Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Historical, physical, cognitive, and cytogenetic data were documented in 105 heterozygous fragile X [fra(X)] females and 90 controls in a prospective fashion. For comparisons, we divided heterozygotes and controls into those with cognitive impairment (IQ less than 85) and normal IQ (IQ greater than or equal to 85). The only finding that was significantly more frequent in impaired heterozygotes compared with impaired controls chi 2 analysis was shyness. Features that were more frequent in normal IQ heterozygotes compared with normal controls were voluntary thumb dislocation and hyperextensible metacarpal-phalangeal (MP) joints. Comparisons among heterozygotes demonstrated more math problems, hand biting, strabismus, high-arched palate, hyperextensible finger joints, and flat feet in impaired heterozygotes than in normal heterozygotes. Premature menopause was present in 8 of 61 normal heterozygotes and in none of the impaired heterozygotes. A multiple regression analysis demonstrated a significant inverse correlation between the percent fragility and IQ for the heterozygotes as a group. However, no correlation existed between IQ and fragility when the percent fragility was 2% or greater. However, a higher percentage of fragility was positively correlated with the total number of physical findings present.
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PMID:Heterozygous fragile X female: historical, physical, cognitive, and cytogenetic features. 201 71

Restless legs syndrome (RLS) exhibits sensorimotor symptoms. In familial cases, a gene at chromosomal location 9p-24-22 is linked to RLS and the expressed mutation is Dopamine Receptor Specific Individual Sensitivity (DRSIS). The symptoms are triggered during changes in alertness, generally at sleep hours, resulting from insufficient dopamine transmission. The conscious experience of sensory abnormalities are described as 'an urge to move the limbs with or without paresthesias' leading to motor signs such as periodic limb movements and motor restlessness which exhibit temporary loss of extensor motor system dominance over the flexor motor system of the upright posture. The relationship of the expressed mutation to EEG alpha activity makes RLS a sleep disorder as well as a cognitive dysfunction. The recurrent character of sensorimotor symptoms impede the patient's ability to sleep, wake and force to move leading to insomnia. In Uner Tan Syndrome, the nonsense mutation in the same gene leads to underdevelopment of the neural substrates of upright posture. The defects include dopamine receptor deficiency (DRD) leading to severe cognitive dysfunctions and motor disorders-complete loss of extensor motor system dominance over the flexor motor system-quadrupedality, primitive speech, cerebellar symptoms, and strabismus. Comparisons between the neural substrates of sensorimotor symptoms seen in RLS and MRI findings for cases of Uner Tan Syndrome show cortico-cerebellar hypoplasias in the neural networks involved in upright posture. Both RLS and Uner Tan Syndrome seem to be due to different mutations in the dopamine receptor gene at 9p-24 locus, affecting the diencephalon dopaminergic system and the neural networks involved in upright posture.
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PMID:In restless legs syndrome, the neural substrates of the sensorimotor symptoms are also normally involved in upright standing posture and biped walking. 1939 50

Thus far, the phenotype of tetrasomy 18p has been primarily delineated by published case series and reports. Findings reported in more than 25% of these cases include neonatal feeding problems, growth retardation, microcephaly, strabismus, muscle tone abnormalities, scoliosis/kyphosis, and variants on brain MRI. Developmental delays and cognitive impairment are universally present. The purpose of this study was to more fully describe tetrasomy 18p at both the genotypic and the phenotypic levels. Array CGH was performed on 43 samples from individuals with tetrasomy 18p diagnosed via routine karyotype. The medical records of 42 of these 43 individuals were reviewed. In order to gain additional phenotypic data, 31 individuals with tetrasomy 18p underwent a series of clinical evaluations at the Chromosome 18 Clinical Research Center. Results from the molecular analysis indicated that 42 of 43 samples analyzed had 4 copies of the entire p arm of chromosome 18; one individual was also trisomic for a section of proximal 18q. The results of the medical records review and clinical evaluations expand the phenotypic description of tetrasomy 18p to include neonatal jaundice and respiratory distress; recurrent otitis media; hearing loss; seizures; refractive errors; constipation and gastroesophageal reflux; cryptorchidism; heart defects; and foot anomalies. Additional findings identified in a small number of individuals include hernias, myelomeningocele, kidney defects, short stature, and failure to respond to growth hormone stimulation testing. Additionally, a profile of dysmorphic features is described. Lastly, a series of clinical evaluations to be considered for individuals with tetrasomy 18p is suggested.
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PMID:Tetrasomy 18p: report of the molecular and clinical findings of 43 individuals. 2080 40

The Zellweger spectrum disorders (ZSDs) are known to be severe disorders with onset in the newborn period or later in childhood, frequently resulting in death during childhood or adolescence. Here, we report a case of ZSD due to mutations in the PEX2 gene, with very mild phenotype. A 51-year-old Italian man was referred to us because of a clinical picture characterized by ataxia, areflexia, nystagmus, and strabismus, with childhood onset and slowly progressive course. The patient showed no cognitive impairment. Neurological examination revealed gait ataxia, dysarthria, dysmetria, areflexia, and bilateral pes cavus. Nerve conduction studies indicated a severe axonal sensorimotor polyneuropathy. Brain MRI showed marked cerebellar atrophy and absence of white matter involvement. MR spectroscopy uncovered a decreased N-acetyl aspartate peak. Biochemical analyses suggested a mild peroxisomal defect. Sequence analysis of the PEX2 gene identified two heterozygous mutations. The clinical phenotype of our patient differs from previously reported ZSD patients with PEX2 gene mutations and suggests that genetic screening of PEX2 is warranted in children and adults with otherwise unexplained autosomal recessive ataxia. MRI findings diverged from the "classic" spectrum observed in ZSDs. The moderate impairment in peroxisome biogenesis seems to affect predominantly neuronal cells in cerebellum, leading to cerebellar atrophy.
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PMID:Zellweger Spectrum Disorder with Mild Phenotype Caused by PEX2 Gene Mutations. 2343 Sep 38

CHL1 gene maps at 3p26.3 and encodes a cell adhesion molecule of the immunoglobulin superfamily highly expressed in the brain. CHL1 regulates neuronal migration and neurite overgrowth in the developing brain, while in mature neurons it accumulates in the axonal membrane and regulates synapse function via the clathrin-dependent pathways. To our knowledge, to date only three familial cases presenting heterozygous deletion of chromosome 3 at band p26.3, including only the CHL1 gene, have been reported. All the patients presented cognitive impairment characterized by learning and language difficulties. Here, we describe a six-year-old boy in which array-CGH analysis disclosed a terminal 3p26.3 deletion. The deletion was transmitted from his normal mother and included only the CHL1 gene. Our patient presented microcephaly, short stature, mild mental retardation, learning and language delay, and strabismus. In our study we compare the phenotypic and molecular cytogenetic features of CHL1 gene deletion cases. Verbal function developmental delay seems to be a common key finding. The concomitance of the genetic and phenotypic alterations could be a good evidence of a new emerging syndrome associated with the deletion of CHL1 gene alone, although the identification of new cases is required.
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PMID:Heterozygous deletion of CHL1 gene: detailed array-CGH and clinical characterization of a new case and review of the literature. 2545 13

ADAT3-related intellectual disability has been recently described in 24 individuals from eight Saudi families who had cognitive impairment and strabismus. Other common features included growth failure, microcephaly, tone abnormalities, epilepsy, and nonspecific brain abnormalities. A single homozygous founder mutation (c.382G>A:p.(V128M)) in the ADAT3 gene, which encodes a protein that functions in tRNA editing, was identified in all affected individuals. In this report, we present additional 15 individuals from 11 families (10 Saudis and 1 Emirati) who are homozygous for the same founder mutation. In addition to the universal findings of intellectual disability and strabismus, the majority exhibited microcephaly and growth failure. Additional features not reported in the original cohort include dysmorphic facial features (prominent forehead, up-slanted palpebral fissures, epicanthus, and depressed nasal bridge), behavioral problems (hyperactivity and aggressiveness), recurrent otitis media, and growth hormone deficiency. ADAT3-related intellectual disability is an important recognizable cause of intellectual disability in Arabia.
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PMID:ADAT3-related intellectual disability: Further delineation of the phenotype. 2684 63

Whipple's disease, a rare systemic infectious disorder, is complicated by the involvement of the central nervous system in about 5% of cases. Oscillations of the eyes and the jaw, called oculo-masticatory myorhythmia, are pathognomonic of the central nervous system involvement but are often absent. Typical manifestations of the central nervous system Whipple's disease are cognitive impairment, parkinsonism mimicking progressive supranuclear palsy with vertical saccade slowing, and up-gaze range limitation. We describe a unique patient with the central nervous system Whipple's disease who had typical features, including parkinsonism, cognitive impairment, and up-gaze limitation; but also had diplopia, esotropia with mild horizontal (abduction more than adduction) limitation, and vertigo. The patient also had gaze-evoked nystagmus and staircase horizontal saccades. Latter were thought to be due to mal-programmed small saccades followed by a series of corrective saccades. The saccades were disconjugate due to the concurrent strabismus. Also, we noted disconjugacy in the slow phase of gaze-evoked nystagmus. The disconjugacy of the slow phase of gaze-evoked nystagmus was larger during monocular viewing condition. We propose that interaction of the strabismic drifts of the covered eyes and the nystagmus drift, putatively at the final common pathway might lead to such disconjugacy.
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PMID:Novel Eye Movement Disorders in Whipple's Disease-Staircase Horizontal Saccades, Gaze-Evoked Nystagmus, and Esotropia. 2874 53

Allan-Herndon-Dudley syndrome is a rare X-linked neurologic condition caused by mutations in monocarboxylate transporter 8 ( MCT8), which leads to deficient thyroid hormone transport. Typical features include severe cognitive impairment, truncal hypotonia, spastic paraplegia, weakness, and speech difficulties. Minimal literature exists describing the ocular findings in patients with Allan-Herndon-Dudley syndrome. We describe 4 male siblings affected with Allan-Herndon-Dudley syndrome with a novel nonsense mutation (Q90X) in the MCT8 protein. All affected siblings presented with classic findings of Allan-Herndon-Dudley syndrome, and each of the siblings also developed intermittent esotropia. This group of affected siblings represents the first consistent documentation of strabismus in Allan-Herndon-Dudley syndrome, suggesting a possible association between this clinical finding and the neurologic syndrome.
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PMID:Intermittent Esotropia in 4 Patients With Allan-Herndon-Dudley Syndrome. 2971 7

Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare mitochondrial disorder characterized by MLASA. Variable features of this condition include failure to thrive, and developmental delay or intellectual disability. Additional symptoms consist of cognitive impairment, skeletal and dental abnormalities, delayed motor milestones, cardiomyopathy, dysphagia, and respiratory insufficiency. MLASA has previously been associated with mutations in pseudouridylate synthase 1 (PUS1) and YARS2. PUS1 encodes the nuclear PUS1 enzyme, which is located in both the nucleus and the mitochondria. PUS1 converts uridine into pseudouridine in several cytosolic and mitochondrial transfer RNA positions and increases the efficiency of protein synthesis in both compartments.In the present report, we report on 2 Turkish sisters 4 and 11 of years with an MLASA plus phenotype. Both patients have sideroblastic anemia, lactic acidosis, failure to thrive, developmental delay, and chronic diarrhea; in addition, the older sister has strabismus and skeletal anomalies. The sequencing of the PUS1 gene revealed a novel homozygous p.Glu311* mutation. The phenotype of the older sibling is also unique because of the strabismus and skeletal anomalies, when compared with her sister and other previously reported patients with MLASA. The structural differences in the nuclear versus mitochondrial isoforms of PUS1 and modifier genes may be implicated in the variability of the clinical presentations in MLASA. CONCLUSION:: This report adds to the growing number of mutations causing complex clinical manifestations of MLASA including lactic acidosis, sideroblastic anemia, chronic diarrhea, and myopathy.
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PMID:A Novel PUS1 Mutation in 2 Siblings with MLASA Syndrome: A Review of the Literature. 3228 5