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.

Balanced reciprocal translocation mosaicism: new cases and a literature review.

Mosaicism for a balanced reciprocal translocation is uncommon. These two new cases were detected during investigation of infertility and miscarriages. Otherwise, the probands were normal. Of five previously described cases, only one was possibly syndromal. More reports of this class of chromosomal aberration are needed to assess accurately the risk of phenotypic abnormalities.

Microphthalmia, marked short stature, hearing loss, and developmental delay: extension of the phenotype of GOMBO syndrome?

An adult male with microphthalmia, severe developmental delay, conductive hearing loss, marked short stature of prenatal onset, and radiographic skeletal changes is described. A review of the literature, focusing on his major findings, suggests that his manifestations might be an extension of the phenotype of GOMBO (growth retardation, ocular abnormalities, microcephaly, brachydactyly, oligophrenia) syndrome.

Weaver syndrome with pes cavus.

Few cases have been described of the Weaver syndrome, an overgrowth syndrome with advanced skeletal age. Here we report bilateral pes cavus in an affected girl.

Balanced nonacrocentric whole-arm reciprocal translocations: a de novo case and literature review.

We report a new de novo case of a balanced whole-arm reciprocal translocation, detected at prenatal diagnosis for late maternal age. A review of previous cases indicates there is a risk of chromosomally abnormal liveborn offspring when a parent is a carrier of this type of translocation, particularly when the translocated region is a small chromosomal segment. Due to the limited number of cases, exact reproductive risks are not available. This is the second example of such a translocation of chromosomes 1 and 5, raising the possibility of nonrandom involvement of certain chromosomes in balanced nonacrocentric whole-arm reciprocal translocations.

Neonatal manifestations of Schwartz-Jampel syndrome.

Schwartz-Jampel syndrome generally presents in childhood with short stature, limited joint mobility, masklike facies with blepharophimosis, myotonia, and often muscle hypertrophy. Few cases with neonatal manifestations have been described. A newborn with severe manifestations is reported and the literature is reviewed.

Adams-Oliver syndrome: a case with juvenile chronic myelogenous leukemia and chylothorax.

We report on a patient with Adams-Oliver syndrome and report new findings: a chylous pleural effusion and juvenile chronic myelogenous leukemia. Also, our patient had congenital heart disease, confirming that heart lesions are a manifestation in this syndrome. The major manifestations of this disorder are summarized. Included are cases not previously recognized as having Adams-Oliver syndrome identified in a literature survey. Distal limb deficiency is commonest with more frequent and more severe involvement of the lower limbs. Scalp defects are the second commonest manifestation, while an underlying skull defect is not infrequent. Cutis marmorata telangiectatica and dilated scalp veins are significant signs of this condition. This review highlights unresolved questions about Adams-Oliver syndrome.

Moving satellites and unstable chromosome translocations: clinical and cytogenetic implications.

We describe 2 families in which acrocentric short arm material moved from one chromosome to another. In case 1, a meiotic event resulted in movement of an unusually large paternal 21p to chromosome 13 in the fetus. In case 2, a mitotic event resulted in fetal mosaicism. The short arm material from a paternal chromosome 15 moved to chromosome 14 in some of the fetal cells. Movement of acrocentric short arm material resulted from breakage and exchange in centromeric areas of repetitive DNA. We suggest the mechanism may be similar to that of previously reported "jumping" translocations. Failure to recognize movement of the short arms of acrocentric chromosomes can result in erroneous interpretation of prenatal cytogenetic results and of other cytogenetic assays dependent on acrocentric short arm polymorphisms.

Infantile lethal variant of Simpson-Golabi-Behmel syndrome associated with hydrops fetalis.

Simpson-Golabi Behmel syndrome (SGBS) is an X-linked disorder characterized by pre- and postnatal macrosomia, minor facial anomalies, and variable visceral, skeletal, and neurological abnormalities. Since its first description by Simpson et al. [1975: BD:OA XI(2):18-24], a wide clinical range of cases has been reported. There is great variability in severity, ranging from a mild form associated with long-term survival to an early lethal form with multiple congenital anomalies and severe mental retardation. In 8 reported families, affected individuals died in infancy. Here we present 4 maternally related, male cousins with a severe variant of SGBS. One of these males was aborted therapeutically at 19 weeks of gestation following the detection of multicystic kidneys on ultrasound. The 3 liveborn males were hydropic at birth with a combination of craniofacial anomalies including macrocephaly; apparently low-set, posteriorly angulated ears; hypertelorism; short, broad nose with anteverted nares; large mouth with thin upper vermilion border; prominent philtrum; high-arched or cleft palate; short neck; redundant skin; hypoplastic nails; skeletal defects involving upper and lower limbs; gastrointestinal and genitourinary anomalies. All 3 patients were hypotonic and neurologically impaired from birth. With the exception of a trilobate left lung in one patient, the cardiorespiratory system was structurally normal. All patients died within the first 8 weeks of life of multiple complications including pneumonia and sepsis. Two SGBS kindreds, with moderate expression of the condition, have been mapped to Xq27. It is not known whether severe, familial cases, such as ours, are genetically distinct from and map to another locus. Final resolution of the genetic basis of the phenotypic variability in SGBS must await cloning and mutation analysis of the SGBS gene(s).

Abdominal distension in Kaufman-McKusick syndrome.

A female infant with Kaufman-McKusick syndrome redeveloped respiratory distress and abdominal distention at 5 weeks of age. Ultrasonography demonstrated recurrence of peritoneal cysts and hydrometrocolpos. It is postulated that refluxing vaginal secretions may contribute to the abdominal distention seen in many infants with Kaufman-McKusick syndrome.

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.

Prenatal diagnosis of retinal detachment in Walker-Warburg syndrome.

Lissencephaly, hydrocephalus, and eye abnormalities characterize patients with the Walker-Warburg syndrome, an uncommon autosomal recessive condition. Encephaloceles occur in about 50% of patients. We describe the prenatal diagnosis of this condition based on the ultrasonographic findings of retinal detachment, hydrocephalus, and an encephalocele in a fetus not known to be at risk.

In utero fetal muscle biopsy for the diagnosis of Duchenne muscular dystrophy in a female fetus "suddenly at risk".

DNA methods to diagnose Duchenne muscular dystrophy (DMD) are not always informative, and we have published previously the first instance of in utero muscle biopsy to assess dystrophin in a male fetus having the same "X" as an affected sib. We present here a female fetus with a de novo X,1 translocation with breakpoint at Xp21, detected on amniocentesis for advanced maternal age. The translocation breakpoint placed her at high risk for DMD. In utero muscle biopsy at 20 weeks of gestation produced a specimen positive for dystrophin immunofluorescence indicating a likely normal fetus. The pregnancy was continued, and at term the baby girl was found to have normal serum creatine kinase levels, and was therefore unaffected with DMD. Our experiences add de novo Xp21 translocation to the indications for in utero muscle biopsy for diagnosis of DMD.

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.

Currycombs for the vaginal paravaginal defect repair.

BACKGROUND: The paravaginal defect, present in more than three-quarters of patients with cystoceles, can be repaired by both the abdominal and vaginal approaches. The technical challenges of the vaginal paravaginal repair have militated against its widespread adoption by gynecologic surgeons. INSTRUMENT: Currycombs can be used to facilitate suture management during vaginal paravaginal repair. EXPERIENCE: The vaginal paravaginal repair using currycombs was performed as part of pelvic repair surgery on 27 patients. Perioperative complications were minimal. A cystocele cure rate of 80% was achieved after a mean follow-up of 8 months. CONCLUSION: The use of currycombs during performance of the vaginal paravaginal repair facilitates suture management. The addition of this technique should help gynecologic surgeons to perform this somewhat daunting surgical procedure.

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.

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.

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.

A simplified protocol for pessary management.

OBJECTIVE: To evaluate a simplified protocol for pessary management. METHODS: Women with symptomatic pelvic organ prolapse who opted for pessaries were enrolled in a prospective simplified protocol for pessary management. After the initial pessary fitting, they were seen at 2 weeks for reexamination and thereafter at 3- to 6-month intervals. RESULTS: One hundred ten women (mean age 65 years) were enrolled, and 81 (74%) of them were fitted successfully with a pessary. Life-table analysis showed that 66% of those who used a pessary for more than 1 month were still users after 12 months and 53% were still users after 36 months. The severity of pelvic prolapse did not predict the likelihood of pessary failure except in cases of complete vaginal eversion. Patients complaining of stress incontinence were less likely to have a successful pessary fitting and more likely to opt for surgery. Current hormone use and substantial perineal support do not predict greater likelihood of pessary fitting success. No serious complications from using the pessary were observed in the study sample. CONCLUSION: Stringent guidelines calling for frequent pelvic examinations during pessary use can be relaxed safely. Pessaries can be offered as a safe long-term option for the management of pelvic prolapse.

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.