis of cutaneous leiomyosarcoma. All cases co-expressed smooth muscle actin and vimentin regardless of primary tumour site. Wide surgical excision of the tumour was performed in only 3 cases, and the remaining patient refused further treatment. Of the patients undergoing surgical intervention, local recurrence occurred in one case. No metastases were observed. Long-term follow-up of patients with cutaneous leiomyosarcoma is mandatory to detect local recurrence and distant metastases that can occur even years after the initial excision.     

A new variant of the cytochrome P450c17 (CYP17) gene mutation in three patients with 17 α-hydroxylase deficiency

A new CYP17 gene abnormality was found in three Japanese patients with 17α-hydroxylase deficiency (17OHD). These patients were children from consanguineous marriages, but from two apparently unrelated families: one patient with 46, XY karyotype, and two siblings with 46, XX and 46, XY karyotypes. They were all raised as girls and presented with amenorrhea, eunuchoid appearance and hypertension. Gene analysis revealed two base-pair (TG) deletion in exon 5 (codons 300, 301) of the CYP17 gene. This deletion could be expected to alter the reading frame resulting in the lack of a haem-binding region (Cys 442) due to a premature stop codon at position 333. This small mutation may account for the patients' clinical manifestations of 17OHD.     

Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6

We describe two patients who suffered transient neonatal diabetes mellitus (TDNM), due to paternal isodisomy of chromosome 6. One patient, now 5 years old, had severe intra-uterine growth retardation, but recovered normal growth parameters. The other patient, currently 12 years old, had a normal birth weight but showed impaired post-natal growth; in addition to TNDM the patient presented with cardiac and thyroid abnormalities. These cases may suggest that the clinical phenotype of TNDM is more variable than previously believed. The contribution of genetic and epigenetic factors needs to be determined to elucidate the phenotype-genotype relationships of this disease.     

Surgical management of Chiari malformation type 1 associated to MCAP syndrome and study of cerebellar and adjacent tissues for PIK3CA mosaicism

BackgroundSubjects with Megalencephaly-Capillary Malformation-Polymicrogyria syndrome (MCAP) can present with a Chiari Malformation Type 1 and resulting alterations in cerebrospinal fluid (CSF) dynamics, which may require surgical treatment. The aim of this paper is to describe the features of children with MCAP who underwent surgical decompression for CM1, and to explore the PIK3CA variant allele frequency (VAF) identified in cerebellar parenchyma and other adjacent structures.MethodsThis study reviewed two cases of children with CM1 and MCAP who underwent surgical decompression treatment. These two cases were part of a national cohort of 12 MCAP patients who had CM1, due to their surgical eligibility. Tissue samples were obtained from the cerebellar tonsils and adjacent anatomical structures during the surgical procedures. Samples were then subsequently analyzed for PIK3CA postzygotic variants.ResultsIn both cases, alterations in CSF dynamics, specifically hydrocephalus and syringomyelia, were observed and required surgical treatment. PIK3CA targeted sequencing determined the VAF of the postzygotic variant in both cerebellar and adjacent bone/connective tissues.DiscussionThe recognition of a CM1 comorbidity in MCAP patients is of paramount importance when considering personalized treatment options, especially because these patients are at higher risk of developing complications during surgical decompression surgery. The variable PIK3CA VAF identified in the different analyzed tissues might help explain the heterogeneous nature and severity of anomalies observed in the volume of the posterior fossa structures in MCAP patients and associated CSF and venous disorders.     

Sudden death in rheumatoid arthritis from vertical subluxation of the odontoid process

Rheumatoid arthritis is a chronic, multisystem disease that causes significant morbidity and early mortality. A common source of morbidity in severe rheumatoid arthritis is involvement of the cervical spine. Sudden death due to subluxation of the odontoid process into the medulla oblongata is a dramatic but rare complication. We report the case of a patient who died suddenly. Computerized tomography scan, autopsy, and clinical findings were correlated. Studies of cervical involvement in rheumatoid arthritis were analyzed for cases of vertical subluxation. The case reports of sudden deaths and patients treated for vertical subluxation were reviewed; they revealed a trend toward surgery in patients with neurological abnormalities. However, a comparison of clinical outcome does not demonstrate improved survival with surgical intervention. Randomized trials comparing surgical with nonsurgical therapy are needed.     

Acrocephalosyndactyly with Hydrocephalus and Dextrocardia in a Nigerian Child

A rare case of dextrocardia and hydrocephalus in a patient with acrocephalosyndactyly is reported. In the patient presented here, barium meal studies showed the gastrointestinal tract to be in normal position. There was no evidence of cardiac disease but the patient showed some neurological retardation at age nine months.     

Ring chromosome 6 in three fetuses: case reports, literature review, and implications for prenatal diagnosis

Prenatal and postnatal findings in three fetuses with a ring chromosome 6 are presented, and the literature of this rare cytogenetic disorder is reviewed. The described fetuses illustrate the broad spectrum of the clinical manifestation of ring chromosome 6. In one fetus, the disorder was diagnosed incidentally by a routine amniocentesis due to advanced maternal age. The other two fetuses were hydrocephalic and had other congenital anomalies. Remarkably, the ring chromosome 6 tends to disappear in cultured amniotic fluid cells; karyotyping revealed complete or nearly complete monosomy 6. In contrast, the ring was preserved in high proportions of fetal leukocytes. Postnatal growth retardation is the only consistent finding of this chromosomal disorder. Maternal age is not significantly above average. An additional review of 20 literature cases revealed a striking tendency to hydrocephalus, either due to deficient brain growth or secondary to an aqueductal stenosis. Children with hydrocephalus and ring chromosme 6 tend to display facial dysmorphism and may have additional malformations, growth failure, eye anomalies, and seizures. In contrast, there are two reports on children with a ring chromosome 6 who had short stature, normal appearance, and a normal or almost-normal psychomotor development. In such patients at the mild end of the clinical spectrum, the phenotype is basically restricted to what Kosztolányi. [1987: Hum Genet 75:174-179] delineated as "ring syndrome," comprising "severe growth failure without major malformations, without a specific deletion syndrome, with only a few or no minor anomalies, and mild to moderate mental retardation." This "ring syndrome" is considered to occur independently of the autosome involved in the ring formation. The overall impression from our cases and from the literature review of cases with ring chromosome 6 is that the karyotype-genotype correlation is poor. This makes prognostic counseling of parents difficult and unsatisfactory. Serial targeted ultrasound examinations, especially of the brain, are decisive factors in elucidating the prognosis.