Biomedical subjects

Elias I Traboulsi

Publications and source records attributed to Elias I Traboulsi.

At least 19 recordsLinked to original sources

PubMed2026

Streamlining Diagnosis of Bardet-Biedl Syndrome: New Diagnostic Algorithm With Updated Criteria.

Considerable advances have been made in our understanding of Bardet-Biedl syndrome (BBS), particularly in its core clinical features and molecular genetics, warranting an update to the existing diagnostic criteria framework. Using a rigorous, evidence-based, and consensus-driven process, a multidisciplinary group of international experts and patient-led organizations developed an updated diagnostic algorithm. This algorithm provides practical, updated guidance for clinicians, including a pathway for accurately incorporating genetic findings into the diagnostic process. We recommend that a clinical diagnosis requires either 4 major criteria or 3 major and 2 minor criteria. Revised major criteria are retinal dystrophy, obesity (or overweight in individuals < 2 years old), congenital anomalies of the kidney and urinary tract or chronic kidney disease, hypogonadism/genital anomalies, neurodevelopmental/neurocognitive manifestations, and postaxial polydactyly. The diagnosis can also be established with a positive genetic testing result in patients exhibiting ≥ 1 major criterion, provided that genetic findings should be interpreted in the context of the patient's clinical presentation, age, family history, and overlap with related ciliopathies. These consensus criteria offer a simple algorithm incorporating updated definitions for major and minor criteria and genetic testing to support a timely and accurate diagnosis of patients with BBS, inform genetic counseling, and potentially facilitate earlier access to treatment. Trial Registration: CRIBBS Registry; ClinicalTrials.gov: NCT02329210.

Humans↗

PubMed2006

Introducing a new computer-based test for the clinical evaluation of color discrimination.

PURPOSE: To evaluate the Portal color sort test (PCST), a new computer-based test of color vision, by comparing it with a series of clinical tests of color vision in normal and color deficient subjects. DESIGN: Prospective clinical laboratory study. METHODS: Fifty-nine subjects with normal trichromatic vision or with congenital color vision defects underwent a series of color vision tests that included the 15-plate Ishihara test, the D-15 Farnsworth-Munsell test (D-15), the Farnsworth-Munsell 100-Hue test (FM 100-Hue), and the PCST under rigorous standardized conditions, as recommended by the respective manufacturers. The PCST generates a numerical discrimination score comparable to the FM 100-Hue. RESULTS: To test validity, discrimination scores generated by the PCST were compared with scores on the FM 100-Hue. The Spearman rank correlation between discrimination scores on the FM 100-Hue and the PCST was 0.8 (P < .001). Reliability was assessed by asking patients to retake the PCST at a later sitting. Patients retaking the PCST achieved similar scores on their second sitting as on the first. The correlation in the score between the two tests was 0.7 (95% confidence interval [CI]: 0.4-0.9, P < .001). Median (quartiles) time to complete the PCST was 3.1 minutes. This was faster than the FM 100-Hue time (P < .001), but slower than both the Ishihara and the D-15 (both P < .001). CONCLUSIONS: This study suggests that the PCST, a test of color vision deficiency, can be used effectively and reliably as a tool for screening (comparable to the Ishihara plates and the D-15) and grading (comparable to the FM 100-Hue) color discrimination ability.

Adolescent↗

PubMed2006

Bilateral macular lesions in a 10-year-old girl.

PURPOSE: To report a previously undescribed macular dystrophy. DESIGN: Single descriptive case report. METHODS: Presentation of clinical findings, including ophthalmoscopy, fluorescein angiography, full-field and multifocal electroretinography (ERG), optical coherence tomography (OCT), and visual fields. RESULTS: A 10 year-old Caucasian girl had peculiar reddish blotchy macular lesions bilaterally, associated with decreased visual acuity, and no family history of similar lesions. Fluorescein angiography was inconclusive and showed mottled hyperfluorescence in the macula. The full-field electroretinogram was normal, but multifocal ERG revealed diminished waveforms centrally. CONCLUSION: This is possibly a new macular dystrophy, the nature of which remains to be determined.

Child↗

PubMed2006

Mutation screen of the TUB gene in patients with retinitis pigmentosa and Leber congenital amaurosis.

TUB is the first identified member of the TULP family of four proteins with unknown function. A spontaneous mutation in murine tub causes retinal degeneration, obesity, and deafness. Mutations in another member of the TULP family, TULP1, are a cause of autosomal recessive retinitis pigmentosa (RP). These findings prompted us to investigate TUB as a candidate gene for RP and Leber congenital amaurosis (LCA). A mutation screen of the entire coding region of the TUB gene in 159 unrelated patients with autosomal recessive RP, 114 unrelated patients with simplex RP, and 21 unrelated patients with LCA uncovered 18 sequence variations. Of these, seven were missense mutations, six were isocoding changes, and five were intronic polymorphisms. All seven missense mutations were identified as heterozygous changes and no defect could be found in the other allele. None of the isocoding variants or intronic polymorphisms are predicted to create or destroy splice donor or acceptor sites based on splice-site prediction software. Although variant alleles of the TUB gene were found, none could be definitively associated with a specific retinal disease.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Intracranial vascular anomalies in patients with morning glory disk anomaly.

PURPOSE: An association between morning glory disk anomaly (MGDA) and intracranial vascular anomalies including Moyamoya disease has been recognized. We evaluated a series of patients with MGDA to ascertain the frequency of cerebrovascular anomalies. DESIGN: Retrospective observational case series. METHODS: We reviewed the neurologic histories and neuroimaging studies of twenty patients with MGDA at two institutions between 1982 and 2004. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain was performed on all patients who had not undergone neuroimaging. MRI/MRA studies done for 40 pediatric patients without MGDA were also evaluated for cerebrovascular anomalies. The prevalence of anomalies in the two groups was compared by Fisher exact test. RESULTS: Nine of 20 patients (45%) with MGDA had cerebrovascular anomalies. Anomalies ranged from agenesis of the A1 segment of the anterior cerebral artery to bilateral stenosis of the internal carotid arteries with moyamoya disease. Three patients underwent revascularization procedures. Ten of 40 patients (25%) in the control group had any intracranial vascular anomaly, whereas only two of 40 (5%) had an abnormality of the anterior circulation, the most common finding in the MGDA group. CONCLUSION: We recommend that all patients with MGDA undergo MRI/MRA or computerized tomographic angiography to detect vascular and structural brain anomalies. It may be unclear whether cerebrovascular anomalies represent isolated congenital anomalies or findings of progressive occlusive cerebrovascular disease. Follow-up imaging should be considered in patients with cerebrovascular anomalies and is clearly indicated if neurologic signs or symptoms are present.

Adolescent↗

PubMed2006

Intraoperative relaxed muscle positioning technique for strabismus repair in thyroid eye disease.

OBJECTIVE: To describe the outcomes of a relaxed muscle technique for treatment of dysthyroid strabismus. DESIGN: Retrospective consecutive case series. PARTICIPANTS: Twenty-four patients with thyroid-related orbitopathy (TRO) underwent strabismus surgery using a novel relaxed muscle technique. METHODS: Charts of all patients who underwent rectus muscle recession surgery using a relaxed muscle technique between 1997 and 2004 were reviewed. Twenty-four of 28 patients had more than 2 months of follow-up and were included. The extent of recession was determined by marking where the tendon naturally fell while the relaxed muscle rested freely on the globe with the eye in the primary position. The muscle was sutured to the globe at the mark. Linear regression was used to determine the correlation between the degree of strabismus and the amount of recession required to eliminate diplopia. MAIN OUTCOME MEASURES: Surgical outcomes were analyzed 2 months, 6 months, and 1 year after strabismus repair. Excellent success was defined as no diplopia in primary and reading gazes without prisms. Good outcome was defined as no diplopia in primary and reading positions with the use of <10 prism diopters. Poor outcome was defined as persistent diplopia in primary or reading positions despite prisms, or the inability of the patient to tolerate the necessary prisms. RESULTS: Twenty-four patients underwent 60 muscle recessions. Nine had diplopia without a history of orbital decompression, 8 had diplopia before decompression, and 7 developed diplopia only after orbital decompression. Twenty-one patients (87.5%) had an excellent final outcome. A clinically acceptable (excellent or good) final outcome was achieved in 24 of 24 patients (100%) after an average of 1.08 surgeries. All 7 patients who developed diplopia only after decompression had an excellent outcome. Linear regression did not show good correlation between the degree of strabismus and the amount of recession required to eliminate diplopia (maximum R2 = 0.7292). There were no complications. CONCLUSIONS: The relaxed muscle technique provides excellent ocular alignment and relief from diplopia in a majority of patients with TRO-associated strabismus. Patients who develop diplopia only after orbital decompression may have a higher success rate.

Adult↗

PubMed2006

Optic disc coloboma and localized chorioretinal defects in constitutional partial trisomy 8 mosaicism.

Constitutional partial trisomy 8 mosaicism is a rare chromosomal multisystem disorder with systemic and ophthalmologic manifestations. We report the case of a 15-year-old female mosaic for trisomy 8 who has unilateral colobomatous microphthalmia and multiple chorioretinal defects. These congenital anomalies have not been previously reported in association with constitutional partial trisomy 8 mosaicism.

Adolescent↗

PubMed2006

Etiology of vision loss in ganglioside GM3 synthase deficiency.

PURPOSE: To investigate the cause of vision loss in patients with ganglioside GM3 synthase deficiency, a newly described rare autosomal recessive infantile-onset symptomatic epilepsy syndrome associated with developmental stagnation and blindness. METHODS: We examined four children from two related Amish sibships. Molecular genetic analysis confirmed inheritance of the founder mutation. Electroretinography and fundus photography were obtained in two patients. RESULTS: Despite an initial suspicion of retinal degeneration, retinal function was found to be preserved in both patients and ERG amplitudes were within normal limits. Ophthalmoscopy showed bilateral optic atrophy in all patients. CONCLUSIONS: Vision loss in GM3 synthase deficiency results from central nervous system and optic nerve involvement. Retinal function appears to be otherwise normal into the teenage years.

Adolescent↗

PubMed2006

Ocular findings in Gillespie-like syndrome: association with a new PAX6 mutation.

BACKGROUND: Gillespie syndrome is a rare variant form of aniridia, characterized by mental retardation, nonprogressive cerebellar ataxia, and iris hypoplasia. Unlike the more common dominant and sporadic forms of aniridia, there have been no associated PAX6 mutations or Wilms' tumor reported in Gillespie syndrome patients. Ocular findings in 21 cases published since Gillespie's initial description in 1965 include iris and foveal hypoplasia, nystagmus, and small optic discs with pigmentary retinopathy. CASE REPORT: We herein report a case of atypical Gillespie syndrome associated with bilateral ptosis, exotropia, corectopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation. Neurologic evaluation revealed a mild hand tremor and learning disability, but no ataxia or cerebellar abnormalities on neuroimaging. Sequencing studies revealed a substitution in intron 2 of the PAX6 gene (IVS2 + 2T > A). To our knowledge, this is the first mutation of PAX6 gene reported in association with a Gillespie-like syndrome.

Abnormalities, Multiple↗

PubMed2006

Lumpers or splitters? The role of molecular diagnosis in Leber congenital amaurosis.

Clarification and classification of the congenital form of blindness known as Leber congenital amaurosis (LCA) continues to provide its challenges and dilemmas. Until recently, seven genes have been identified that cause LCA. Clarifying the relation between LCA and associated neurological abnormalities such as autism, seizures, and hypotony, and unraveling the relationship between the ocular LCA phenotype and that associated with distinct systemic entities such as Joubert syndrome, Senior-Loken syndrome and Saldino-Mainzer syndrome has taken on new importance with the discovery that a substantial proportion of patients with LCA have mutations in the CEP290 gene that causes Joubert syndrome. This commentary explores the implications of this recent discovery and revisits the classification of LCA.

Antigens, Neoplasm↗

PubMed2006

Heterozygous and homozygous mutations in PITX3 in a large Lebanese family with posterior polar cataracts and neurodevelopmental abnormalities.

PURPOSE: The PITX3 gene, which codes for a homeobox bicoidlike transcription factor is responsible for dominant cataract and anterior segment mesenchymal dysgenesis in humans. In the current study, a family with autosomal dominant posterior polar cataract (PPC) and a PITX3 mutation that cosegregates with the disease was examined. Also studied were two siblings who were homozygous for the PITX3 mutation who had microphthalmia and significant neurologic impairment. METHODS: A genome-wide screen, linkage analysis in the PITX3 chromosomal region 10q25, haplotype analysis, and sequencing of the PITX3 gene were performed on 28 affected and 14 unaffected member of a three-generation Lebanese family. RESULTS: Genome-wide linkage analysis showed a lod score of 3.56 at theta = 0.00 on chromosome 10 at area q25. Analysis of the haplotypes and phenotypes confined the disease locus to a region on 10q25 between the markers D10S1239 and D10S1268. A candidate gene, PITX3, maps to that region. Sequencing of the PITX3 gene revealed a heterozygous G deletion mutation in 25 of the 42 family members. In addition, two siblings from a consanguineous marriage were found to be homozygous for the deletion. CONCLUSIONS: This is the first report of homozygous PITX3 mutations in humans. The phenotype in these individuals highlights the role of PITX3 in ocular and central nervous system (CNS) development.

Cataract↗

PubMed2006

Ocular abnormalities in mice lacking the Ski proto-oncogene.

PURPOSE: Persistent hyperplastic primary vitreous (PHPV) is a developmental ocular malformation often associated with additional ocular abnormalities. This study involved a novel mouse model of PHPV, generated by a null mutation of the Ski proto-oncogene, that displays other anterior segment and retinal malformations often found in human cases of PHPV. METHODS: Morphologic and histologic analyses of Ski-/- mice were used to document ocular abnormalities in comparison to those of normal littermates. Immunohistochemical studies were used to examine the expression of relevant markers of ocular and vascular development including Pax6, beta-III tubulin, and Flk1. RESULTS: PHPV and microphthalmia were found in 100% of Ski-/- fetuses. Other abnormalities included anterior segment and lens dysgenesis, retinal folds, chorioretinal coloboma, and Peters anomaly. The severity was variable, even in a highly homogeneous genetic background. PHPV was characterized by the presence of retrolental fibrous and vascular tissue that did not express the neuronal marker beta-III tubulin, but was positive for Flk1 expression and contained no obviously pigmented cells. CONCLUSIONS: The results show that normal ocular development requires the function of the Ski proto-oncogene, and mice lacking Ski have many features associated with PHPV, and some similarities with Peters anomaly in humans. Defects in Ski-/- mice closely resemble those described in animals lacking several of the retinoic acid receptor genes, or in animals exposed to excess retinoic acid during gestation. Ski has been shown to repress transcription induced by retinoic acid signaling, and may thus affect ocular development by regulating RA signaling.

Abnormalities, Multiple↗

PubMed2006

Association of optic nerve hypoplasia with mitochondrial cytopathies.

Ocular complications are common in the mitochondrial cytopathies and include optic atrophy and retinal degeneration. We retrospectively reviewed 80 patients with nonsyndromic mitochondrial cytopathies (ie, not Kearns-Sayre syndrome, myoclonus epilepsy associated with ragged red fibers [MERRF], mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes [MELAS], neuropathy ataxia and retinitis pigmentosa, Leigh disease, maternally inherited diabetes and deafness, and myoneurogastrointestinal disorder and encephalopathy) and found 10 cases of optic nerve hypoplasia. Optic nerve hypoplasia occurs in at least 12% of patients with nonsyndromic mitochondrial cytopathies. Although the exact pathogenesis of optic nerve hypoplasia in the context of mitochondrial cytopathy is unknown, we postulate that it is the result of excessive apoptosis during embryonic ganglion cell and/or axonal development from abnormal mitochondrial function and cellular energy metabolism.

Adolescent↗

PubMed2006

Systemic and ocular findings in 100 patients with optic nerve hypoplasia.

To describe associated ocular, neurologic, and systemic findings in a population of children with optic nerve hypoplasia, a retrospective chart review of 100 patients with optic nerve hypoplasia for the presence of neurologic, radiologic, and endocrine abnormalities was performed. Neuroimaging and endocrine studies were obtained in 65 cases. Visual acuity and associated ocular, neurologic, endocrine, systemic, and structural brain abnormalities were recorded. Seventy-five percent had bilateral optic nerve hypoplasia. Conditions previously associated with optic nerve hypoplasia and present in our patients include premature birth in 21%, fetal alcohol syndrome in 9%, maternal diabetes in 6%, and endocrine abnormalities in 6%. Developmental delay was present in 32%, cerebral palsy in 13%, and seizures in 12%. Of those imaged, 60% had an abnormal study. Neuroimaging showed abnormalities in ventricles or white- or gray-matter development in 29 patients, septo-optic dysplasia in 10, hydrocephalus in 10, and corpus callosum abnormalities in 8. There was an associated clinical neurologic abnormality in 57% of patients with bilateral optic nerve hypoplasia and in 32% of patients with unilateral optic nerve hypoplasia. Patients with unilateral and bilateral optic nerve hypoplasia frequently have a wide range and common occurrence of concomitant neurologic, endocrine, and systemic abnormalities.

Abnormalities, Multiple↗

PubMed2005

Optic atrophy and sensorineural hearing loss in a family caused by an R445H OPA1 mutation.

Autosomal dominant optic atrophy (ADOA) is the most common form of inherited optic atrophy. Four genetic loci have been associated with ADOA: OPA1, OPA2, OPA3, and OPA4. Out of these four loci, only one gene has been identified, OPA1. We previously described a unique syndrome of optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia in two unrelated families associated with an R445H mutation in OPA1. The R445H mutation is the only OPA1 mutation that has been associated with this syndrome. In this manuscript, we clinically characterize an unrelated family with four members affected by optic atrophy and hearing loss without extraocular motility abnormalities or ptosis. This family also harbors the R445H mutation. These cases help illustrate the intra- and inter-family variability in phenotype associated with this mutation. As we continue to learn more about OPA1 and the function of its protein product, we will begin to understand the pathophysiology of optic atrophy. This understanding will ultimately lead to novel treatments directed toward preventing the visual loss and disability associated with this inherited disease.

Adult↗

PubMed2005

SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies.

The SOX2 transcription factor is expressed early in the embryonic stem cells of the blastocyst and later in the neural stem cells. It is a member of the SOX family of proteins that carry a DNA-binding high-mobility group domain and additional domains that regulate embryonic development and cell fate determinations. We surveyed 93 patients with severe eye malformations for mutations in SOX2. Here, we report a novel nonsense mutation in one female patient with bilateral clinical anophthalmia, absence of all optic pathways, and other neurological abnormalities. The mutation, Q155X, creates a premature termination codon early in the transcriptional activation domain and is likely to be a null allele. Our data show that mutations in SOX2 can cause not only anophthalmia, but also aplasia of the optic nerve, chiasm and optic tract, as well as modest bilateral sensorineural hearing loss, and global developmental delay, underscoring the importance of SOX2 in early human eye and brain development.

Abnormalities, Multiple↗

PubMed2005

PHACE syndrome: report of a case with a glioma of the anterior skull base and ocular malformations.

PHACE syndrome consists of the constellation of manifestations including Posterior fossa anomalies of the brain (most commonly Dandy-Walker malformations), Hemangiomas of the face and scalp, Arterial abnormalities, Cardiac defects, and Eye anomalies. We present the case of a patient who presented with respiratory distress at birth secondary to a large nasal glioma. She was subsequently found to have a ventricular septal defect (VSD), a facial hemangioma, and a malformation of the eye and optic nerve head. The nasal glioma, which extended to the cribriform plate, has not been described in this syndrome. The tumor was resected through a coronal incision, midline nasal bone osteotomy, and a retrograde dissection from the nasal bones to the anterior skull base. Glioma of the skull base is a novel and serious manifestation of this uncommon condition.

Anti-Inflammatory Agents↗

PubMed2005

Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein.

Nanophthalmos is a rare disorder of eye development characterized by extreme hyperopia (farsightedness), with refractive error in the range of +8.00 to +25.00 diopters. Because the cornea and lens are normal in size and shape, hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina. Thickening of these tissues is a general feature of axial hyperopia, whereas the opposite occurs in myopia. We have mapped recessive nanophthalmos to a unique locus at 11q23.3 and identified four independent mutations in MFRP, a gene that is selectively expressed in the eye and encodes a protein with homology to Tolloid proteases and the Wnt-binding domain of the Frizzled transmembrane receptors. This gene is not critical for retinal function, as patients entirely lacking MFRP can still have good refraction-corrected vision, produce clinically normal electro-retinograms, and show only modest anomalies in the dark adaptation of photoreceptors. MFRP appears primarily devoted to regulating axial length of the eye. It remains to be determined whether natural variation in its activity plays a role in common refractive errors.

Animals↗