A case of 8q22.1 microdeletion without the Nablus mask-like facial syndrome phenotype.

Nablus mask-like facial syndrome (NMLFS) has been reported in six patients with a recognizable facial appearance, along with other clinical features. Microdeletions of 8q21.3-8q22.1 were identified in all six cases, with the deleted region in common being 8q22.1 (2.78 Mb in length). In this report, we describe a child with speech delay and features of an autistic spectrum disorder and with a 1.6 Mb deletion of 8q22.1. The deletion has significant chromosomal overlap with previously reported examples of NMLFS, but our patient lacks the clinical features noted in the published cases.

An algorithm for the prenatal detection of chromosome anomalies by QF-PCR and G-banded analysis.

OBJECTIVE: The objective of this study was to examine in theory the clinical utility of a prenatal algorithm that uses rapid aneuploidy detection in all cases and G-banded analysis for selected cases (RAD/G algorithm). METHODS: Over a 4-year period, amniotic fluid samples were prospectively assigned into RAD (limited analysis) or RAD/G (intensive analysis) categories based upon the likelihood of the fetus having a chromosome anomaly. The samples were cultured and analyzed by standard cytogenetic methods. The rates of clinically significant chromosomal anomalies potentially undetectable by the RAD/G algorithm were calculated. RESULTS: The karyotype was normal in 3861/4054 (95.24%) cases and abnormal in 193 (4.76%). From these data, the detection rate of the RAD/G algorithm was 87.6% if all abnormalities detected by G-banding were taken into consideration and 97.6% if abnormalities having reduced predictive value were excluded (balanced rearrangements and most mosaic cases). CONCLUSIONS: Compared to G-banding alone, the RAD/G algorithm has a reduction in sensitivity due to undetectable abnormalities and mosaicism in the RAD group. However, it provides a rapid and inexpensive alternative to traditional G-banded analysis, and might be more appropriate for patients with uncomplicated, low risk pregnancies.

Face-brain asymmetry in autism spectrum disorders.

The heterogeneity of autism spectrum disorders (ASDs) confounds attempts to identify causes and pathogenesis. Identifiable endophenotypes and reliable biomarkers within ASDs would help to focus molecular research and uncover genetic causes and developmental mechanisms. We used dense surface-modelling techniques to compare the facial morphology of 72 boys with ASD and 128 first-degree relatives to that of 254 unrelated controls. Pattern-matching algorithms were able to discriminate between the faces of ASD boys and those of matched controls (AUC=0.82) and also discriminate between the faces of unaffected mothers of ASD children and matched female controls (AUC=0.76). We detected significant facial asymmetry in boys with ASD (P<0.01), notably depth-wise in the supra- and periorbital regions anterior to the frontal pole of the right hemisphere of the brain. Unaffected mothers of children with ASD display similar significant facial asymmetry, more exaggerated than that in matched controls (P<0.03) and, in particular, show vertical asymmetry of the periorbital region. Unaffected fathers of children with ASD did not show facial asymmetry to a significant degree compared to controls. Two thirds of unaffected male siblings tested were classified unseen as more facially similar to unrelated boys with ASD than to unrelated controls. These unaffected male siblings and two small groups of girls with ASD and female siblings, all show overall directional asymmetry, but without achieving statistical significance in two-tailed t-tests of individual asymmetry of ASD family and matched control groups. We conclude that previously identified right dominant asymmetry of the frontal poles of boys with ASD could explain their facial asymmetry through the direct effect of brain growth. The atypical facial asymmetry of unaffected mothers of children with ASD requires further brain studies before the same explanation can be proposed. An alternative explanation, not mutually exclusive, is a simultaneous and parallel action on face and brain growth by genetic factors. Both possibilities suggest the need for coordinated face and brain studies on ASD probands and their first-degree relatives, especially on unaffected mothers, given that their unusual facial asymmetry suggests an ASD susceptibility arising from maternal genes.

Isodicentric Yp: prenatal diagnosis and outcome in 12 cases.

OBJECTIVES: 1. To present the prenatal cytogenetic findings and postnatal outcome of 12 cases with an isodicentric chromosome composed of the short arm of the Y chromosome.2. To review the literature and provide recommendations for cytogenetic analysis and counseling. METHODS: Prenatal and postnatal cytogenetic data and clinical findings of isodicentric Yp ascertained in six institutions were gathered and reviewed. RESULTS: Nine of the twelve cases were referred for advanced maternal age (AMA), one of which was a twin pregnancy with one twin having an increased nuchal translucency measurement. The remaining cases were referred owing to a family history of hemophilia and an abnormal maternal serum screen, respectively. Nine of these pregnancies resulted in the birth of a normal-appearing male infant with subsequent normal growth and psychomotor development. Follow-up ranged from birth to 7 years. In two cases, the pregnancy was terminated and the fetuses showed male external genitalia. In the case ascertained because of an increased nuchal translucency measurement, the prenatal diagnosis of 45,X was made. At birth, there were ambiguous genitalia, and postnatal cytogenetic studies found an isodicentric Yp. In 11 of the 12 cases, mosaicism was present. CONCLUSION: Our cases show that the prenatal finding of an isodicentric Yp, with or without 45,X mosaicism, is compatible with normal male phenotype in most cases, particularly in the absence of other anomalies. To ensure accuracy in cytogenetic reporting and prenatal counseling, the identification of a structurally abnormal or small Y chromosome, either alone or in the presence of 45,X colonies, should be followed immediately by confirmatory molecular cytogenetic investigations as well as by ultrasound determination of the phenotypic sex of the fetus.

Maternal serum screening in Ontario using the triple marker test.

OBJECTIVES: To summarise the experience and evaluate the performance of the Ontario maternal serum screening (MSS) programme. SETTING: The Ontario MSS programme between October 1993 and September 2000. METHODS: This study used information collected in the Ontario MSS database, which contains data on each screened pregnancy. In the Ontario MSS programme, women are screened between 15 and 20 weeks of gestation. The risk cut-off for Down's syndrome was >or= 1 in 385 at term and women with a serum alpha-fetoprotein >or= 2.2 multiples of the unaffected population median were defined as screen-positive for open neural tube defects. RESULTS: Between 1 October 1993 and 30 September 2000, 428410 women residing in Ontario were screened for open neural tube defects, and 423895 women were screened for Down's syndrome and trisomy 18. Approximately 48% of all pregnant women in the province had MSS. The uptake rate of amniocentesis following a positive Down's syndrome screening was 67%. Of 717 cases of Down's syndrome ascertained in the screened population, 531 were detected by MSS, giving a term detection rate (DR) of 70.6%, with a false-positive rate (FPR) of 7.2%. For neural tube defects, the DR was 72.7%, with a FPR of 2.0%. The screen also detected 50% of cases of trisomy 18 at term, with a FPR of 0.2%. Coincidentally, 113 cases of chromosome aneuploidies other than Down's syndrome and trisomy 18 were detected. DISCUSSION: In the Ontario MSS programme, MSS performed as expected in the detection of Down's syndrome, open neural tube defects and trisomy 18. MSS is an effective and practical method for large-scale second trimester screening for Down's syndrome, open neural tube defects and trisomy 18, and the MSS database is an extremely useful tool in monitoring the performance of this screen.

Trends in major risk factors for anal sphincter lacerations: a 10-year study.

OBJECTIVES: (1) To identify independent risk factors for anal sphincter laceration, (2) to determine the trend in rates of anal sphincter laceration over a 10-year period, and (3) to examine the impact of temporal trends in risk factors on anal sphincter laceration rates. METHODS: Population-based data were obtained from the Nova Scotia Atlee Perinatal Database, on 91 206 women who had a singleton vaginal live birth > or =500 g for the years 1988 to 1997. Risk factors for anal sphincter laceration were identified using stepwise logistic regression. A multivariate model was used to study temporal changes in laceration rates after controlling for changes in parity, episiotomy rates, operative vaginal deliveries, birth weight, prolonged second stage of labour, and other determinants. RESULTS: Nulliparity (relative risk [RR] = 6.97), occiput posterior position (RR = 2.44), non-vertex presentations (RR = 2.27), second stage > or =120 min (RR range = 1.47-2.02), delivery by an obstetrician (RR = 1.30), and birth weight > or =3000 g (RR range = 1.43-6.63) increased the risk of laceration. Instrument-assisted delivery involved risks that ranged from a 2-fold increase for a vacuum-assisted delivery (RR = 2.15) to a greater than 5-fold increase for a forceps delivery after an unsuccessful vacuum extraction (RR = 5.69). Episiotomy, particularly midline incisions, increased the risk of laceration (RR = 2.57). The risk of a sphincter laceration increased 2-fold from 1988 to 1997, despite controlling for risk factors. CONCLUSIONS: Sufficient evidence exists about the risk factors for anal sphincter laceration to permit modification of management of labour and delivery to minimize the risk of anal sphincter laceration. Increased awareness of the clinical importance of recognition and repair of anal sphincter laceration may explain the rising incidence.

Direct duplication of 8p21.3-->p23.1: a cytogenetic anomaly associated with developmental delay without consistent clinical features.

We report six cases in two families and a sporadic case with a direct duplication of region 8p21.3-->23.1. In one family, the duplication started in the mother and was transmitted to one son and one daughter. In the second family, the father was mosaic for the anomaly that was transmitted to his two daughters. The cytogenetic anomaly was initially described as an 8p+ with banding analysis and then delineated with fluorescence in situ hybridization (FISH) using whole-chromosome 8 painting, 8p specific painting, and 8p or 8p/8q subtelomeric probes. Deletion was not detected in the subtelomeric region of the abnormal chromosome 8 examined in one family and in the sporadic case. The phenotypic picture varies from normal to moderate mental retardation in the affected individuals. No consistent minor anomalies or congenital defects were observed among these cases. After comparing the chromosome region involved in our cases with those in others having direct or inverted duplications of 8p, it is thought that the segment 8p21.1-->21.3 might be the critical region for an 8p duplication syndrome. The parental origin of the duplication does not seem to impact its clinical significance.

Histologic examination of "fascia" used in colporrhaphy.

OBJECTIVE: To perform a histologic examination of tissue identified as fascia and used during colporrhaphy. METHODS: In patients undergoing primary anterior and posterior colporrhaphy, biopsies were taken from three surgically distinct vaginal tissues types: the wall, the "fascia," and areolar tissue. The biopsies were placed in formalin, identified numerically, and sent to pathology for staining with hematoxylin-eosin, Masson trichrome for collagen, Movat for elastin, and immunoperoxidase stain for actin in smooth muscle. Simultaneous photographs were taken of the biopsy sites. The histologic diagnosis was compared with the surgical diagnosis. RESULTS: A total of 60 samples were taken from five women. The specimens from two of these patients were disqualified. The pathologist made the following histologic diagnosis for each type of surgical specimen: vaginal wall, mucosa and underlying connective tissue; fascia, moderately dense connective tissue with smooth muscle; areolar tissue, loose connective tissue. The histologic appearance of the "fascia" was indistinguishable from the deeper aspects of the vaginal wall. It was composed of the same proportions of smooth muscle, elastin, and collagen. Using the histologic appearance as the "gold standard," the accuracy of the surgical diagnosis was: "vaginal wall," 12 of 12 (100%); "fascia," seven of 12 (58%); and "areolar tissue," eight of 12 (67%). CONCLUSIONS: The surgical "fascia" used during colporrhaphy consists of moderately dense connective tissue with smooth muscle similar to the deep aspects of the vaginal wall, is the same in both the anterior and posterior compartments, and is an artifact of the surgical dissection used to separate the vaginal wall from the underlying organs.

Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G-->C genotype.

Smith-Lemli-Opitz syndrome (RHS) (SLOS, OMIM 270400) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations of the 3beta-hydroxysterol Delta(7)-Delta(8)-reductase gene, DHCR7. We report a fetus with holoprosencephaly and multiple congenital anomalies who was homozygous for the IVS8-1G-->C mutation. Following termination of pregnancy, both the elevated amniotic fluid 7-dehydrocholesterol level and the DHCR7 mutations were demonstrated. Two other newborn infants with IVS8-1G-->C/IVS8-1G-->C genotype are described. This report illustrates a severe phenotypic extreme of SLOS associated with a null genotype, underscores the complex relationship between SLOS and holoprosencephaly, and discusses the possible pathogenetic mechanisms of the development of holoprosencephaly in SLOS.

External iliac artery laceration during tension-free vaginal tape procedure.

This is a case review of a patient who, during surgery for stress incontinence using the tension-free vaginal tape procedure, sustained a laceration to the right external iliac artery.

Recombinant Down syndrome: a case report and literature review.

We report a case of a child with features of Down syndrome (DS) but with an atypical karyotype. Initial chromosome analysis was 46,XX,dup(21q).ish 21(wcp21+). The father's chromosomes were normal. However, the mother was found to have mosaicism for a pericentric inversion of chromosome 21 (19/30 cells). The revised chromosome result of the child was 46,XX,rec(21)dup(21q)inv(21)(p12q21.1)mat. A literature review of similar cases (hereafter referred to as rec dup(21q)) was conducted to aid counselling about recurrence risks and the prognosis for this child. All previous reports of rec dup(21q) were secondary to a maternal pericentric inversion. Male carriers did not seem to be at risk of having offspring with the rec dup(21q), although the number of male carriers was limited. In those with rec dup(21q), the risk of congenital heart disease was similar to that of trisomy 21. In reported cases, the facial appearance was suggestive of Down syndrome but perhaps less striking. Although the data are limited, there is an indication the developmental disabilities and short stature are milder in those with rec dup(21q) compared to trisomy 21. These observations promote the concept that the region of chromosome 21 proximal to the duplication contains genetic information contributing to the expression of some features of Down syndrome.

Parturition and urinary incontinence in primiparas.

OBJECTIVE: To estimate the incidence and relative risk of postpartum urinary incontinence in primiparas. METHODS: Over 3 years (1996-1998), healthy nulliparas with no significant history of urinary tract abnormalities were prospectively enrolled. Power analysis indicated that 452 women must complete the study. Participants completed a questionnaire about urinary, fecal, and flatal incontinence. At 6 weeks' and 6 months' postpartum, the same questionnaire was mailed to participants. Statistical analysis consisted of chi-square and Fisher exact tests for nominal variables and analysis of variance and Kruskal-Wallis tests for interval variables. Logistic regression tested independence of variables. RESULTS: A total of 690 primiparas were enrolled in the study and 595 delivered at our hospital: 147 (25%) cesareans, 333 (56%) spontaneous vaginal deliveries, and 115 (19%) instrumental vaginal deliveries. Median birth weight was 3489 g. Urinary incontinence rate at 6 months was 26%. Vaginal delivery was associated with a higher incidence of urinary incontinence (relative risk, 2.8) compared with cesarean. Forceps delivery increased the risk of urinary incontinence (relative risk, 1.5) compared with spontaneous vaginal delivery. There was no significant difference between cesareans done before and during labor. None of the obstetric risk factors were independently significant. CONCLUSION: Cesarean delivery at any stage of labor reduces postpartum urinary incontinence. With multivariable analysis, obstetric risk factors are not significant.

Vaginal repair of a sigmoidocele.

Sigmoidocele is an uncommon accompaniment of pelvic prolapse. It is difficult to detect a sigmoidocele during clinical pelvic examination, and as a consequence a sigmoidocele may be unexpectedly encountered during vaginal repair of pelvic prolapse. The author has discovered and repaired a sigmoidocele during vaginal surgery in 4 patients with either complete procidentia or vaginal vault eversion. The procedure involves a modification of the bilateral sacrospinous vaginal vault fixation using two additional sutures to suspend the sigmoid colon from the sacrospinous ligament. Clinical and functional results have been excellent. This is the first description of a vaginal approach to the repair of a sigmoidocele.

Sexuality after hysterectomy.

OBJECTIVE: The availability of alternative therapies for abnormal gynecologic bleeding has prompted a reexamination of the impact of total hysterectomy on a woman's quality of life. This paper examines the evidence about the impact of hysterectomy on one aspect of quality of life, sexuality. DATA SOURCES: A systematic review of the English and German language literature was conducted using the search terms "sexuality," "hysterectomy," "libido," "orgasm," and "outcomes." Additional papers found in the bibliographies of theses papers were reviewed. METHODS OF STUDY SELECTION: Eighteen studies were found, eight prospective and ten retrospective. With a few exceptions, the methodologic quality of the studies was poor, but we opted to review all of the studies given the paucity of data on this important subject. TABULATION, INTEGRATION, AND RESULTS: The studies were evaluated for methodologic quality using a scoring system described in the paper and for their findings concerning the impact of hysterectomy on sexuality. chi(2) and Fischer exact test were used to analyze nominal variables. Outcome measures were usually not validated and most studies did not consider important confounding factors. Most studies in this review showed either no change or an enhancement of sexuality in women who had a hysterectomy. CONCLUSION: The majority of research evaluating the effect of hysterectomy on sexuality was poorly designed. The available evidence shows that quality of life is improved for most women who had hysterectomy and that hysterectomy did not adversely affect sexuality. A number of confounding factors with the potential to have either a positive or negative impact on sexuality, independent of hysterectomy, should be taken into account in future studies.

Club foot, an adverse outcome of early amniocentesis: disruption or deformation? CEMAT. Canadian Early and Mid-Trimester Amniocentesis Trial.

An association between the occurrence of club foot and early amniocentesis has been reported. The largest of these randomised studies was the Canadian Early and Mid-Trimester Amniocentesis Trial. Data describing the neonatal outcome, focusing on this association, are presented. Possible mechanisms for the association and the implications for the development of club foot are discussed.

Uterine fluid irrigation and absorption in hysteroscopic endometrial ablation.

OBJECTIVE: To compare two techniques of irrigation flow control with regard to risk of absorption of uterine irrigation fluid during operative hysteroscopy. METHODS: We compared two techniques of uterine irrigation fluid outflow management-passive gravity outflow and direct connection of the outflow to wall suction-in a randomized controlled trial involving 40 women undergoing hysteroscopic endometrial ablation. The amount of fluid absorbed by each subject was calculated, as were operating time, uterine size, and endometrial pharmacologic preparation. Endometrial thickness and operator view were graded visually by the surgeon. RESULTS: The median (range) amount of irrigation fluid absorbed was 450 mL (0-2300) in the group in which passive gravity outflow was used and 0 mL (700 mL excess outflow to 300 mL absorption) in the group in which direct connection of the outflow to wall suction was used (P < .001). None of the other variables that might have influenced uterine irrigation fluid absorption (operating time, uterine size, pharmacologic endometrial preparation, or endometrial thickness) differed between the two groups. CONCLUSION: Connecting the outflow of the uterine irrigation system to wall suction is a simple and effective method of reducing the risk of fluid absorption during endometrial ablation.

Application of the concept of 'therapeutic index' to surgery for stress incontinence.

The pharmacologic concept of therapeutic index can be applied to surgery for stress incontinence to obtain an objective prediction of surgical outcome. The rationale and mechanics of its application to surgery are discussed in this article. The conclusions support current clinical trends which favor discarding the anterior repair and needle suspension procedures as first-line surgical treatment of stress urinary incontinence in favor of the retropubic procedures. Suburethral sling procedures should be, as now, reserved for second-line surgical treatment of stress urinary incontinence.