Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype--phenotype correlation.
(17/222)
Mutations in FOXL2, a forkhead transcription factor gene, have recently been shown to cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II the eyelid defect occurs as an isolated entity. In this study, we describe the identification of novel mutations in the FOXL2 gene in BPES types I and II families, in sporadic BPES patients, and in BPES families where the type could not be established. In 67% of the patients studied, we identified a mutation in the FOXL2 gene. In total, 21 mutations (17 of which are novel) and one microdeletion were identified. Thirteen of these FOXL2 mutations are unique. In this study, we demonstrate that there is a genotype--phenotype correlation for either types of BPES by the finding that mutations predicted to result in a truncated protein either lacking or containing the forkhead domain lead to BPES type I. In contrast, duplications within or downstream of the forkhead domain, and a frameshift downstream of them, all predicted to result in an extended protein, cause BPES type II. In addition, in 30 unrelated patients with isolated POF no causal mutations were identified in FOXL2. Our study provides further evidence that FOXL2 haploinsufficiency may cause BPES types I and II by the effect of a null allele and a hypomorphic allele, respectively. Furthermore, we propose that in a fraction of the BPES patients the genetic defect does not reside within the coding region of the FOXL2 gene and may be caused by a position effect. (+info)
Adenosine A2A receptor antagonists are potential antidepressants: evidence based on pharmacology and A2A receptor knockout mice.
(18/222)
1. Adenosine, an ubiquitous neuromodulator, and its analogues have been shown to produce 'depressant' effects in animal models believed to be relevant to depressive disorders, while adenosine receptor antagonists have been found to reverse adenosine-mediated 'depressant' effect. 2. We have designed studies to assess whether adenosine A2A receptor antagonists, or genetic inactivation of the receptor would be effective in established screening procedures, such as tail suspension and forced swim tests, which are predictive of clinical antidepressant activity. 3. Adenosine A2A receptor knockout mice were found to be less sensitive to 'depressant' challenges than their wildtype littermates. Consistently, the adenosine A2A receptor blockers SCH 58261 (1 - 10 mg kg(-1), i.p.) and KW 6002 (0.1 - 10 mg kg(-1), p.o.) reduced the total immobility time in the tail suspension test. 4. The efficacy of adenosine A2A receptor antagonists in reducing immobility time in the tail suspension test was confirmed and extended in two groups of mice. Specifically, SCH 58261 (1 - 10 mg kg(-1)) and ZM 241385 (15 - 60 mg kg(-1)) were effective in mice previously screened for having high immobility time, while SCH 58261 at 10 mg kg(-1) reduced immobility of mice that were selectively bred for their spontaneous 'helplessness' in this assay. 5. Additional experiments were carried out using the forced swim test. SCH 58261 at 10 mg kg(-1) reduced the immobility time by 61%, while KW 6002 decreased the total immobility time at the doses of 1 and 10 mg kg(-1) by 75 and 79%, respectively. 6. Administration of the dopamine D2 receptor antagonist haloperidol (50 - 200 microg kg(-1) i.p.) prevented the antidepressant-like effects elicited by SCH 58261 (10 mg kg(-1) i.p.) in forced swim test whereas it left unaltered its stimulant motor effects. 7. In conclusion, these data support the hypothesis that A2A receptor antagonists prolong escape-directed behaviour in two screening tests for antidepressants. Altogether the results support the hypothesis that blockade of the adenosine A2A receptor might be an interesting target for the development of effective antidepressant agents. (+info)
Carotid cavernous fistula due to a ruptured intracavernous aneurysm of the internal carotid artery: treatment with selective endovascular occlusion of the aneurysm.
(19/222)
Intracavernous carotid artery aneurysms causing a carotid-cavernous fistula (CCF) are rare. These aneurysms usually cause neurological symptoms due to gradual expansion without rupture. If they do rupture they most often lead to a CCF instead of bleeding into the subarachnoid space. A patient is described with a ruptured intracavernous aneurysm causing a CCF resulting in acute onset of unilateral ophthalmoplegia. Selective coil embolisation of the aneurysm led to complete occlusion of the CCF with preservation of the internal carotid artery; symptoms resolved completely. (+info)
Basilar artery aneurysm with autonomic features: an interesting pathophysiological problem.
(20/222)
Unruptured cerebral aneurysms often present with neuro-ophthalmological symptoms but ocular autonomic involvement from an aneurysm of the posterior circulation has not previously been reported. A patient is described with a basilar artery aneurysm presenting with headache and unilateral autonomic symptoms. After angiographic coiling of the aneurysm there was a near complete resolution of these features. The relevant anatomy and proposed mechanism of autonomic involvement of what may be considered--from a pathophysiological perspective as a secondary trigeminal-autonomic cephalgia--is discussed (+info)
Bilateral linear scleroderma "en coup de sabre" associated with facial atrophy and neurological complications.
(21/222)
BACKGROUND: Linear scleroderma "en coup de sabre" (LSCS) usually affects one side of the face and head in the frontoparietal area with band-like indurated skin lesions. The disease may be associated with facial hemiatrophy. Various ophthalmological and neurological abnormalities have been observed in patients with LSCS. We describe an unusual case of LSC. CASE PRESENTATION: A 23 year old woman presented bilateral LSCS and facial atrophy. The patient had epileptic seizures as well as oculomotor and facial nerve palsy on the left side which also had pronounced skin involvement. Clinical features of different stages of the disease are presented. CONCLUSIONS: The findings of the presented patient with bilateral LSCS and facial atrophy provide further evidence for a neurological etiology of the disease and may also indicate that classic progressive facial hemiatrophy (Parry-Romberg syndrome) and LSCS actually represent different spectra of the same disease. (+info)
Psychosocial implications of blepharoptosis and dermatochalasis.
(22/222)
PURPOSE: To investigate, for the first time, the psychosocial implications of blepharoptosis and dermatochalasis. METHODS: Two hundred ten individuals rated whole-face photographs of a series of patients on the basis of 11 different personal characteristics: intelligence, throat, friendliness, health, trustworthiness, hard work, mental illness, financial success, attractiveness, alcoholism, and happiness. Preoperative and postoperative photographs of both male and female patients with bilateral blepharoptosis and/or dermatochalasis were used. The paired t test was used to compare preoperative and postoperative ratings on the 11 characteristics. RESULTS: The preoperative photographs were rated more negatively than the postoperative photographs (P < .01-P < .001) on all 11 characteristics for both male and female patients by the 210 study subjects. CONCLUSIONS: Members of society seem to view individuals with blepharoptosis and dermatochalasis negatively. These psychosocial attitudes may lead to unjust bias toward affected patients, and surgical correction likely provides benefits beyond improved visual function. (+info)
Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in vivo.
(23/222)
Fatty acid amides (FAAs) represent a class of neuromodulatory lipids that includes the endocannabinoid anandamide and the sleep-inducing substance oleamide. Both anandamide and oleamide produce behavioral effects indicative of cannabinoid activity, but only anandamide binds the cannabinoid (CB1) receptor in vitro. Accordingly, oleamide has been proposed to induce its behavioral effects by serving as a competitive substrate for the brain enzyme fatty acid amide hydrolase (FAAH) and inhibiting the degradation of endogenous anandamide. To test the role that FAAH plays as a mediator of oleamide activity in vivo, we have compared the behavioral effects of this FAA in FAAH(+/+) and (-/-) mice. In both genotypes, oleamide produced hypomotility, hypothermia, and ptosis, all of which were enhanced in FAAH(-/-) mice, were unaffected by the CB1 antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-di-chlorophenyl)-4-methyl-1H-pyrazol e-3-carboxamide hydrochloride (SR141716A) and occurred in CB1(-/-) mice. Additionally, oleamide displayed negligible binding to the CB1 receptor in brain extracts from either FAAH(+/+) or (-/-) mice. In contrast, anandamide exhibited a 15-fold increase in apparent affinity for the CB1 receptor in brains from FAAH(-/-) mice, consistent with its pronounced CB1-dependent behavioral effects in these animals. Contrary to both oleamide and anandamide, monoacylglycerol lipids exhibited equivalent hydrolytic stability and pharmacological activity in FAAH(+/+) and (-/-) mice. Collectively, these results indicate that FAAH is a key regulator, but not mediator of FAA activity in vivo. More generally, these findings suggest that FAAs represent a family of signaling lipids that, despite sharing similar chemical structures and a common pathway for catabolism, produce their behavioral effects through distinct receptor systems in vivo. (+info)
Ophthalmopathy in childhood Graves' disease.
(24/222)
AIMS: To study the ocular manifestations and their severity in children with Graves' disease. METHODS: All patients with Graves' disease having regular follow up in a paediatric endocrine clinic were recruited for the study. A comprehensive ophthalmic assessment including ocular motility, exophthalmometry, intraocular pressure (IOP), slit lamp, and fundus examinations was performed. RESULTS: 83 patients (72 female, 11 male) aged 16 years or below were examined. All are Chinese. Ocular symptoms occurred in 12 patients. Ocular signs of ophthalmopathy were documented in 52 patients (62.7%). Most of them presented with eyelid abnormalities such as lid oedema, lid lag, and lagophthalmos, whereas lower lid retraction was the commonest clinical sign noted (38.6%). Diffuse conjunctival injection was found in four patients (4.8%). 10 patients (12.0%) had mild proptosis of less than 3 mm. Only one patient (1.2%) had limited extraocular motility in extreme gaze. Punctate epithelial corneal erosions were reported in 11 patients (13.3%). CONCLUSIONS: This is the largest series on the ocular complications of childhood Graves' disease in the literature. Although 52 patients (62.7%) were identified with positive ocular changes, none of them had visual threatening complications or debilitating myopathy. (+info)