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)

A white Italian boy, aged 5 years and 8 months, is reported with failure to thrive, hypotonia, truncal ataxia, psychomotor retardation, and congenital horizontal pendular nystagmus with only waves I and II on auditory brainstem responses. Our patient's clinical picture resembles that previously reported in 10 male Oriental patients. He did not manifest spastic diplegia by the age of 2 years, as did the subjects reported in the literature, but knee-jerk hyperreflexia was evident at the most recent clinical reevaluation. Serial brain MRI studies revealed a cystic brain lesion and peritrigonal hyperintensities with no brainstem abnormalities. To date, no other child with a similar syndrome has been described either in Europe or in America. The clinical features of this condition are consistent and characteristic. A definitive diagnosis is achieved by demonstrating the absence of all waves following wave I or wave II on auditory brainstem responses as early as 3 months of age. Due to the predominance of males, the occurrence in siblings, the early age at onset, the non-progressive course, and the characteristic auditory brainstem response findings, the syndrome may have a genetic origin and be attributable to a dysgenetic brainstem lesion.
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PMID:Hypotonia, congenital nystagmus, ataxia, and abnormal auditory brainstem responses: a report on the first white patient. 1006 51

We report on four children of both sexes from a highly inbred family with hypotonia, spastic diplegia, microcephaly, microphthalmia, congenital cataract, optic atrophy, ptosis, kyphoscoliosis, short stature, severe mental retardation, and cerebral malformations. Six other children may also have been affected. The differential diagnosis and the possibility of a second family with the micro syndrome are discussed.
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PMID:Microcephaly, microphthalmia, congenital cataract, optic atrophy, short stature, hypotonia, severe psychomotor retardation, and cerebral malformations: a second family with micro syndrome or a new syndrome? 1046 17

To study the phenotypic spectrum and management of holoprosencephaly (HPE), we reviewed the findings of eight children with HPE from 3 to 10 years of age, who underwent intervention programs and rehabilitation at our center. One patient had alobar HPE, three semilobar HPE, and four lobar HPE. All patients had postnatal growth retardation, and seven showed a decreased BMI (< 25% tile). All patients had severe developmental delay and mental retardation (DQ < 40), showing no obvious correlation between their severity and the type of HPE. Neurologically seven patients had spasticity (3 spastic quadriplegia, 2 spastic diplegia, 2 mixed-type), except one patient with a 7q deletion [46,XY,del(7) (q35)] who had generalized hypotonia. Seven had variable types of seizures. All patients had feeding difficulties and were assessed by speech-language therapists. Four patients required tube feeding, four had gastroesophageal reflux disease. Recurrent respiratory tract infection was common. Three patients had abnormal serum sodium concentration (1 diabetes insipidus, 1 idiopathic hypernatremia, 1 hyponatremia). No family history of HPE was elicited. In conclusion, patients with HPE should be followed up closely for complications such as feeding difficulty, malnutrition, seizures, spasticity, infection, and osmoreceptor-hypothalamus-hypophyseal axis abnormalities.
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PMID:[Clinical spectrum and management of holoprosencephaly]. 1091 68

Congenital hypothyroidism (CH) is the commonest treatable cause of mental retardation. The prevelance is 1/3000 - 1/4000 live births worldwide. The importance of CH is that, the longer the diagnosis of CH is delayed, the higher the risk of mental retardation and neurologic sequale; such as poor motor coordination, ataxia, spastic diplegia, muscular hypotonia, strabismus, learning disability and diminished attention span. The most common cause of permenant CH is thyroid dysgenesis (85-90%) in which the transcription factors TTF1,TTF2 and PAX8 would appear to be obvious candidate genes in the aetiology. Especially cardiac defects and some other birth defects are described in patients with CH. Inborn errors of thyroid hormonogenesis are responsible for 10-15% of CH cases and usually have autosomal recessive inheritance, consistent with a single gene mutation. Transient CH is very common in prematures with an estimate of 10% of CH babies identified on newborn screening, or 1 in 40,000 neonates. CH neonates are usually symptom-free and the most encountered symptoms are prolonged jaundice, large fontanelles and umbilical hernia. In general, the extent of clinical findings depends on the cause, severity and duration of hypothyroidism. An elevated TSH>20 microm Iu/L and a decreased concentration of T4 confirms the diagnosis of CH. Infants with permanant abnormalities of thyroid function mostly have a serum TSH concentration > 50 microm Iu/L. Ultrasonography, thyroid scintigraphy, bone x ray of the knee and serum thyroglobulin concentration are the other essentials after diagnosis to clarify the status of the thyroid and the severity of hypothyroidism. The higher doses of 10- 15 microm g/kg/day and the commencement of treatment before 2 weeks gave rise to better long term outcome of CH patients. In the follow up of the patients noncompliance is the most important problem and serum freeT4 or T4 and TSH should be obtained at each visit to adjust the doses of L-thyroxine. Still a small number of patients with severe hypothyroidism in utero or reflected by clinical signs and symptoms extremely low T4 levels and delayed bone age may have intellectual deficits despite normal intelligence.
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PMID:Congenital hypothyroidism clinical aspects and late consequences. 1644 57

We describe 3 patients with bilateral operculum syndrome. They presented with various degrees of suprabulbar (pseudobulbar) signs in addition to delay in cognitive, motor, and speech development in 2 children and developmental language disorder in the third one. A patient with schizencephaly in the left perisylvian area and contralateral polymicrogyria had spastic hemiparesis on the right side, whereas another patient showed bilateral underdevelopment of the opercula in association with axial hypotonia and spastic diplegia. Both of them had epileptiform discharges on the electroencephalogram without clinical manifestations of seizures. The magnetic resonance imaging of the third child with developmental language disorder was normal; however, his electroencephalogram showed frequent bilateral subclinical centrotemporal epileptiform discharges, probably responsible for the speech delay. Structural or functional involvement of the opercula bilaterally was a common finding in all the 3 patients and they had symptoms similar to those described in the developmental type of Foix-Chavany-Marie and Worster-Drought syndromes.
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PMID:Bilateral operculum syndrome in childhood. 1919 75

Warburg Micro Syndrome is a rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. We have found five new mutations in the RAB3GAP1 gene in seven patients with suspected Micro Syndrome from families with Turkish, Palestinian, Danish, and Guatemalan backgrounds. A thorough clinical investigation of the patients has allowed the delineation of symptoms that are consistently present in the patients and may aid the differential diagnosis of Micro Syndrome for patients in the future. All patients had postnatal microcephaly, micropthalmia, microcornia, bilateral congenital cataracts, short palpebral fissures, optic atrophy, severe mental retardation, and congenital hypotonia with subsequent spasticity. Only one patient had microcephaly at birth, highlighting the fact that congenital microcephaly is not a consistent feature of Micro syndrome. Analysis of the brain magnetic resonance imagings (MRIs) revealed a consistent pattern of polymicrogyria in the frontal and parietal lobes, wide sylvian fissures, a thin hypoplastic corpus callosum, and increased subdural spaces. All patients were homozygous for the mutations detected and all mutations were predicted to result in a truncated RAB3GAP1 protein. The analysis of nine polymorphic markers flanking the RAB3GAP1 gene showed that the mutation c.1410C>A (p.Tyr470X), for which a Danish patient was homozygous, occurred on a haplotype that is shared by the unrelated heterozygous parents of the patient. This suggests a possible founder effect for this mutation in the Danish population.
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PMID:New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish. 2051 59

Canavan disease is a rare autosomal recessive leukodystrophy characterized by abnormal accumulation of N-acetyl aspartate (NAA) in brain white matter. Currently, there is no cure for this disease, and management of patients consists mainly of treating symptoms. We describe a 3-month-old girl who was hospitalized for poor head control and decreased muscle tone. A battery of laboratory and genetic (homozygous mutation p.C218X) analysis revealed the presence of Canavan disease. Lithium citrate was initiated at a dosage of 45 mg/kg per day after diagnosis. Periodic controls of thyroid and liver function, and lithium levels in blood showed that this drug was sure and well tolerated. After 1 year of treatment, NAA levels decreased by approximately 20% in the brain region, urinary NAA levels showed a reduction of 80%, and patient improved alertness and visual tracking but continued with no heat support, axial hypotonia, and spastic diplegia. In our patient, the results obtained after drug administration are important with respect to the decrease in NAA and more discreet in clinical improvement. However, given the absence of adverse effects and limited treatment options, lithium citrate may be a good alternative to stop the progression of the disease and improve the quality of life of patients.
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PMID:Lithium citrate as treatment of Canavan disease. 2259 12

The objectives of this study were to determine prognostic predictors for ambulation among Thai children with cerebral palsy and identify their ambulatory status. A retrospective cohort study was performed at 6 special schools or hospitals for children with physical disabilities. The prognostic predictors for ambulation were analyzed by multivariable ordinal continuation ratio logistic regression. The 533 participants aged 2 to 18 years were divided into 3 groups: 186 with independent ambulation (Gross Motor Function Classification System [GMFCS I-II]), 71 with assisted ambulation (Gross Motor Function Classification System III), and 276 with nonambulation (Gross Motor Function Classification System IV-V). The significant positive predictors for ambulation were type of cerebral palsy (spastic diplegia, spastic hemiplegia, dyskinesia, ataxia, hypotonia, and mixed type), sitting independently at age 2 years, and eating independently. These predictors were used to develop clinical scoring for predicting the future ability to walk among Thai children with cerebral palsy.
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PMID:Prognostic Predictors for Ambulation in Thai Children With Cerebral Palsy Aged 2 to 18 Years. 2592 62

Nonketotic hyperglycinemia (NKH) is an autosomal recessive hereditary disease caused by a defect in the glycine cleavage system and is classified into typical and atypical NKH. Atypical NKH has complex manifestations and is difficult to diagnose in clinical practice. This article reports a family of NKH. The parents had normal phenotypes, and the older brother and the younger sister developed this disease in the neonatal period. The older brother manifested as intractable epilepsy, severe spastic diplegia, intellectual disability, an increased level of glycine in blood and cerebrospinal fluid, an increased glycine/creatinine ratio in urine, and an increased ratio of glycine concentration in cerebrospinal fluid and blood. The younger sister manifested as delayed language development, ataxia, chorea, mental and behavior disorders induced by pyrexia, hypotonia, an increased level of glycine in cerebrospinal fluid, and an increased ratio of glycine concentration in cerebrospinal fluid and blood. High-throughput sequencing found a maternal missense mutation, c.3006C>G (p.C1002W), and a paternal nonsense mutation, c.1256C>G (p.S419X), in the GLDC gene in both patients. These two mutations were thought to be pathogenic mutations by a biological software. H293T cells transfected with these two mutants of the GLDC gene had a down-regulated activity of glycine decarboxylase. NKH has various phenotypes, and high-throughput sequencing helps to make a confirmed diagnosis. Atypical NKH is associated with the downregulated activity of glycine decarboxylase caused by gene mutations.
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PMID:[Clinical and genetic analyses of a family with atypical nonketotic hyperglycinemia caused by compound heterozygous mutations in the GLDC gene]. 2904 6

Deletions in the 12q21 region are rare and non-recurrent CNVs. To date, only 11 patients with deletions in this region have been reported in the literature. These patients most often presented with syndromic intellectual deficiency, ventriculomegaly or hydrocephalus, ectodermal abnormalities, growth retardation and renal and cardiac malformations, suggesting a recognizable microdeletion syndrome. We report three new patients with overlapping deletions of the 12q21 region, including the smallest deletion reported to date and the first case characterized by array CGH during pregnancy. We describe specific clinical findings and shared facial features as developmental delay, ectodermal abnormalities, ventriculomegaly or hydrocephalus, axial hypotonia or spastic diplegia, growth retardation, heart defect, hydronephrosis, ureteral reflux or horseshoe kidney, large thorax or pectus excavatum, syndactyly of 2-3 toes, pterygium coli or excess nuchal skin, large anterior fontanel, low set ears, prominent forehead, short-upturned nose with nostril hypoplasia, microretrognathia and hypertelorism. These new patients and a comprehensive review of the literature allow us to define a minimum critical region spanning 1.6 Mb in 12q21. By screening the critical region using prediction tools, we identified two candidate genes: SYT1and PPP1R12A.
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PMID:12q21 deletion syndrome: Narrowing the critical region down to 1.6 Mb including SYT1 and PPP1R12A. 3263 79


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