Truncating CLCN1 mutations in myotonia congenita: variable patterns of inheritance.

INTRODUCTION: Myotonia congenita due to protein truncating CLCN1 mutations is associated with variable patterns of inheritance. METHODS: Three family kindreds are described, all of whom possess protein truncating mutations (Y33X, fs503X, R894X). One lineage also has coexistent R894X, A313T, and A320V mutations. RESULTS: The Y33X mutation kinship has autosomal recessive inheritance and a severe phenotype when homozygous. The fs503X family has autosomal dominant inheritance and a moderate-to-severe phenotype. The A313T mutation kindred also has autosomal dominant inheritance but expresses a mild phenotype, except for the more severely affected compound heterozygotes. CONCLUSIONS: Early truncating mutations precluding dimerization are expected to be autosomal recessive and express a severe phenotype, while later mutations may be variable. The pedigrees presented here demonstrate that intrafamilial phenotypic variability may result from a dosage effect of an additional mutation, not necessarily variable expressivity. Mutations that have unexpected patterns of inheritance may represent allelic variability.

Severe case and literature review of primary erythromelalgia: novel SCN9A gene mutation.

Erythromelalgia is a rare clinical syndrome characterized by intermittent heat, redness, swelling and pain more commonly affecting the lower extremities. Symptoms are mostly aggravated by warmth and are eased by a cold temperature. In some cases, symptoms can be very severe and disabling. Erythromelalgia can be classified as either familial or sporadic, with the familial form inherited in an autosomal dominant manner. Recently, there has been a lot of progress in studying Na(v)1.7 sodium channels (expressed mostly in the sympathetic and nociceptive small-diameter sensory neurons of the dorsal root ganglion) and different mutations affecting the encoding SCN9A gene that leads to channelopathies responsible for some disorders, including primary erythromelalgia. We present a severe case of progressive primary erythromelalgia caused by a new de novo heterozygous missense mutation (c.2623C>G) of the SCN9A gene which substitutes glutamine 875 by glutamic acid (p.Q875E). To our knowledge, this mutation has not been previously reported in the literature. We also provided a short literature review about erythromelalgia and Na(v) sodium channelopathies.

Unilateral myokymia of the tongue after radiation therapy for cervical nodal melanoma.

Hypoglossal neuropathy with associated myokymia as a delayed effect of radiation is a rare occurrence, presumably due to the relative resistance of cranial nerves to injury from irradiation. The authors describe the first case of myokymia of the unilateral tongue with myokymic discharges on needle electromyography after hypofractionated radiation therapy for an extracranial melanoma of the neck. The earlier onset of myokymia than previous cases may represent more direct radiation exposure due to radiation site or the higher radiation dosage administered for treatment of melanomas.

Comparison of accidental and nonaccidental traumatic head injury in children on noncontrast computed tomography.

OBJECTIVE: Mixed-density convexity subdural hematoma and interhemispheric subdural hematoma suggest nonaccidental head injury. The purpose of this retrospective observational study is to investigate subdural hematoma on noncontrast computed tomography in infants with nonaccidental head injury and to compare these findings in infants with accidental head trauma for whom the date of injury was known. PATIENTS AND METHODS: Two blinded, independent observers retrospectively reviewed computed tomography scans with subdural hematoma performed on the day of presentation on 9 infant victims of nonaccidental head injury (mean age: 6.8 months; range: 1-25 months) and on 38 infants (mean age: 4.8 months; range: newborn to 34 months) with accidental head trauma (birth-related: 19; short fall: 17; motor vehicle accident: 2). RESULTS: Homogeneous hyperdense subdural hematoma was significantly more common in children with accidental head trauma (28 of 38 [74%]; nonaccidental head trauma: 3 of 9 [33%]), whereas mixed-density subdural hematoma was significantly more common in cases of nonaccidental head injury (6 of 9 [67%]; accidental head trauma: 7 of 38 [18%]). Twenty-two (79%) subdural hematomas were homogeneously hyperdense on noncontrast computed tomography performed within two days of accidental head trauma, one (4%) was homogeneous and isodense compared to brain tissue, one (4%) was homogeneous and hypodense, and four (14%) were mixed-density. There was no statistically significant difference in the proportion of interhemispheric subdural hematoma, epidural hematoma, calvarial fracture, brain contusion, or subarachnoid hemorrhage. CONCLUSIONS: Homogeneous hyperdense subdural hematoma is more frequent in cases of accidental head trauma; mixed-density subdural hematoma is more frequent in cases of nonaccidental head injury but may be observed within 48 hours of accidental head trauma. Interhemispheric subdural hematoma is not specific for inflicted head injury.

Inhibitory network properties shaping the light evoked responses of cat alpha retinal ganglion cells.

Cat retinal ganglion cells of the Y (or alpha) type respond to luminance changes opposite those preferred by their receptive-field centers with a transient hyperpolarization. Here, we examine the spatial organization and synaptic basis of this light response by means of whole-cell current-clamp recordings made in vitro. The hyperpolarization was largest when stimulus spots approximated the size of the receptive-field center, and diminished substantially for larger spots. The hyperpolarization was largely abolished by bath application of strychnine, a blocker of glycinergic inhibition. Picrotoxin, an antagonist of ionotropic GABA receptors, greatly reduced the attenuation of the hyperpolarizing response for large spots. The data are consistent with a model in which (1) the hyperpolarization reflects inhibition by glycinergic amacrine cells of bipolar terminals presynaptic to the alpha cells, and perhaps direct inhibition of the alpha cell as well; and (2) the attenuation of the hyperpolarization by large spots reflects surround inhibition of the glycinergic amacrine by GABAergic amacrine cells. This circuitry may moderate nonlinearities in the alpha-cell light response and could account for some excitatory and inhibitory influences on alpha cells known to arise from outside the classical receptive field.