Cervical elastography using E-Cervix™ for prediction of preterm birth in twin pregnancies with threatened preterm labor.

OBJECTIVE: To evaluate the prediction performance of E-Cervix™ for preterm birth in twin pregnancies with threatened preterm labor. METHODS: This was a single-center retrospective cohort study of twin pregnancies presenting to obstetrics triage for threatened preterm labor (PTL) between 23 0/7 - 33 6/7 weeks who received screening for PTL with transvaginal ultrasound cervical length (TVU CL) and cervical elastography with E-Cervix™ at the time of triage. Cervical elastography parameters were examined and compared between women who delivered preterm and those who did not. The quantification of cervical strain was calculated by a data analysis system that directly analyzes raw data from the region of interest (ROI) and described as hardness ratio (HR), mean strain level within 1 cm from internal (IOS) and external (EOS) os. RESULTS: 63 twin gestations without prior preterm birth and with threatened PTL between 23 0/7 - 33 6/7 weeks of gestation were included in the study. 27 (42.9 %) had cervical length < 25 mm, and were admitted for true PLT. Out of the 36 women with cervical length ≥ 25 mm, 6 (16.7 %) were admitted. Women with threatened PTL had significantly higher HR compared to those with true PTL (p < 0.01), and significantly lower IOS and EOS. Women who delivered preterm had significantly higher HR compared to those who did not delivery preterm and significantly lower IOS and EOS, in overall cohort, and in the subset of women with true PTL. Incidences of HR < 50 % and < 35 % were statistically significantly higher in women who delivered preterm compared to those who did not (p < 0.01). CONCLUSION: Cervical elastography with E-Cervix™ may be useful for assessment of twin gestations presenting to obstetrics triage for threatened PTL.

The microstructure of intra- and interpersonal coordination.

Movements are naturally composed of submovements, i.e. recurrent speed pulses (2-3 Hz), possibly reflecting intermittent feedback-based motor adjustments. In visuomotor (unimanual) synchronization tasks, partners alternate submovements over time, indicating mutual coregulation. However, it is unclear whether submovement coordination is organized differently between and within individuals. Indeed, different types of information may be variably exploited for intrapersonal and interpersonal coordination. Participants performed a series of bimanual tasks alone or in pairs, with or without visual feedback (solo task only). We analysed the relative timing of submovements between their own hands or between their own hands and those of their partner. Distinct coordinative structures emerged at the submovement level depending on the relevance of visual feedback. Specifically, the relative timing of submovements (between partners/effectors) shifts from alternation to simultaneity and a mixture of both when coordination is achieved using vision (interpersonal), proprioception/efference-copy only (intrapersonal, without vision) or all information sources (intrapersonal, with vision), respectively. These results suggest that submovement coordination represents a behavioural proxy for the adaptive weighting of different sources of information within action-perception loops. In sum, the microstructure of movement reveals common principles governing the dynamics of sensorimotor control to achieve both intra- and interpersonal coordination.

Placental DNA methylation profile as predicting marker for autism spectrum disorder (ASD).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impairs normal brain development and socio-cognitive abilities. The pathogenesis of this condition points out the involvement of genetic and environmental factors during in-utero life. Placenta, as an interface tissue between mother and fetus, provides developing fetus requirements and exposes it to maternal environment as well. Therefore, the alteration of DNA methylation as epigenetic consequence of gene-environmental interaction in the placenta could shed light on ASD pathogenesis. In this study, we reviewed the current findings on placental methylation status and its association with ASD. Differentially methylated regions (DMRs) in ASD-developing placenta were found to be mainly enriched in ASD gene loci affecting synaptogenesis, microtubule dynamics, neurogenesis and neuritogenesis. In addition, non-genic DMRs in ASD-placenta proposes an alternative contributing mechanism for ASD development. Our study highlights the importance of placental DNA methylation signature as a biomarker for ASD prediction.

Interpersonal synchronization of movement intermittency.

Most animal species group together and coordinate their behavior in quite sophisticated manners for mating, hunting, or defense purposes. In humans, coordination at a macroscopic level (the pacing of movements) is evident both in daily life (e.g., walking) and skilled (e.g., music and dance) behaviors. By examining the fine structure of movement, we here show that interpersonal coordination is established also at a microscopic - submovement - level. Natural movements appear as marked by recurrent (2-3 Hz) speed breaks, i.e., submovements, that are traditionally considered the result of intermittency in (visuo)motor feedback-based control. In a series of interpersonal coordination tasks, we show that submovements produced by interacting partners are not independent but alternate tightly over time, reflecting online mutual adaptation. These findings unveil a potential core mechanism for behavioral coordination that is based on between-persons synchronization of the intrinsic dynamics of action-perception cycles.

Cervical elastography using E-cervix for prediction of preterm birth in singleton pregnancies with threatened preterm labor.

OBJECTIVE: E-Cervix™ (WS80A; Samsung, Seoul, Korea) elastography is a recent quantification tool to measure the stiffness of the cervix using strain elastography. The aim of this study was to evaluate the prediction performance of E-cervix for preterm birth in singleton gestation with threatened preterm labor (PTL). METHODS: This was a cohort study of singleton pregnancies without prior preterm birth presenting to obstetrics triage for threatened PTL between 23 0/7 and 33 6/7 week who received screening for PTL with transvaginal ultrasound cervical length (TVU CL) and cervical elastography with E-cervix at the time of triage. Cervical elastography parameters were examined and compared between women who delivered preterm and those who did not. The quantification of cervical strain was calculated by a data analysis system that directly analyses raw data from the region of interest (ROI) and described as hardness ratio (HR), mean strain level within 1 cm from internal os (IOS) and external os (EOS). RESULTS: Ninety-five singleton pregnancies without prior preterm birth and with threatened PTL between 23 0/7 and 33 6/7 week of gestation were included in the study. Forty-two (44.2%) had cervical length <25 mm, and were admitted for true PLT. Out of the 53 women with cervical length ≥25 mm, 40 (75.5%) were discharged, and 13 (24.5%) were admitted. Women with threatened PTL but without true PTL, had significantly higher HR compared to those with true PTL (49.0 ± 20.9% versus 34.8 ± 19.6%; p < .01), and significantly lower stiffness of cervical IOS and EOS. Women who delivered preterm had significantly lower HR compared to those who did not delivery preterm, in overall cohort, and in the subset of only women with true PTL. Incidences of HR < 50% and <35% were statistically significantly higher in women who delivered preterm compared to those who did not (p < .01). CONCLUSIONS: Cervical elastography with E-cervix may be useful for the assessment of women presenting to obstetrics triage for threatened PTL. Women with low HR, especially with HR less than 50 or 35%, are at increased risk of PTB. CONDENSATION: Women who delivered preterm had significantly lower HR compared to those who did not delivery preterm and significantly lower IOS and EOS, in overall cohort, and in the subset of women with true PTL. Incidences of HR < 50% and <35% were statistically significantly higher in women who delivered preterm compared to those who did not (p < .01). KEY MESSAGE: Cervical elastography with E-cervix may be useful for the assessment of women presenting to obstetrics triage for threatened PTL.

Vaginal lactoferrin in prevention of preterm birth in women with bacterial vaginosis.

OBJECTIVE: To evaluate use of vaginal lactoferrin in prevention of preterm birth (PTB) in women with first trimester bacterial vaginosis and prior spontaneous PTB. METHODS: This is a retrospective cohort study of all consecutive singleton gestations with prior PTB, and first trimester diagnosis of bacterial vaginosis. Women who were found to have bacterial vaginosis were recommended lactoferrin 300 mg vaginal tablets daily for 21 days. The primary outcome was the incidence of PTB at less than 37 weeks of gestations. Outcomes were compared in women who received daily lactoferrin with those who did not. RESULTS: During the study period, 847 pregnant women with prior spontaneous PTB were screened for bacterial vaginosis. Of them, 193 were found to have bacterial vaginosis in the first trimester, with an overall incidence of 22.8%. Out of the 193 women, 125 met the inclusion criteria for the study and were analyzed. Sixty of the included women received vaginal lactoferrin, while 65 did not. Women who received supplementation with lactoferrin had a significantly lower rate of PTB < 37 weeks (25.0 versus 44.6%; p = .02), lower mean gestational age at delivery (37.7 ± 3.2 versus 35.9 ± 4.1 weeks; p = .01), and lower rate of admission for threatened PTL (45.0 versus 70.8%; p = .04). No between-group differences were noticed in the other outcomes, including chorioamnionitis, PPROM < 34 weeks, and neonatal outcomes. No cases of late miscarriage were reported in our cohort. No cases of adverse events were reported. CONCLUSION: Based on this small single-center retrospective study, supplementation with vaginal lactoferrin in women with first trimester bacterial vaginosis may be an option to reduce the risk of preterm delivery.

"HEALTH-FOR": a pilot study to assess eating habits during pregnancy among Arab and Chinese immigrants living in Italy.

A 1-year pilot cross-sectional study was performed to assess eating behaviours and lifestyle among Chinese and Arab pregnant immigrants to Italy. A number of 95 Chinese and 83 Arab women were interviewed. Two ethnic-specific food frequency questionnaires were designed to reflect the habitual diet of women belonging to these ethnic groups. Food items frequency of consumption was discussed using healthy eating guidelines. In both populations, women met healthy eating guidelines, except for salt intake, which was double than recommended; meat, sweet products and sugar-sweetened beverages were consumed more frequently than recommended, while olive oil and yogurt were eaten less frequently. Chinese women did not reach the recommendations for dairy products and fatty fish and exceeded those for red and processed meat, whereas Arab women exceeded the recommendations for cheese. Our findings suggest that the Italian food environment did not significantly affect Chinese and Arab pregnant immigrants' diet.

DSM-5 Alternative Model of Personality Disorder Dysfunctional Personality Traits as Predictors of Self-Reported Aggression in an Italian Sample of Consecutively Admitted, Personality-Disordered Psychotherapy Patients.

In order to assess the relationships between DSM-5 Alternative Model of Personality Disorder (AMPD) maladaptive personality traits and self-reports of aggression, 508 Italian adult participants who met at least one DSM-IV Axis II/DSM-5 Section II personality disorder (PD) diagnosis were administered the Personality Inventory for DSM-5 (PID-5) and the Aggression Questionnaire (AQ). Analysis results showed that multiple regression results, PID-5 Hostility, Callousness, and Risk Taking trait scale scores explained a large amount of variance in AQ Physical Aggression (PA) scores. Moreover, PID-5 Hostility, Callousness, and Risk Taking explained more than 20% of the variance in the AQ Physical Aggression scale scores that was left unexplained by selected continuously scored DSM-IV Axis II/DSM-5 Section II PDs, whereas SCID-II Paranoid, Narcissistic, Borderline, and Antisocial PDs added only 4% of variance to the amount of variance in AQ Physical Aggression scores that was already explained by the PID-5 trait scale scores.

Fractional microablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of nonestrogenic local treatments: a retrospective study.

OBJECTIVE: Vulvovaginal atrophy (VVA) is a condition frequently observed in menopause. Its symptoms can significantly affect the quality of life of patients. Since VVA is related to estrogen deficiency, chemotherapy and hormone therapy for breast cancer (BC) might cause VVA by inducing menopause. Given the lack of effective treatment for VVA in BC survivors, we retrospectively evaluated the efficacy and tolerability of fractional microablative CO2 laser therapy in these patients. METHODS: We treated 82 BC survivors with three cycles of CO2 laser after failure of topical nonestrogenic therapy. The severity of symptoms was assessed with a visual analog scale (VAS) at baseline and after completion of laser therapy. Differences in mean VAS scores of each symptom before and after treatment were assessed with multiple t tests for pairwise comparisons. Multivariate analyses were used to adjust the final mean scores for the main confounding factors. RESULTS: Pre versus post-treatment differences in mean VAS scores were significant for sensitivity during sexual intercourse, vaginal dryness, itching/stinging, dyspareunia and dysuria (P < 0.001 for all), bleeding (P = 0.001), probe insertion (P = 0.001), and movement-related pain (P = 0.011). Multivariate analyses confirmed that results were significant, irrespective of patients' age and type of adjuvant therapy. CONCLUSION: This study shows that CO2 laser treatment is effective and safe in BC patients with iatrogenic menopause. However, the optimal number of cycles to administer and the need for retreatment remain to be defined. Prospective trials are needed to compare CO2 laser therapy with therapeutic alternatives.

Fractional microablative CO2 laser for vulvovaginal atrophy in women treated with chemotherapy and/or hormonal therapy for breast cancer: a retrospective study.

OBJECTIVES: Breast cancer is one of the most common malignancies in women. Hormonal treatment and chemotherapy induce a transient or permanent menopause status. Vulvovaginal atrophy (VVA) is a frequent debilitating symptom of menopause that is best treated with local or systemic estrogen formulations. Because estrogens drive the growth of the majority of breast cancers, most effective VVA therapies are precluded. The aim of this study was to evaluate the effects of fractional microablative CO2 laser on sexual function and in relieving symptoms in women with breast cancer and VVA induced or exacerbated by iatrogenic menopause. METHODS: This retrospective study included 26 women affected by hormone-receptor positive breast tumors and treated for VVA symptoms with the fractional microablative CO2 laser system. Every 30 to 40 days, women underwent a cycle of treatment for a total of three cycles. During each cycle, women underwent a gynecological examination and completed visual analog scale questionnaires designed to assess (1) the degree of symptoms and (2) procedure-related discomfort. RESULTS: Treatment resulted in a significant regression of VVA symptoms and procedure-related discomfort versus baseline (P < 0.001 in almost all cases). No adverse reactions were observed nor reported by women. CONCLUSIONS: Fractional microablative CO2 laser treatment is associated with a significant improvement of VVA symptoms in women affected by hormone-driven breast cancer. This procedure has the advantage of relieving iatrogenic/physiological VVA symptoms without resorting to contraindicated estrogen preparations, which have been the most effective therapy thus far.

5D CNS+ Software for Automatically Imaging Axial, Sagittal, and Coronal Planes of Normal and Abnormal Second-Trimester Fetal Brains.

The purpose of this study was to test new 5D CNS+ software (Samsung Medison Co, Ltd, Seoul, Korea), which is designed to image axial, sagittal, and coronal planes of the fetal brain from volumes obtained by 3-dimensional sonography. The study consisted of 2 different steps. First in a prospective study, 3-dimensional fetal brain volumes were acquired in 183 normal consecutive singleton pregnancies undergoing routine sonographic examinations at 18 to 24 weeks' gestation. The 5D CNS+ software was applied, and the percentage of adequate visualization of brain diagnostic planes was evaluated by 2 independent observers. In the second step, the software was also tested in 22 fetuses with cerebral anomalies. In 180 of 183 fetuses (98.4%), 5D CNS+ successfully reconstructed all of the diagnostic planes. Using the software on healthy fetuses, the observers acknowledged the presence of diagnostic images with visualization rates ranging from 97.7% to 99.4% for axial planes, 94.4% to 97.7% for sagittal planes, and 92.2% to 97.2% for coronal planes. The Cohen κ coefficient was analyzed to evaluate the agreement rates between the observers and resulted in values of 0.96 or greater for axial planes, 0.90 or greater for sagittal planes, and 0.89 or greater for coronal planes. All 22 fetuses with brain anomalies were identified among a series that also included healthy fetuses, and in 21 of the 22 cases, a correct diagnosis was made. 5D CNS+ was efficient in successfully imaging standard axial, sagittal, and coronal planes of the fetal brain. This approach may simplify the examination of the fetal central nervous system and reduce operator dependency.

Accuracy of Hysteroscopic Metroplasty With the Combination of Presurgical 3-Dimensional Ultrasonography and a Novel Graduated Intrauterine Palpator: A Randomized Controlled Trial.

UNLABELLED: STUDY OBJECTIVE: To assess whether the use of a novel graduated intrauterine palpator can improve the accuracy of hysteroscopic metroplasty, introducing objective intraoperative criteria. DESIGN: A prospective randomized study (Canadian Task Force I, evidence obtained from a properly design, randomized, controlled trial). SETTING: University Federico II hysteroscopic clinic. PATIENTS: Ninety women with a uterine septum diagnosed during office hysteroscopy and 3-dimesional transvaginal ultrasound (3D-TVS) were randomized into 2 groups: group T (metroplasty with intrauterine palpator) (n = 45) and group C (metroplasty without intrauterine palpator) (n = 45). INTERVENTIONS: Outpatient hysteroscopic metroplasty under conscious sedation using a 5-mm hysteroscope and miniaturized 5F instruments including a bipolar electrode for the removal of three quarters of the septum, blunt scissors to refine the base of the septum, and an intrauterine palpator to measure the portion of the removed septum (only group T). 3D-TVS and second-look hysteroscopy were used to identify the number of optimal (residual septum <5 mm), suboptimal (residual septum 5-10 mm), and incomplete resections (residual septum >10 mm). In group T, metroplasty was stopped when the intrauterine palpator showed that the resected septum corresponded to presurgical ultrasonographic measurements in order to obtain a fundal notch of 1.0 cm. In group C, metroplasty was interrupted once the tubal ostia were clearly visible on the same line and/or hemorrhage from small myometrial vessels of the fundus was observed. MEASUREMENTS AND MAIN RESULTS: No differences were observed in baseline characteristics between the 2 groups. The proportion of patients with complete septum resection was significantly higher in group T (71.5% vs 41%, χ(2): p = .006; relative risk: 1.684; 95% confidence interval, 1.116-2.506). Suboptimal resection was achieved in 13 cases (28.5%) in group T and 14 cases (20%) in group C, whereas incomplete resection was observed in only 12 patients in group C (27%). CONCLUSION: Presurgical evaluation with 3D-TVS together with the use of a graduate intrauterine palpator improves the accuracy of hysteroscopic metroplasty, allowing complete removal of a uterine septum in 1 surgical step.

An Exceptional Case of Complete Septate Uterus With Unilateral Cervical Aplasia (Class U2bC3V0/ESHRE/ESGE Classification) and Isolated Mullerian Remnants: Combined Hysteroscopic and Laparoscopic Treatment.

STUDY OBJECTIVE: To report the combined hysteroscopic and laparoscopic treatment of a complete septate uterus with unilateral cervical aplasia (class U2bC3V0/ESHRE/ESGE classification) and isolated mullerian remnants. DESIGN: Step-by-step presentation of the surgical treatment (Canadian Task Force classification 4). SETTING: Complete septate uterus with unilateral cervical aplasia (formally Robert's uterus) is characterized by the presence of a uterine septum completely dividing the endometrial cavity into an obstructed hemicavity and a contralateral nonobstructing hemicavity connected normally to the existing cervix. It has always been described as isolated without any associated anomaly. PATIENT: A 30-year-old woman was referred to our department for dysmenorrhea and primary infertility. Hysterosalpingography showed the presence of a right (RT) hemiuterus with a patent fallopian tube; further evaluation with 2- and 3-dimensional ultrasound and magnetic resonance imaging showed an externally normal-appearing uterus, a right normal hemicavity connected normally with the existed cervix and, a left hemicavity fully divided from the right one by a complete septum and not connected with the cervix. Interestingly, a peculiar complex mass with cystic areas, attached posterolaterally from the left side to the uterine wall at the level of the isthmus and the upper cervix, was also diagnosed. INTERVENTIONS: The study protocol was approved by our local institutional review board. During outpatient hysteroscopy, a right uterine hemicavity with a single ostium was identified without any communication with the left hemicavity. The patient was then scheduled for combined laparoscopic and hysteroscopic treatment. During laparoscopy, a normal uterine body with multiple myomas and a pseudocystic lesion attached posteriorly and left laterally to the uterus at the level of the isthmus and the upper cervix were shown; no communication between the cystic part of that lesion and the isthmus or the cervicovaginal canal was observed. During hysteroscopy, a longitudinal incision of the septum with a 5F bipolar electrode was performed; the left hemicavity was opened, and the corresponding tubal ostium was identified. The pseudocystic lesion was then excised after opening and sent for pathological analysis; the defect was closed with interrupted intracorporeal knots. MEASUREMENTS AND MAIN RESULTS: A single normal endometrial cavity with both tubal ostia was obtained, thus restoring obstruction by unification of the uterine cavity. A histologic report of the removed pseudocystic lesion was compatible with the diagnosis of mullerian remnants. A follow-up hysteroscopy 3 months after showed a normal uterine cavity without postsurgical adhesions. CONCLUSION: The use of 3-dimensional ultrasound and magnetic resonance imaging in combination with the new ESHRE/ESGE classification system gives the opportunity to obtain a precise representation of the female genital anatomy even in the presence of complex anomalies. Although a septate uterus with unilateral cervical aplasia has been already described, the presence of mullerian remnants is a rare entity associated with cyclic pelvic pain, thus needing adequate recognition and treatment. The combined hysteroscopic and laparoscopic approach offers a unique opportunity for the treatment of complex anomalies.

Differentiating between septate and bicornuate uterus: bi-dimensional and 3-dimensional power Doppler findings.

STUDY OBJECTIVE: To assess if any difference could be found in uterine vascularization between septate and bicornuate uterus. DESIGN: Pilot study (Canadian Task Force classification II-2). SETTING: University hospital infertility clinic. PATIENTS: One hundred nine women with complete duplication of the uterine cavity. All had already received the final diagnosis of the type of uterine malformation, either septate uterus or bicornuate uterus, via diagnostic hysteroscopy and laparoscopy. Another group of 10 patients with uterine anomalies and affected by ovarian mass were also evaluated via intravenous contrast medium-enhanced ultrasound examination. INTERVENTIONS: Patients were evaluated using 2-dimensional and 3-dimensional power Doppler imaging of the uterus. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients with septate uterus, with or without cervical and vaginal duplication, and 36 patients with bicornuate uterus were selected for inclusion in the study. Irregular vascular networks were detected between the 2 hemicavities in the patients with septate uterus. All bicornuate uteri showed a peculiar vascular network between the 2 hemicavities: the main recognizable vessels formed a network depicting the Greek letter γ at the level of the uterine midline. Detection of the γ sign can be used to differentiate septate from bicornuate uterus. This finding was also confirmed in patients who underwent intravenous contrast medium-enhanced ultrasound examination. CONCLUSIONS: power Doppler provides a new and uninvasive tool for differentiation of septate from bicornuate uterus.

Cystic variant of endometrial stromal sarcoma: report of two cases.

Endometrial stromal sarcoma is an uncommon tumor representing 0.2% of all uterine neoplasm and 15% to 26% of uterine sarcomas. Endometrial stromal sarcoma has a gross appearance as single nodule, multiple masses, or a poorly demarcated lesion with occasional cystic degeneration; rarely, it shows a cystic multilocular feature. We report 2 cases of endometrial stromal sarcoma with a prominent cystic appearance, forming multilocular cystic mass, detected by ultrasonography. The differential diagnosis among multicystic endometrial stromal sarcoma and cystic uterine tumors might be very difficult.

Combined hysteroscopic findings and 3-dimensional reconstructed coronal view of the uterus to avoid laparoscopic assessment for inpatient hysteroscopic metroplasty: pilot study.

STUDY OBJECTIVE: To assess the use of 3-dimensional (3D) reconstructed coronal view of the uterus and intraoperative hysteroscopic findings to avoid diagnostic laparoscopy during inpatient hysteroscopic metroplasty. DESIGN: Pilot study (Canadian Task Force classification II). SETTING: University hospital infertility clinic. PATIENTS: Fifty-nine patients with recurrent abortion and double uterine cavity with 3D sonographic diagnosis of septate uterus undergoing inpatient hysteroscopic metroplasty. INTERVENTIONS: Inpatient hysteroscopic treatment of septate uterus without laparoscopic diagnosis. In addition to sonographic observations, 2 intraoperative hysteroscopic criteria were used to confirm the diagnosis: visualization of muscular fibers and myometrial blood vessels. MEASUREMENTS AND MAIN RESULTS: Operative parameters (operative time and fluid absorption), complications (incomplete resection and uterine perforation), requirement for a second intervention, and shape of the uterine cavity at hysteroscopic follow-up. In 56 of 59 patients (94.9%), intervention was performed without complications, and in 3 cases, intervention was suspended because of intraoperative suspicion of bicornate uterus. These 3 patients underwent laparoscopy, which confirmed the diagnosis of septate uterus. In all cases, incision was considered sufficient. Postoperative diagnostic hysteroscopy in all patients showed a normal cavity (fundal notch <1 cm). CONCLUSIONS: Combined use of hysteroscopic confirming criteria and 3D sonography seems to be a reliable and simple strategy for characterizing the presence of septate uterus and to perform inpatient metroplasty usually without laparoscopic visualization of the uterine fundus.

Prenatal ultrasound diagnosis of a case of Pfeiffer syndrome without cloverleaf skull and review of the literature.

Pfeiffer syndrome is characterized by bilateral coronal craniosynostosis, midface hypoplasia, beaked nasal tip, broad and medially deviated thumbs and great toes. Originally, it was described in eight persons from three generations in a pedigree consistent with an autosomal dominant transmission. Since then, several reports have documented its high clinical and genetic heterogeneity. The condition is usually detected in the newborn period or later, and very few prenatal ultrasound diagnoses have been reported. We present a case of Pfeiffer syndrome prenatally diagnosed at 20 weeks' gestation, in which the sonographic features of craniosynostosis, hypertelorism associated with an extreme proptosis, and broad thumb led to the diagnosis, confirmed after termination of pregnancy by dysmorphological, pathological and radiological evaluation. DNA analysis of the fibroblast growth factor receptor 2 (FGFR2) showed a missense mutation consisting in a transversion G --> C at nucleotide 870. This led to a Trp290Cys amino acidic substitution. We discuss the relevant findings of our and previously published cases. Our report demonstrates that a careful sonographic examination can lead to an early prenatal diagnosis of Pfeiffer syndrome also in cases without cloverleaf skull.