The m.8344A>G mutation in the MTTK gene, which encodes the mitochondrial transfer RNA for lysine, is traditionally associated with myoclonic epilepsy and ragged-red fibres (MERRF), a multisystemic mitochondrial disease that is characterised by myoclonus, seizures, cerebellar ataxia, and mitochondrial myopathy with ragged-red fibres. We studied the clinical and paraclinical phenotype of 34 patients with the m.8344A>G mutation, mainly derived from the nationwide mitoREGISTER, the multicentric registry of the German network for mitochondrial disorders (mitoNET). Mean age at symptom onset was 24.5 years ±10.9 (6-48 years) with adult onset in 75 % of the patients. In our cohort, the canonical features seizures, myoclonus, cerebellar ataxia and ragged-red fibres that are traditionally associated with MERRF, occurred in only 61, 59, 70, and 63 % of the patients, respectively. In contrast, other features such as hearing impairment were even more frequently present (72 %). Other common features in our cohort were migraine (52 %), psychiatric disorders (54 %), respiratory dysfunction (45 %), gastrointestinal symptoms (38 %), dysarthria (36 %), and dysphagia (35 %). Brain MRI revealed cerebral and/or cerebellar atrophy in 43 % of our patients. There was no correlation between the heteroplasmy level in blood and age at onset or clinical phenotype. Our findings further broaden the clinical spectrum of the m.8344A>G mutation, document the large clinical variability between carriers of the same mutation, even within families and indicate an overlap of the phenotype with other mitochondrial DNA-associated syndromes.

AbstractBackgroundThe main objective of this retrospective analysis in a large tertiary center was the clinical outcome of prenatally diagnosed cardiac rhabdomyomas as well as the identification of factors influencing fetal prognosis.MethodsA total of 45 cases of fetuses with prenatally suspected rhabdomyoma and their clinical outcome were analyzed retrospectively. A review of the literature was also performed.ResultsIn five cases, after a tuberous sclerosis complex (TSC) mutation had been confirmed, termination of pregnancy was chosen. In 30 cases postnatal data were available. In 93% TSC was confirmed clinically or by mutational analysis. Two thirds of fetuses presented with multiple tumor while one third presented with a solitary tumor. In two fetuses mild pericardial effusions were observed. Another three fetuses presented with extrasystoles prenatally. No hydrops fetalis or fetal perinatal demise were observed. After birth 41% of the children suffered from arrhythmia including supra- and ventricular tachycardia, Wolff-Parkinson-White syndrome and atrioventricular block. One child received a Fontan procedure with Glenn anastomosis. Another child with a dilatative cardiomyopathy and a left ventricular ejection fraction of 15% died. Fifty-two percent of the children with TSC suffered from epilepsy ranging from absence epilepsy and West syndrome to generalized seizures with a frequency of up to 40 per day. Two children underwent neurosurgery to remove the epileptogenic focus. One child suffered from TSC and Lesch-Nyhan disease. In another case Beckwith-Wiedemann syndrome was identified as the causative disorder.ConclusionRhabdomyoma are rare, benign tumors. There is an association with TSC. In the majority of cases rhabdomyoma are not hemodynamically relevant and do not increase in size. The quality of life of affected patients is impaired particularly due to epilepsy and psychomotor retardation.

We report the case of a fetus with sonographic characteristics of Beckwith‐Wiedemann syndrome (BWS). A 30‐year‐old gravida 2 para 1 was referred to our fetal medicine unit with an omphalocele. Fetal macrosomia, organomegaly, and polyhydramnios but no macroglossia were detected and BWS was suspected. Genetic testing for BWS did not confirm the suspected diagnosis as the karyotype was normal. Symptomatic polyhydramnios led to repeated amnioreductions. At 35 + 5 weeks of gestation, a female neonate of 3660 g was delivered with APGAR scores of 6/7/8, after 1/5/10 min, respectively. The abnormal shape of the thorax, facial dysmorphism, need for ventilation, and generalized muscular hypotonia led to the suspicion of Kagami‐Ogata syndrome (KOS), which was confirmed by genetic testing. KOS in our patient was caused by a large deletion in the MEG3‐region on chromosome 14q32 affecting the maternal allele. In this report, we highlight the notion that when sonographic signs suggestive of BWS such as macrosomia, polyhydramnios, and omphalocele are present and genetic testing does not confirm the suspected diagnosis, KOS should be tested for.

Background When discussing termination of pregnancy (TOP) after the first trimester, the main foci are the ethics and psychological reasoning/consequences. In daily clinical practice, physicians are often faced with affected women querying the frequency of their condition(s) and decisions made by women in similar situations. The present study aimed to provide an overview of a representable number of such cases. Methods Cases of TOP beyond 14 + 0 weeks of gestation were collected between January 2000 and December 2017 in the Department of Obstetrics. Fetal and/or maternal medical causes leading to TOP were extracted and presented. Results A total of 1746 TOPs ≥14 + 0 weeks were performed. Reasons leading to TOP were subcategorized into 23 groups. The main medical diagnoses were trisomy 21 (15.5%), neurological malformations (11.0%), and cardiac and major vessel malformations (7.9%). There was no statistical difference concerning maternal age or gravida/para between the groups. The average gestational age (GA) was 21.0 weeks, varying between 16.2 and 24.2 weeks in the 23 subgroups, with an average of 23.6% per year of TOPs after viability. Conclusion An overview of the various causes of TOP and their frequency within a large dataset are shown here. According to data provided by the German Federal Statistical Office, the overall number of TOPs has declined over the past two decades; however, the number and percentage of TOPs beyond viability have increased continuously in Germany. Only early detection of maternal and fetal constitution can prevent a portion of TOP after viability.

ObjectiveThe international Charité-MAYO Conference aims to promote international dialog on diagnostics, management, scientific breakthroughs, and state-of-the-art surgical procedures in gynecology and gynecologic oncology and senology. Live surgeries are a fundamental tool of interdisciplinary and international exchange of experts in their respective fields. Currently, there is a controversial and emotional debate about the true value, risks, and safety of live surgical broadcasts. The aim of the current study is to analyze peri-operative risks in patients who were operated live during the Charité-MAYO Conferences.MethodsLive surgeries were performed by the core Charité team consisting of gynecologic oncologic surgeons, breast and plastic surgeons, partly in collaboration with visiting gynecologic oncologic surgeons. We performed a retrospective analysis of live surgeries performed during seven Charité-MAYO Conferences from 2010 to 2019 held in Berlin, Germany. Patients’ files and tumor databases were analyzed as required and patients were contacted to update their long-term follow-up.ResultsSixty-nine patients who were operated live were included. The types of surgery were as follows: urogynecologic procedures (n=13), breast surgery (n=21), and gynecologic oncology surgery for ovarian, uterine, vulvar or cervical cancer (n=35). Peri-operative complications were assessed according to the Clavien–Dindo classification. Despite a high rate of complete resection and the high frequency of multivisceral procedures, the rate of peri-operative complications was within the range published in the literature. Time of surgery and length of intensive unit care and hospital stay did not differ from data acquired at the home institution.ConclusionsBased on our analysis, live surgeries appear to be safe when performed within a multidisciplinary setting without an increase in surgical morbidity and mortality compared with historical controls and without compromise of patients’ outcome. This is the first analysis of its kind to set the basis for patient information and consent for this type of surgeries.