Novel neurofibromatosis type 2 mutation presenting with status epilepticus.

Neurofibromatosis type 2 (NF2) is a dominantly inherited syndrome caused by mutations of the tumour-suppressor NF2, which encodes the merlin protein. Mutations are associated with a predisposition to development of benign tumours in the central nervous system. Even though cerebral cortical lesions are frequently associated with seizures, epilepsy is rarely described in NF2. Here, we describe an adult case of NF2 in which the onset of symptoms was characterised by status epilepticus. In this patient, we identified the novel c.428_430delCTTdel mutation in NF2, involving the amino-terminal FERM domain, which is fundamental for the correct tumour suppressor function of the protein. Bioinformatic analyses revealed an important structural perturbation of the FERM domain, with a predicted impairment of the anti-tumour activity.

Fibroids-related complications in pregnancy: a twelve-year long experience at a maternal-fetal medicine referral center.

BACKGROUND: Uterine fibroids are the most frequent female benign tumor, which can cause complications during pregnancy, mainly pain. Differential diagnosis may be challenging and a standardized management approach is lacking. We aim to propose an algorithm for the differential diagnosis of pain during pregnancy and for management of fibroid-related pain. METHODS: A retrospective cohort study of all pregnant women admitted to our center for complications related to fibroids between 2008 and 2019. Data regarding clinical examination, laboratory results, imaging parameters, as well as perinatal outcomes, were collected and assessed (Fisher's Exact Test). RESULTS: Twenty-four pregnant patients were admitted for fibroid-related complications. Six patients were admitted more than one times, for a total of 34 admissions. The main cause of hospital admission was pain (N.=33, 94.1%), which was successfully managed with acetaminophen and/or ketoprofen in 91.2%. In two cases, conservative management failed and a surgical approach was undertaken. Most women (N.=20, 90.9%) delivered at term, with a cesarean delivery and post-partum hemorrhage rate of 22.7%. All newborns had normal APGAR score, umbilical artery pH and birth weight. CONCLUSIONS: Pain is the most common complication of fibroids during pregnancy. Accurate differential diagnosis and adequate management are pivotal to ensure good perinatal outcomes.

Genomic Complexity and Complex Chromosomal Rearrangements in Genetic Diagnosis: Two Illustrative Cases on Chromosome 7.

Complex chromosomal rearrangements are rare events compatible with survival, consisting of an imbalance and/or position effect of one or more genes, that contribute to a range of clinical presentations. The investigation and diagnosis of these cases are often difficult. The interpretation of the pattern of pairing and segregation of these chromosomes during meiosis is important for the assessment of the risk and the type of imbalance in the offspring. Here, we investigated two unrelated pediatric carriers of complex rearrangements of chromosome 7. The first case was a 2-year-old girl with a severe phenotype. Conventional cytogenetics evidenced a duplication of part of the short arm of chromosome 7. By array-CGH analysis, we found a complex rearrangement with three discontinuous trisomy regions (7p22.1p21.3, 7p21.3, and 7p21.3p15.3). The second case was a newborn investigated for hypodevelopment and dimorphisms. The karyotype analysis promptly revealed a structurally altered chromosome 7. The array-CGH analysis identified an even more complex rearrangement consisting of a trisomic region at 7q11.23q22 and a tetrasomic region of 4.5 Mb spanning 7q21.3 to q22.1. The mother's karyotype examination revealed a complex rearrangement of chromosome 7: the 7q11.23q22 region was inserted in the short arm at 7p15.3. Finally, array-CGH analysis showed a trisomic region that corresponds to the tetrasomic region of the son. Our work proved that the integration of several technical solutions is often required to appropriately analyze complex chromosomal rearrangements in order to understand their implications and offer appropriate genetic counseling.

Cardiac and obstetric outcomes in pregnant women with heart disease: appraisal of the 2018 mWHO classification.

OBJECTIVE: To appraise the application of the 2018 European Society of Cardiology-adapted modified WHO (mWHO) classification to pregnant women with heart disease managed at our maternal-fetal medicine referral centre and to assess whether the lack of a multidisciplinary Pregnancy Heart team has influenced their outcomes. METHODS: A retrospective cohort study including all pregnancies with heart disease managed at our centre between June 2011 and December 2020. Cardiac conditions were categorised in five classes according to the mWHO classification. An additional class, named X, was created for conditions not included in this classification. Outcomes were compared among all classes and factors potentially associated to cardiac complications were assessed. RESULTS: We identified 162 women with 197 pregnancies, for a prevalence of 0.7%. Thirty-eight (19.3%) gestations were included in class X. Caesarean section was performed in 64.9% pregnancies in class X, a rate similar to that of class II, II-III, and III/IV, and mostly for obstetric indications; in turn, it was more commonly performed for cardiology reasons in class II-III and III/IV. Cardiac complications occurred in 10.7%, with class X and II pregnancies showing the highest number of events (n=30.8% and 34.6%, respectively). Multiple gestation and urgent caesarean section associated with a 5-fold and 6.5-fold increase in complication rates. CONCLUSIONS: Even in a maternal-fetal medicine referral centre, the lack of a multidisciplinary team approach to women with heart disease may negatively impact their outcomes.

A new case report of severe mucopolysaccharidosis type VII: diagnosis, treatment with haematopoietic cell transplantation and prenatal diagnosis in a second pregnancy.

A new patient with severe mucopolysaccharidosis (MPS) type VII is reported. Non-immune hydrops fetalis (NIHF) was diagnosed during pregnancy. At birth, he showed generalized hydrops and dysmorphic features typical of MPS. Many diagnoses were excluded before reaching the diagnosis of MPS VII at 8 months of life. During the first year of life he had frequent respiratory infections associated with restrictive and obstructive bronchopneumopathy and underwent three surgical interventions: decompression of the spinal cord at the craniocervical junction, bilateral inguinal hernia, and bilateral clubfoot. At 14 months of life he underwent successful haematopoietic cell transplantation (HCT). During the following 10 months, his bronchopneumopathy progressively worsened, needing chronic pharmacological treatment and O2 administration. The patient died of respiratory insufficiency during a respiratory syncytial virus infection at 25 months of age. Molecular analysis showed the homozygous variant c.1617C > T, leading to the synonymous mutation p.Ser539=. This caused aberrant splicing with partial skipping of exon 10 (r.1616_1653del38) and complete skipping of exon 9 (r.1392_1476del85; r.1616_1653del38). No transcript of normal size was evident. The parents were both confirmed to be carriers. In a subsequent pregnancy, a prenatal diagnosis showed an affected fetus. Ultrasound examination before abortion showed NIHF. The skin and placenta examination by electron microscopy showed foamy intracytoplasmic vacuoles with a weakly electron-dense substrate. MPS VII is a very rare disease but it is possible that some cases go undiagnosed for several reasons, including that MPS VII, and other lysosomal storage diseases, are not included in the work-up for NIHF in many institutions, and the presence of anasarca at birth may be confounding for the recognition of the typical facial characteristics of the disease. This is the eighth patient affected by MPS VII who has undergone HCT. It is not possible to draw conclusions about the efficacy of HCT in MPS VII. Treatment with enzyme replacement is now available and will probably be beneficial for the patients who have a milder form with no or little cognitive involvement. Increased awareness among clinicians is needed for prompt diagnosis and to offer the correct treatment as early as possible.

Large pericardial effusion in a family with recurrent pericarditis: A report of probable x-linked transmission.

Three cases of recurrent pleuropericarditis were observed within the same family - in two sisters and their niece, who were 18, 35 and 18 years of age, respectively. One patient was treated with pericardiectomy, and the other two were treated with colchicine. Mutations associated with autoinflammatory diseases (tumour necrosis factor receptor-associated periodic syndrome and familial Mediterranean fever) were absent; the condition was found to be sex linked.

Role of FISH on uncultured amniocytes for the diagnosis of aneuploidies in the presence of fetal anomalies.

OBJECTIVE: To assess the accuracy of fluorescent in situ hybridization (FISH) on amniocytes in fetuses affected by structural malformations suggestive of chromosomal anomalies. METHODS: FISH of uncultured amniotic fluid cells and conventional cytogenetic analysis were performed on 48 pregnancies with ultrasonographic (US) evidence of fetal anomalies. The AneuVysion assay (Vysis) with specific probes for chromosomes 13, 18, 21, X and Y, was used. Amniotic fluid samples were obtained between the 14th and 34th weeks of gestation. RESULTS: In cases with a single abnormal US finding (n = 15), 5 aneuploidies were detected (1 case of trisomy 13 and 4 of trisomy 21). In the group with two or more malformations (n = 33) there were 15 aneuploidies (9 cases of trisomy 18, 2 of trisomy 21, 2 monosomy X, 1 trisomy 13, and 1 triploidy). In this group, conventional cytogenetic analysis revealed two additional chromosomal anomalies not detectable by FISH (1 trisomy 16 mosaic, and a terminal deletion 4p). No sex aneuploidies were observed. CONCLUSIONS: The lack of false-positive diagnosis in the FISH analysis in our sample prompts us to consider interphase FISH as a useful tool in pregnancies at high risk for chromosomal aneuploidies. When FISH analysis is normal, the overall risk of chromosomal abnormalities is significantly reduced. However, the finding of two chromosomal anomalies undetectable by AneuVysion assay confirms the need for conventional chromosome analysis to complement FISH results. Moreover, the results collected here, in agreement with those already reported in the literature, indicate that FISH analysis on uncultured amniocytes can play an important role in counselling and decision-making, especially in cases at risk for aneuploidies, such as those with structural abnormalities at US.

A prospective study of the role of ultrasound in the management of adnexal masses in pregnancy.

OBJECTIVE: To assess the clinical relevance of adnexal masses in pregnancy and the usefulness of ultrasound in their management. DESIGN: A prospective study on pregnancy complicated by adnexal masses. SETTING: Department of Obstetrics and Gynaecology in Italy. POPULATION: 6636 women with pregnancy in utero followed in our clinic from January 1996 to December 1999. METHODS: From 1996 to 1999, all ovarian cysts with a diameter exceeding 3 cm were prospectively recorded and followed. The management was expectant except in case of symptoms or suspected malignant features. Cysts suggestive of borderline tumours were treated expectantly. MAIN OUTCOME MEASURES: Clinical relevance of adnexal masses in pregnancy, the outcome of these pregnancies and the usefulness of ultrasound examination in their management. RESULTS: We detected 82 cysts in 79 of 6636 women (1.2 in 100 term pregnancies). Sixty-eight women were asymptomatic at the time of diagnosis, whereas 11 (13.9%) were diagnosed because of pain. Diagnosis occurred in the first trimester for 57 cases and in the second or third trimester in 22 (27.8%). One-half of the cysts were simple and anechoic at ultrasound. Fifty-seven had a diameter not exceeding 5 cm. Forty-two cyst resolved in pregnancy without treatment. Three cysts required surgery within few days (torsion). One woman required laparotomy at the 37th week of gestation, due to torsion. When one case of termination was excluded, 78 women delivered at term (66 vaginally, 12 by caesarean section). Nineteen women underwent surgery after pregnancy. We recorded three Stage Ia borderline tumours, accounting for 3/82 cysts (3.6%) and 3/30 persisting masses (10%). CONCLUSION: Ultrasound allows definition of ovarian cysts in pregnancy and this positively impacts on management. The incidence of cancer among persistent masses is lower than previously reported. Acute complications in stable cysts are extremely uncommon after the first trimester. An expectant management is successful in the majority of cases and should be considered more often. Routine removal of persistent cysts is not justified.

La desaparición del luchecillo (egeria densa) del santuario del río Cruces (Valdivia, Chile): una hipótesis plausible / Decay of egeria densa (luchecillo) on the natur sanctuary of the Cruces river

El Santuario de la Naturaleza “Carlos Anwandter” (Valdivia, Chile) incluye el cauce del río Cruces, varios tributarios de él y zonas aledañas de inundación permanente (bañados). En dicho humedal existía una rica flora acuática y palustre, que albergaba una variada fauna, especialmente aves. En octubre de 2004 se denunció la muerte de algunos Cisnes de cuello negro y la migración de la mayoría de ellos, por escasez de alimento, constituido principalmente por el macrófito sumergido y arraigado al sustrato, Egeria densa, que había desaparecido de los bañados, pero se conservaba sumergido en los cauces. Los Cisnes de cuello negro sumergían cuerpo y cabeza tironeando las plantas, arrancándolas y ayudando así a su desaparición. La causa de la muerte en los bañados y profundización de Egeria densa en los cauces, es aún una incógnita, aunque se ha señalado como culpable a una industria de celulosa ubicada a orillas del río Cruces unos 30 km aguas arriba del humedal, que empezó sus actividades productivas en febrero de 2004. Se supone una contaminación con hierro, presente en los sedimentos y liberados por los riles de la industria. Las características de la posible contaminación del humedal no son típicas de una actividad industrial, que tampoco podría haberse presentado en tan corto plazo. La presencia de los mismos síndromes observados en el Santuario del río Cruces, en las lagunas (Grande y Chica) de San Pedro de la Paz en Concepción, 400 km más al Norte, indican una causa más generalizada. La sobrevivencia de plantas sumergidas, indican un factor atmosférico que se atenúa en profundidad. Ante estas y otras evidencias se hipotetiza que la causa de la muerte de Egeria densa sería la alta radiación UV-B en la región, aumentada por el paulatino adelgazamiento de la capa de ozono. Esta hipótesis deberá ser comprobada en la próxima primavera, época en que aumenta la radiación.