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)

The 18q- syndrome is one of the commonest deletion syndromes. Clinical characteristics are variable but may include: hypotonia, tapered digits, "carp-like" mouth, mental retardation, and hearing impairment. Growth failure (GF; both weight and height < 3%) was reported in 80% of affected individuals. We evaluated growth hormone (GH) sufficiency in 5 18q- syndrome patients, 3 of whom had growth failure (< 3% weight and height); the remaining 2 had normal growth parameters. Laboratory evaluation of growth included measurement of IGF-1, IGFBP-3, bone ages and GH response to pituitary provocative agents. Three patients failed to produced adequate GH following stimulation testing. Of 3 patients with inadequate GH production, 1 had normal growth (above 3%). Only 1 of 5 patients had normal GH production and normal growth parameters. Our findings to date suggest that GH deficiency is common in individuals with the 18q- syndrome. The pathogenesis of this finding is unknown. We postulate that a gene(s) on 18q is involved in GH production.
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PMID:Growth hormone deficiency associated in the 18q deletion syndrome. 906 76

Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient's life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.
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PMID:Prader-Willi syndrome and growth hormone deficiency. 2493 97

Sepiapterin reductase (SR) deficiency is a rare autosomal recessively inherited error of tetrahydrobiopterin (BH4) biosynthesis, resulting in disturbed dopaminergic and serotonergic neurotransmission. The clinical phenotype is characterized by dopa-responsive movement disorders including muscular hypotonia, dystonia, and parkinsonism. Due to the rarity of the disease, the phenotype of SR deficiency is far from being completely understood. Here, we report a 7-year-old boy, who was referred for diagnostic evaluation of combined psychomotor retardation, spastic tetraplegia, extrapyramidal symptoms, and short stature. Due to discrepancy between motor status and mental condition, analyses of biogenic amines and pterins in CSF were performed, leading to the diagnosis of SR deficiency. The diagnosis was confirmed by a novel homozygous mutation c.530G>C; p.(Arg177Pro) in exon 2 of the SPR gene. Because of persistent short stature, systematic endocrinological investigations were initiated. Insufficient growth-hormone release in a severe hypoglycemic episode after overnight fasting confirmed growth-hormone deficiency as a cause of short stature. In addition, central hypothyroidism was present. A general hypothalamic affection could be excluded. Since dopamine is known to regulate growth-hormone excretion, IGF-1, IGF-BP3, and peripheral thyroid hormone levels were monitored under L-dopa/carbidopa supplementation. Both growth-hormone-dependent factors and thyroid function normalized under treatment. This is the first report describing growth-hormone deficiency and central hypothyroidism in SR deficiency. It extends the phenotypic spectrum of the disease and identifies dopamine depletion as cause for the endocrinological disturbances.
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PMID:Dopamine-Responsive Growth-Hormone Deficiency and Central Hypothyroidism in Sepiapterin Reductase Deficiency. 2600 22

Rett syndrome (RTT) is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions.
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PMID:MeCP2 Affects Skeletal Muscle Growth and Morphology through Non Cell-Autonomous Mechanisms. 2609 33

In the current study, we sought to determine the significance of the ghrelin system in Prader-Willi Syndrome (PWS). PWS is characterized by hypotonia and difficulty feeding in neonates and hyperphagia and obesity beginning later in childhood. Other features include low GH, neonatal hypoglycemia, hypogonadism, and accelerated mortality. Although the hyperphagia and obesity in PWS have been attributed to elevated levels of the orexigenic hormone ghrelin, this link has never been firmly established, nor have ghrelin's potentially protective actions to increase GH secretion, blood glucose, and survival been investigated in a PWS context. In the current study, we show that placing Snord116del mice modeling PWS on ghrelin-deficient or ghrelin receptor [GH secretagogue receptor (GHSR)]-deficient backgrounds does not impact their characteristically reduced body weight, lower plasma IGF-1, delayed sexual maturation, or increased mortality in the period prior to weaning. However, blood glucose was further reduced in male Snord116del pups on a ghrelin-deficient background, and percentage body weight gain and percentage fat mass were further reduced in male Snord116del pups on a GHSR-deficient background. Strikingly, 2 weeks of daily administration of the GHSR agonist HM01 to Snord116del neonates markedly improved survival, resulting in a nearly complete rescue of the excess mortality owing to loss of the paternal Snord116 gene. These data support further exploration of the therapeutic potential of GHSR agonist administration in limiting PWS mortality, especially during the period characterized by failure to thrive.
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PMID:Ghrelin Receptor Agonist Rescues Excess Neonatal Mortality in a Prader-Willi Syndrome Mouse Model. 3038 28