Susana Pereira

An explanation for another familial case of Rett syndrome: maternal germline mosaicism

Rett syndrome (RTT; OMIM#312750) is a severe neurodevelopmental disorder that affects mainly girls. It has an estimated incidence of 1:10 000–15 000 females. Mutations in the X-linked gene methyl CpG-binding protein 2 (MECP2) have been found in most patients. The most accepted explanation for the sex bias is that the Rett mutation in sporadic cases has its origin in the paternal germline X chromosome and can thus only be transmitted to females. The majority of cases are sporadic (99.5%) but some familial cases have been described. These cases can either be explained by germline mosaicism or by asymptomatic carrier mothers with skewing of X-inactivation towards the wild-type MECP2 allele. We describe one of the few familial cases of RTT in which a maternal germline mosaicism is the most likely explanation. The mutation p.Arg270fs (c.808delC) was identified in both a girl with classical RTT and her brother who had the severe neurological phenotype usually described in males. The mutation was absent in DNA extracted from blood of both parents. These type of events must be taken into consideration in the genetic counselling of families after the diagnosis of a first case of RTT in a female or a MECP2 mutation in a male.

Rett syndrome with and without detected MECP2 mutations: An attempt to redefine phenotypes

BACKGROUND The diagnosis of Rett syndrome (RTT) is based on a set of clinical criteria, irrespective of mutation status. The aims of this study were (1) to define the clinical differences existing between patients with Rett syndrome with (Group I) and without a MECP2 mutation (Group II), and (2) to characterize the phenotypes associated with the more common MECP2 mutations. PATIENTS AND METHODS We analyzed 87 patients fulfilling the clinical criteria for RTT. All were observed and videotaped by the same paediatric neurologist. Seven common mutations were considered separately, and associated clinical features analysed. RESULTS Comparing Group I and II, we found differences concerning psychomotor development prior to onset, acquisition of propositive manipulation and language, and evolving autistic traits. Based on age at observation, we found differences in eye pointing, microcephaly, growth, number of stereotypies, rigidity, ataxia and ataxic-rigid gait, and severity score. Patients with truncating differed from those with missense mutations regarding acquisition of propositive words and independent gait, before the beginning of the disease, and microcephaly, growth, foot length, dystonia, rigidity and severity score, at the time of observation. Patients with the R168X mutation had a more severe phenotype, whereas those with R133C showed a less severe one. Patients with R294X had a hyperactive behaviour, and those with T158M seemed to be particularly ataxic and rigid. CONCLUSION A clear regressive period (with loss of prehension and language, deceleration of growth) and the presence of more than three different stereotypies, rigidity and ataxic-rigid gait seemed to be very helpful in differentiating Group I from Group II.

Ipsilateral Basilic Vein Transposition in a Patient With a Pacemaker

Worldwide, the number of patients with end-stage renal disease (ESRD) who require hemodialysis treatment is growing. Patients aged greater than 65 years and with comorbidities are also increasing, especially those with diabetes and cardiovascular diseases. For these reasons, it is more common to see patients with cardiovascular implantable electronic devices (CIEDs) (1). In 2012, the CIEDs implantation rate prevalence in ESRD patients from the USA was 1.2% (2), especially pacemakers and implantable cardioverterdefibrillators. Pacemakers can cause central venous stenosis in up to 64% of patients (3). Generally, a pacemaker will preclude the use of the entire ipsilateral arm for vascular access (4), because of the higher risk of the patient developing symptoms of venous hypertension syndrome (swelling, edema and collateral circulation) (5). This situation can hamper the creation of an arteriovenous fistula (AVF), in patients without a vascular network in the contralateral arm or with previously unsuccessful arteriovenous access. However, many patients, at physical examination and ultrasound evaluation, have a vascular network (arterial and venous) compatible with creation of an AVF on the same side where the pacemaker is placed. This type of dilemma, to create or not to create an arteriovenous ipsilateral access in patients with a pacemaker, is frequent and the choice is difficult. In this report, we present a case of creating an AVF ipsilateral access in a patient with a pacemaker. The fistula created was a brachial-basilic, with basilic vein transposition in two stages.