Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children with genetic syndromes frequently have feeding problems and swallowing dysfunction as a result of the complex interactions between anatomical, medical, physiological, and behavioral factors. Feeding problems associated with genetic disorders may also cause feeding to be unpleasant, negative, or even painful because of choking, coughing, gagging, fatigue, or emesis, resulting in the child to stop eating and to develop behaviors that make it difficult, if not impossible, for a parent to feed their child. In addition, limited experiences with oral intake related to the medical or physical conditions, or other variables such as prematurity, often result in a failure of the child's oral motor skills to develop normally. For example, a child with Pierre Robin sequence may be unable to successfully feed orally, initially, due to micrognathia and glossoptosis. Oral-motor dysfunction may develop as a result of both anatomical problems, (e.g., cleft lip/palate), lack of experience (e.g., s/p. surgery), or oral motor abnormalities (e.g., brain malformation). Neuromotor coordination impairments such as those associated with Down syndrome (e.g., hypotonia, poor tongue control, and open mouth posture) frequently interfere with the acquisition of effective oral-motor skills and lead to feeding difficulties. Management of these phenomena is frequently possible, if an appropriate feeding plan exist that allows for three primary factors: (1) feeding program must be safe, (2) feeding program must support optimal growth, and (3) feeding program must be realistic. Researchers have demonstrated the utility of behavioral approaches in the treatment of feeding disorders, such as manipulations in the presentation of foods and drink and consequences for food refusal and acceptance (e.g., praise, extinction, contingent access to preferred foods). However, because a child's failure to eat is not frequently the result of a single cause, evaluation and treatment are typically conducted by an interdisciplinary team usually consisting of a behavioral psychologist, pediatric gastroenterologist, speech pathologist, nutrition, and sometimes other disciplines. This chapter provides an overview of some of the feeding difficulties experience by some of the more common genetic disorders including identification, interventions, and management.
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PMID:Feeding and swallowing dysfunction in genetic syndromes. 1864 13

During gait acquisition, children learn to use their changing resources to meet the requirements of the task. Compared to typically developing toddlers (TD), toddlers with Down syndrome (DS) have functionally different musculoskeletal characteristics, such as hypotonia, and joint and ligament laxity, that could produce a reduced passive stiffness. The interplay between this inherently lower passive stiffness and the demands of walking may result in different strategies during gait acquisition. This study compared normalized global stiffness and lower limb's co-contraction indices (CCI) used by toddlers with TD (n=12) and with DS (n=12), during the early stages of gait acquisition. Stiffness and CCI were normalized by gravitational torque (mLg) in both phases of gait (stance, swing). Five longitudinal evaluations were conducted from the onset of locomotion until three months post-acquisition. All children were video taped and had electromyographic (EMG) recordings from muscle pairs of one leg, which were used to calculate CCI of hip, knee, ankle, and total leg CCI. Body and lower limb stiffness were calculated according to a hybrid pendulum resonance equation. Results from ANOVAs revealed no group differences on stiffness or on CCI's during stance but children with DS showed greater CCI during swing. Despite the structural musculoskeletal differences between toddlers with TD and with DS, the similarities observed in their processes of gait development suggest functional equivalences.
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PMID:Changes in lower limb co-contraction and stiffness by toddlers with Down syndrome and toddlers with typical development during the acquisition of independent gait. 1864 65

Mutations in several steps of de novo purine synthesis lead to human inborn errors of metabolism often characterized by mental retardation, hypotonia, sensorineural hearing loss, optic atrophy, and other features. In animals, the phosphoribosylglycinamide transformylase (GART) gene encodes a trifunctional protein carrying out 3 steps of de novo purine synthesis, phosphoribosylglycinamide synthase (GARS), phosphoribosylglycinamide transformylase (also abbreviated as GART), and phosphoribosylaminoimidazole synthetase (AIRS) and a smaller protein that contains only the GARS domain of GART as a functional protein. The GART gene is located on human chromosome 21 and is aberrantly regulated and overexpressed in individuals with Down syndrome (DS), and may be involved in the phenotype of DS. The GART activity of GART requires 10-formyltetrahydrofolate and has been a target for anti-cancer drugs. Thus, a considerable amount of information is available about GART, while less is known about the GARS and AIRS domains. Here we demonstrate that the amino acid residue glu75 is essential for the activity of the GARS enzyme and that the gly684 residue is essential for the activity of the AIRS enzyme by analysis of mutations in the Chinese hamster ovary (CHO-K1) cell that require purines for growth. We report the effects of these mutations on mRNA and protein content for GART and GARS. Further, we discuss the likely mechanisms by which mutations inactivating the GART protein might arise in CHO-K1 cells.
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PMID:Mutations in the Chinese hamster ovary cell GART gene of de novo purine synthesis. 1900 68

During the development of walking, toddlers with Down syndrome (DS) and typical development (TD) face challenges controlling muscles, joints, and body segments. Toddlers with DS have additional challenges including increased joint laxity and decreased muscle tone and show delayed walking onset; the underlying activity of the neuromotor system remains unclear. Here we investigated the emergence of muscle activity from walking onset through 6 months of practice in eight toddlers with DS and eight with TD. We monitored the activity of core gait muscles and motion of leg segments as toddlers walked at their self-selected speeds. At walking onset muscle bursts were frequent with inconsistent burst durations. Over time, both groups of toddlers began to activate their leg muscles by using energy-efficient strategies: decreased muscle burst frequency (Wilks' Lambda=0.364, F(12, 103.476)=4.009, p< .001) and increased muscle burst duration (Wilks' Lambda=0.346, F(12, 71.727)=2.946, p= .002). Toddlers with TD increased normalized inter-burst intervals over time but toddlers with DS decreased these interval durations. By 6 months of experience toddlers with TD showed an efficient synergy among muscles, allowing increased relaxation time between bursts. Toddlers with DS improved the rhythmicity of their muscle burst, sustaining longer bursts but timing remained inconsistent. We propose increased muscle burst duration in toddlers with DS may add control by stabilizing their lax joints. Thus, their similar yet different emergent strategy may reflect their unique biomechanical and neurophysiological constraints and represent an efficient control strategy.
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PMID:Emergence of neuromuscular patterns during walking in toddlers with typical development and with Down syndrome. 1927 65

Down syndrome has a prevalence of one in 500 to one in 1,000 live births and is the most common cause of mental retardation. Most patients are treated in childhood and adolescence for mental or growth retardation. Studies that evaluate bone mass in Down syndrome are limited, and many are small case series in pediatric and adult populations who live either in the community or in residential institutions. Several environmental and hormonal factors contribute to low bone mineral density in such patients. Muscle hypotonia, low amounts of physical activity, poor calcium and vitamin D intakes, hypogonadism, growth retardation and thyroid dysfunction contribute to substantial impairments in skeletal maturation and bone-mass accrual that predispose these patients to fragility fractures. Here, we review indications and limitations of bone-mass measurements in children, summarize the endocrine and skeletal abnormalities in patients presenting with Down syndrome, and review studies that investigate therapeutic strategies for such patients.
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PMID:Endocrine and musculoskeletal abnormalities in patients with Down syndrome. 1942 Dec 41

Down syndrome (DS) is caused by trisomy of all or part of human chromosome 21 (HSA21) and is the most common genetic cause of significant intellectual disability. In addition to intellectual disability, many other health problems, such as congenital heart disease, Alzheimer's disease, leukemia, hypotonia, motor disorders, and various physical anomalies occur at an elevated frequency in people with DS. On the other hand, people with DS seem to be at a decreased risk of certain cancers and perhaps of atherosclerosis. There is wide variability in the phenotypes associated with DS. Although ultimately the phenotypes of DS must be due to trisomy of HSA21, the genetic mechanisms by which the phenotypes arise are not understood. The recent recognition that there are many genetically active elements that do not encode proteins makes the situation more complex. Additional complexity may exist due to possible epigenetic changes that may act differently in DS. Numerous mouse models with features reminiscent of those seen in individuals with DS have been produced and studied in some depth, and these have added considerable insight into possible genetic mechanisms behind some of the phenotypes. These mouse models allow experimental approaches, including attempts at therapy, that are not possible in humans. Progress in understanding the genetic mechanisms by which trisomy of HSA21 leads to DS is the subject of this review.
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PMID:Molecular genetic analysis of Down syndrome. 1952 51

The inherent joint laxity and muscle hypotonia of adults with Down syndrome (DS) may result in reduced gait stability and increased energetic cost. These factors vary as a function of walking speed and may be reflected in gait patterns. The present study therefore examined whether the three-dimensional motion of the body center of mass (COM) and stepping characteristics differ between adults with and without DS as a function of speed. Fifteen adults with DS and 15 adults without DS underwent a series of treadmill walking trials. Walking speeds were determined as Froude numbers, based on leg length. Participants walked at Froude numbers of 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, and, for adults without DS, 0.7. Whole-body kinematic data were collected for 30-35 steps at each speed. Across speeds, adults with DS showed greater and more variable mediolateral COM motion than adults without DS. COM anteroposterior velocity and vertical motion did not differ in range between groups, but were more variable in adults with DS. Adults with DS also showed smaller-duration steps and varied their step widths and step lengths more than adults without DS. The results suggest a gait pattern with lesser stability and greater energetic cost among adults with DS.
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PMID:Effects of Down syndrome on three-dimensional motion during walking at different speeds. 1959 93

We compared the frequency of phenotypic features of 40 children with Down syndrome between individuals with a maternally or paternally derived extra chromosome 21, using quantitative FISH for comparing heteromorphisms of the nucleolar organizing region. Parental origin was determined in 90% of families. Hypotonia and craniofacial abnormalities were present in 90% or more individuals, irrespective of parental origin of chromosome 21. Congenital heart defects were more frequent in cases with a maternally derived extra chromosome 21. Imprinted gene(s) may contribute to the development of congenital heart defects in Down syndrome.
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PMID:Phenotypic heterogeneity and parental origin of extra chromosome 21 in Down syndrome. 1967 44

An 8-month-old boy was admitted to the hospital because of recurrent bronchopneumonia and gastrointestinal tract infections. On physical examination, he had hypotonia, mental retardation, microcephaly with flat facies, low nasal bridge, small nose, small ears. Laboratory evaluation revealed Down syndrome, lymphopenia, hypogammaglobulinemia, reduced proportions of the peripheral blood lymphocytes with an inverted CD4/CD8 ratio and markedly reduced mitogen response of the lymphocytes. We report here unique case of Down syndrome associated with severe combined immunodeficiency.
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PMID:Down syndrome associated with severe combined immunodeficiency: a case report. 1985 34

Speech production in young people with Down's syndrome has been found to be variable and inconsistent. Errors tend to be more in the production of sounds that typically develop later, for example, fricatives and affricates, rather than stops and nasals. It has been suggested that inconsistency in production is a result of a motor speech deficit. Late acquired fricatives such as /s/ and /integral/ are complex articulations, which may require more precise motor programming and may therefore show highly inconsistent productions. Other factors potentially affecting speech production in this population are abnormal palatal structure, hearing loss, and hypotonia. A group of 20 young people with Down's syndrome were recorded using Electropalatography (EPG), reading a wordlist containing the phrase 'a sheep'. The wordlist contained seven other phrases and was repeated 10 times. Eight typically developing, cognitively matched children and eight adults were also recorded producing the same data set. Articulatory (EPG pattern analysis) and perceptual analyses of the 10 productions of /integral/ were carried out. /integral/ production was found to be inconsistent in the young people with Down's syndrome, with more errors both in the auditory analysis and articulatory analysis than in the typical sample, which may be due to a motor programming or motor control problem. There were a greater number of errors in the EPG analysis than in the perceptual analysis. This suggests that some young people with DS were able to produce perceptually acceptable /integral/ with atypical EPG patterns. The use of typical, adult-modelled /integral/ EPG patterns in therapy may be inappropriate for some children with DS who present with atypical palatal structures.
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PMID:A perceptual and electropalatographic study of /integral/ in young people with Down's syndrome. 2000 7


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