Mutation in MEOX1 gene causes a recessive Klippel-Feil syndrome subtype.

BACKGROUND: Klippel-Feil syndrome (KFS) is characterized by the developmental failure of the cervical spine and has two dominantly inherited subtypes. Affected individuals who are the children of a consanguineous marriage are extremely rare in the medical literature, but the gene responsible for this recessive trait subtype of KFS has recently been reported. RESULTS: We identified a family with the KFS phenotype in which their parents have a consanguineous marriage. Radiological examinations revealed that they carry fusion defects and numerical abnormalities in the cervical spine, scoliosis, malformations of the cranial base, and Sprengel's deformity. We applied whole genome linkage and whole-exome sequencing analysis to identify the chromosomal locus and gene mutated in this family. Whole genome linkage analysis revealed a significant linkage to chromosome 17q12-q33 with a LOD score of 4.2. Exome sequencing identified the G > A p.Q84X mutation in the MEOX1 gene, which is segregated based on pedigree status. Homozygous MEOX1 mutations have reportedly caused a similar phenotype in knockout mice. CONCLUSIONS: Here, we report a truncating mutation in the MEOX1 gene in a KFS family with an autosomal recessive trait. Together with another recently reported study and the knockout mouse model, our results suggest that mutations in MEOX1 cause a recessive KFS phenotype in humans.

A novel locus for restless legs syndrome on chromosome 13q.

BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor disorder in which affected individuals suffer from uncomfortable sensations and an urge to move their lower limbs; it occurs mainly in resting situations during the evening or at night. Multiple chromosomal loci have been mapped for RLS through family-based linkage analysis, and genome-wide association studies but causative mutations have not been identified yet. METHOD: We identified an RLS family from the eastern part of central Turkey which has 10 patients suffering from this syndrome. Whole genome linkage analysis was performed in family members who consented for study (9 affected and 2 unaffected). RESULTS: A theoretical maximum logarithm of the odds score of 3.29 was identified at chromosome 13q32.3-33.2. This result shows strong genetic linkage to this locus. CONCLUSIONS: We demonstrated a genetic linkage at chromosome 13 in a RLS family. Further investigation in this linkage area may reveal a causative gene leading to RLS phenotype and may illuminate the pathogenesis of this disease. This study supports the genetic heterogeneity in the pathogenesis of this syndrome.

Etanercept treatment enhances clinical and neuroelectrophysiological recovery in partial spinal cord injury.

PURPOSE: To investigate the effect of an anti-TNF-α agent (etanercept) on recovery processes in a partial spinal cord injury (SCI) model using clinical and electrophysiological tests. METHODS: Twenty-four New Zealand rabbits were divided into three groups: group 1 [SCI + 2 ml saline intramuscular (i.m.), n = 8], group 2 (SCI + 2.5 mg/kg etanercept, i.m., 2-4 h after SCI, n = 8) and group 3 (SCI + 2.5 mg/kg etanercept, i.m., 12-24 h after SCI, n = 8). Rabbits were evaluated before SCI, immediately after SCI, 1 week after, and 2 weeks after SCI, clinically by Tarlov scale and electrophysiologically by SEP. RESULTS: Tarlov scores of groups 2 and 3 were significantly better than group 1, 2 weeks after SCI. SEP recovery was significantly better in groups 2 and 3 than group 1, 2 weeks after SCI. CONCLUSIONS: These results show that blocking TNF-α mediated inflammation pathway by an anti-TNF-α agent enhances clinical and electrophysiological recovery processes in partial SCI model.

Intracranial arachnoid cyst family with autosomal recessive trait mapped to chromosome 6q22.31-23.2.

BACKGROUND: Arachnoid cysts are congenital fluid-filled compartments within the cerebrospinal fluid cisterns and cerebral fissures. They most commonly occur sporadically, and familial occurrence has rarely been reported. In this study, we showed the first genetic linkage in the literature in a pure intracranial arachnoid cyst family with autosomal recessive trait. METHODS: We identified an intracranial arachnoid cyst family in southern Turkey whose six of seven offspring had intracranial arachnoid cysts in different localizations, and collected venous blood from seven offspring of the family. Whole-genome linkage analysis was performed in all offspring. RESULTS: A theorical maximum logarithm of the odds score of 4.6 was identified at chromosome 6q22.31-23.2. This result shows strong genetic linkage to this locus. CONCLUSIONS: We present the first genetic linkage analysis result in a pure intracranial arachnoid cyst family in literature. Further investigation of this linkage area can reveal a causative gene causing the intracranial arachnoid cyst phenotype and can illuminate the pathogenesis of this disease.

Clipping of large and giant aneurysms of anterior circulation.

AIM: Surgical outcome for giant intracranial aneurysms (GIA) is suboptimal. Reasons for higher complication rates in large and GIA surgery are the occlusion of perforators or parent arteries during aneurysm clipping, or prolonged temporary occlusion of main arteries. In this article, results of clipping of large and GIAs of anterior circulation are presented. MATERIAL AND METHODS: Ten patients with large or GIAs in the anterior circulation were treated by clipping (10/19, 52%). The most common location was the middle cerebral artery (MCA, 5/10), followed by the anterior cerebral artery (ACA, 3/10), and internal carotid artery (ICA, 2/10). Five aneurysms were large (17-20 mm), five were giant (27-53 mm). RESULTS: Uneventful aneurysm clipping was performed in eight, and cure was obtained in nine patients. Mortality and morbidity figures were 10% (1/10), and 0% (0/10), respectively. Mean follow up time is 2.8 years (range 1-10 years). CONCLUSION: Clipping is still the most common surgical method of dealing with these lesions. Clipping of all large and giant aneurysms of anterior circulation was achieved in our patients with 10% mortality and 0% morbidity rates. These rates are similar to figures reported in previous series. Clipping of large and giant aneurysms is still the best definitive treatment, and is applicable in majority of the patients.

Myelopathy and Quadriparesis due to Spinal Cord Compression of C1 Laminar Osteochondroma.

The aim of this paper is to show that osteochondromas of the cervical vertebrae can cause myelopathy and neck pain.The reported etiology, diagnosis, treatment and differential diagnosis were reviewed. Osteochondromas may present as a solitary lesion with no genetic component or as multiple lesions as a part of a genetic disorder known as hereditary multiple exostosis. Osteochondromas of the spine are rarely encountered in clinical practice. These lesions are reported more commonly with neural compression in cases associated with hereditary multiple exostosis. The authors describe a unusual clinical manifestation of a solitary osteochondroma located in the right posterior arch of the atlas. Complete removal of the tumor was performed resulting in the relief of neck pain and spastic quadriparesis. Although unusual, osteochondromas of the cervical spine must be considered in patients with persistent neck pain and progressive symptoms of myelopathy. Computed tomography and magnetic resonance imaging in conjunction with plain radiograms is the neuroradiological modality of choice. The diagnosis and surgical excision of these tumors are important because they can cause spinal stenosis resulting in neural tissue compression and myelopathy.