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)

We report the clinical findings and the diagnostic work-up of a 17-month-old girl with CDG-x. Predominant clinical signs were, besides psychomotor retardation and truncal hypotonia, stereotyped dystonic hand movements and ophthalmological abnormalities such as optic atrophy, nystagmus and strabismus. Other symptoms that are often found in patients with CDG were not present, such as seizures, microcephaly, cerebellar hypoplasia, dysmorphic features, hepatointestinal disease, coagulopathy or multiorgan involvement. Isoelectric focusing (IEF) of the patient's serum showed a marked elevation of disialotransferrin, thus confirming an IEF type 1 pattern. A generalized glycosylation defect was confirmed also by IEF of a further glycoprotein (alpha1-antitrypsin), an increased carbohydrate deficient transferrin (CDT) serum concentration and an increased CDT/transferrin ratio. All known types of CDG-I, secondary glycosylation abnormalities and variants of amino acid sequence were excluded.
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PMID:A new case of CDG-x with stereotyped dystonic hand movements and optic atrophy. 1211 27

Prader-Willi syndrome (PWS) is a genetic disease caused by a loss of paternal genes located in chromosome 15. Children affected by this syndrome often have preterm delivery; during childhood the hallmarks are: severe infantile hypotonia and feeding problems. Afterward, neurologic manifestations, endocrine signs and dysmetabolic abnormalities are usually seen together with craniofacial manifestations and musculoskeletal abnormalities. Obesity causes sleep abnormalities including sleep apnea. The case we present is of a 5 year old child (CA) scheduled for strabismus surgery. The child has a lot of typical (PWS) signs. A number of anaesthesiologic problems are associated with (PWS). Some of them relate to obesity, others to facial dysmorphism. Moreover, the syndrome may give a prolonged and exaggerated response to every sedative drug. P.W.S. is also characterized by thermoregulatory disorders. Sleep apnea occurs often. Considering all these problems, we planned a monopharmacologic anaesthesiologic procedure using sevoflurane.
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PMID:Monopharmacologic general anaesthesia with sevoflurane in paediatric patient with Prader-Willi syndrome. 1249 25

A male patient is reported with terminal 10q26 deletion, developmental retardation, special behaviour, and multiple clinical anomalies including hypotonia, short stature of postnatal onset, short webbed neck, craniofacial dysmorphism, pectus excavatum with widely spaced small nipples, cryptorchidism with scrotal hypoplasia, limb and musculoskeletal anomalies. The facial dysmorphism mainly consisted of trigonocephaly, a long, triangular and asymmetrical face, hypertelorism with pseudoepicanthus, broad nasal bridge, high-arched palate, retrognathia, low-set dysplastic auricles and, on ophthalmologic examination, strabismus, astigmatism and myopia. Some of these clinical stigmata were suggesting the diagnosis of Noonan syndrome. The extremities showed special features including shortening of proximal limbs, brachydactyly with syndactyly of toes II-III and left fingers III-IV, hypoplastic toenails and joint abnormalities. A diastasis of abdominal muscles was noted and, on X-rays a thoracic scoliosis and bilateral coxa valga were evidenced. Analyses of G- and T-banded chromosomes complemented by FISH analyses using different subtelomere probes detected a terminal 10q26 deletion. Subsequent FISH studies using different probes of the 10q26 region were performed in an attempt to closely define the breakpoint and the extent of the deletion and, thereby, to allow karyotype/phenotype comparison between this patient and a previously reported case with an apparently similar 10q26 deletion.
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PMID:Small terminal 10q26 deletion in a male patient with Noonan-like stigmata: diagnosis by cytogenetic and FISH analysis. 1255 12

Clinical and cytogenetical findings are reported and discussed on two siblings with discordant phenotypes despite having both a terminal 11q deletion and a distal 12q duplication resulting from an unbalanced segregation of a balanced translocation t(11:12)(q23:q24.1) mat. The oldest child, a girl, is the index patient. Her clinical features include intrauterine and postnatal growth retardation, fetal distress, mild hypotonia, early feeding difficulties, moderate developmental delay, especially in language acquisition, a velopharyngeal insufficiency with repeated otorhinopharyngeal infections, facial dysmorphism, heart ventricular septal defect, and abnormal hyperactive behaviour with sometimes autistic tendencies. The facial dysmorphic features notably consist of microcephaly, hypertelorism, large palpebral fissures, large eyes with alternant divergent strabismus, long eyelashes, a long and broad nasal bridge, a short "crested" nose with salient tip, a fishmouth with large spaces between teeth and flat palate, retrognathism, large ears and multiple dimples. The second affected child is a boy showing low birthweight, moderate developmental retardation with mainly no active language at 32 months, behaviour abnormalities with an autistic tendency, and no major physical anomalies apart from a slight facial hypotonia with often open mouth, dimples on the shoulders and right cryptorchidism. The authors stress the variable clinical expression of the chromosomal imbalance in this family resulting in low birthweight, developmental delay, abnormal behaviour, but different degrees of physical features and dysmorphism. The possible contribution of each of the two aneusomies to the phenotype is discussed.
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PMID:Partial monosomy 11q and trisomy 12q: variable expression in two siblings. 1287 9

We reviewed 45 children with cerebellar hypoplasia on magnetic resonance imaging to identify clinical features associated with cerebellar hypoplasia. We then studied children presenting with any likely associated clinical feature of cerebellar hypoplasia previously observed or reported. Two hundred fifty-one children, with one or more of these features, exhibited no cerebellar hypoplasia on imaging. We compared the children with cerebellar hypoplasia with those without cerebellar hypoplasia. Logistic regression and Pearson's chi(2) test were used. Of the 45 children with cerebellar hypoplasia, 39 exhibited developmental delay; 24, speech delay; 25, seizures; nine, microcephaly; 22, hypotonia; 22, ataxia and impaired coordination; four, abnormal movements (tremor or titubation); 13, hypertonia; eight, autistic features; and 18, ocular signs (nystagmus, strabismus, and abnormal ocular movements). Statistically significant clinical features of children with cerebellar hypoplasia compared with those without were development and speech delay, microcephaly, abnormal movements, ataxia and impaired coordination, autistic features, hypotonia, and ocular signs. The regression combination of speech delay, ataxia, hypotonia, autistic features, and ocular signs correctly predicted 86% of those with cerebellar hypoplasia. Main clinical features of cerebellar hypoplasia are developmental or speech delay, autistic features, ataxia, hypotonia, and ocular signs.
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PMID:Clinical spectrum associated with cerebellar hypoplasia. 1287 95

We present the case of an infant girl, born to first cousins, with a clinical phenotype consisting of microcephaly, hypotonia, strabismus and severe psychomotor retardation. Magnetic resonance imaging (MRI) showed global cerebellar atrophy involving the vermis and both hemispheres. The patient's serum transferrin levels were consistently unremarkable. Cerebellar biopsy, performed at 13 months of age, revealed heterotopic Purkinje cells in the molecular layer, but preservation of the external and internal granular layers. To our knowledge, this histological pattern of cerebellar cortical disorganization has not been described previously. The consanguinity of the parents suggests an autosomal recessive inheritance.
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PMID:Cerebellar hypoplasia with heterotopic purkinje cells in the molecular layer and preservation of the granule layers associated with severe encephalopathy. A new entity? 1291 Apr 42

Congenital Disorder of Glycosylation (CDG) type Ic is caused by mutations in ALG6. This gene encodes an alpha1,3 glucosyltransferase used for synthesis of the lipid linked oligosaccharide (LLO) precursor of the protein N-glycosylation pathway. CDG-Ic patients have moderate to severe psychomotor retardation, seizures, hypotonia, strabismus, and feeding difficulties. We previously identified a typical patient with a heterozygous point mutation, c.391T>C (p.Tyr131His) in ALG6. Using complementation analysis of ALG6-deficient yeast, we show that this alteration is as severe as the most common disease-causing mutation, c998C>T (p. Ala333Val), which occurs in over half of all known CDG-Ic patients. The frequency of c.391T>C (p.Tyr131His) in the US population, is 0.0214, suggesting that homozygotes would occur at a rate of& tilde;1:2,200. We identified one patient with typical CDG-Ic symptoms and a homozygous p.Tyr131His alteration in ALG6. However, in contrast to most CDG patients, her LLO and plasma transferrin glycosylation appeared normal. Thus, it is unclear whether c.391T>C causes CDG-Ic or contributes to the symptoms. Genotyping additional patients with CDG-like symptoms will be required to resolve this issue.
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PMID:Identification of a frequent variant in ALG6, the cause of Congenital Disorder of Glycosylation-Ic. 1451 65

The congenital muscular dystrophies (CMD) constitute a clinically and genetically heterogeneous group of autosomal recessive myopathies. Patients show congenital hypotonia, muscle weakness, and dystrophic changes on muscle biopsy. Mutations in four genes (FKT1, POMGnT1, POMT1, FKRP) encoding putative glycosyltransferases have been identified in a subset of patients characterized by a deficient glycosylation of alpha-dystroglycan on muscle biopsy. FKRP mutations account for a broad spectrum of patients with muscular dystrophy, from a severe congenital form with or without mental retardation (MDC1C) to a much milder limb-girdle muscular dystrophy (LGMD2I). We identified two novel homozygous missense FKRP mutations, one, A455D, in six unrelated Tunisian patients and the other, V405L, in an Algerian boy. The patients, between the ages of 3 and 12 years, presented with a severe form of MDC1C with calf hypertrophy and high serum creatine kinase levels. None had ever walked. Two had cardiac dysfunction and one strabismus. They all had mental retardation, microcephaly, cerebellar cysts, and hypoplasia of the vermis. White matter abnormalities were found in five, mostly when cranial magnetic resonance imaging was performed at a young age. These abnormalities were shown to regress in one patient, as has been observed in patients with Fukuyama CMD. Identification of a new microsatellite close to the FKRP gene allowed us to confirm the founder origin of the Tunisian mutation. These results strongly suggest that particular FKRP mutations in the homozygous state induce structural and clinical neurological lesions in addition to muscular dystrophy. They also relate MDC1C to other CMD with abnormal protein glycosylation and disordered brain function.
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PMID:New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities. Identification of a founder mutation in Tunisian families. 1465 96

Oligophrenin-1 (OPHN-1) gene disruption is known as responsible for so called "non-specific" X-linked mental retardation (MR) Billuart et al. [1998: Nature 392:923-926]. In order to search for a possible specific clinical and radiological profile for mutation in the OPHN-1 gene, clinical and 3D brain MRI studies were performed in the two families with a known mutation in OPHN-1 reported so far: a 19-year-old female with an X;12 balanced translocation encompassing OPHN-1, and four affected males of family MRX60 sharing a frameshift mutation in OPHN-1. Clinical data shared by affected individuals were neonatal hypotonia with motor delay but no obvious ataxia, marked strabismus, early onset complex partial seizures, and moderate to severe MR. Brain MRIs performed in three individuals exhibited a specific vermian dysgenesis including an incomplete sulcation of anterior and posterior vermis with the most prominent defect in lobules VI and VII. In addition, a non-specific cerebral cortico-subcortical atrophy was also observed. These clinical and radiological features suggest a distinct clinico-radiological syndrome. These preliminary data need to be confirmed in other families and will be helpful for further targeted mutation screening of the OPHN-1 gene in male patients with similar clinico-radiological features. In addition, OPHN-1 inactivation should be considered as a relevant model of developmental vermis disorganization, leading to a better understanding of the possible role of the cerebellum in MR.
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PMID:Specific clinical and brain MRI features in mentally retarded patients with mutations in the Oligophrenin-1 gene. 1473 83

Cohen syndrome is a rare genetic disorder caused by autosomal recessive inheritance and is characterized by the following features: mental retardation, infantile hypotonia, micrognathia, narrow and high-arched palate, microcephaly, prominent upper central incisors, poor dentition, short stature, and truncal obesity. Some patients have strabismus, myopia, optic atrophy, and total blindness. A small number of cases present with heart defects or mitral valve prolapse. Only approximately 100 cases have been reported in the world literature. The administration of general anesthesia in patients with Cohen syndrome can be a challenge because most of these patients are mentally retarded and uncooperative and have facial malformations that may make intubation difficult. We present our experience with the anesthetic management of a patient with Cohen syndrome.
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PMID:The anesthetic management of a patient with Cohen syndrome. 1533 97


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