Clinical and radiological characterization of novel FIG4-related combined system disease with neuropathy.

Variants in the FIG4 gene, which encodes a phosphatidylinositol-3,5-bisphosphatase lead to obstruction of endocytic trafficking, causing accumulation of enlarged vesicles in murine peripheral neurons and fibroblasts. Bi-allelic pathogenic variants in FIG4 are associated with neurological disorders including Charcot-Marie-Tooth disease type-4J (CMT4J) and Yunis-Varón syndrome (YVS). We present four probands from three unrelated families, all homozygous for a recurrent FIG4 missense variant c.506A>C p.(Tyr169Ser), with a novel phenotype involving features of both CMT4J and YVS. Three presented with infant-onset dystonia and one with hypotonia. All have depressed lower limb reflexes and distal muscle weakness, two have nerve conduction studies (NCS) consistent with severe sensorimotor demyelinating peripheral neuropathy and one had NCS showing patchy intermediate/mildly reduced motor conduction velocities. All have cognitive impairment and three have swallowing difficulties. MRI showed cerebellar atrophy and bilateral T2 hyperintense medullary swellings in all patients. These children represent a novel clinicoradiological phenotype and suggest that phenotypes associated with FIG4 missense variants do not neatly fall into previously described diagnoses but can present with variable features. Analysis of this gene should be considered in patients with central and peripheral neurological signs and medullary radiological changes, providing earlier diagnosis and informing reproductive choices.

The effect of different low-frequency filters on concentric needle jitter in stimulated orbicularis oculi.

INTRODUCTION: Our objective was to compare the effect of different low-frequency filters on jitter parameters when stimulating the orbicularis oculi. METHODS: Ten healthy volunteers were studied. Jitter was expressed as the mean consecutive difference (MCD). The low filter settings compared were 1, 2, and 3 kHz. RESULTS: No significant difference in mean MCD or outliers was found with the different filter settings. No significant difference in mean MCD was seen when the number of potentials analyzed was reduced. CONCLUSION: Different low-frequency settings do not influence the mean MCD when using a peak detection system. Muscle Nerve 54: 317-319, 2016.

Mice lacking the giant protocadherin mFAT1 exhibit renal slit junction abnormalities and a partially penetrant cyclopia and anophthalmia phenotype.

While roles in adhesion and morphogenesis have been documented for classical cadherins, the nonclassical cadherins are much less well understood. Here we have examined the functions of the giant protocadherin FAT by generating a transgenic mouse lacking mFAT1. These mice exhibit perinatal lethality, most probably caused by loss of the renal glomerular slit junctions and fusion of glomerular epithelial cell processes (podocytes). In addition, some mFAT1(-/-) mice show defects in forebrain development (holoprosencephaly) and failure of eye development (anophthalmia). In contrast to Drosophila, where FAT acts as a tumor suppressor gene, we found no evidence for abnormalities of proliferation in two tissues (skin and central nervous system [CNS]) containing stem and precursor cell populations and in which FAT is expressed strongly. Our results confirm a necessary role for FAT1 in the modified adhesion junctions of the renal glomerular epithelial cell and reveal hitherto unsuspected roles for FAT1 in CNS development.

Advances in EEG: home video telemetry, high frequency oscillations and electrical source imaging.

Over the last two decades, technological advances in electroencephalography (EEG) have allowed us to extend its clinical utility for the evaluation of patients with epilepsy. This article reviews three main areas in which substantial advances have been made in the diagnosis and pre-surgical planning of patients with epilepsy. Firstly, the development of small portable video-EEG systems have allowed some patients to record their attacks at home, thereby improving diagnosis, with consequent substantial healthcare and economic implications. Secondly, in specialist centres carrying out epilepsy surgery, there has been considerable interest in whether bursts of very high frequency EEG activity can help to determine the regions of the brain likely to be generating the seizures. Identification of these discharges, initially only recorded from intracranial electrodes, may thus allow better surgical planning and improve surgical outcomes. Finally we discuss the contribution of electrical source imaging in the pre-surgical evaluation of patients with focal epilepsy, and its prospects for the future.