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ABSTRACT: : To describe hypermobility, balance, pain, activity, and participation in children with hypermobility and compare these characteristics with those of a control group.
: Twenty children aged 8 to 16 years with hypermobility syndrome (HMS) or Ehlers-Danlos syndrome and a control group of 24 children of the same age participated in the study. Hypermobility was assessed according to the Del Mar scale, balance was assessed with the Bruininks-Oseretsky test of motor proficiency, and participation in daily life activities was assessed with the frequency of participation questionnaire. Pain and physical activity were assessed in a diary.
: In comparison with the control group, the children with hypermobility had significantly more hypermobile joints and more pain and scored lower in the balance test, and their activity was affected on a daily basis.
: Pain appears to affect activity and participation in children with HMS. Balance is decreased in children with HMS compared with healthy controls.
Pediatric physical therapy: the official publication of the Section on Pediatrics of the American Physical Therapy Association 01/2012; 24(4):339-44.
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ABSTRACT: To investigate the prevalence, co-morbidities and aetiologies of severe mental retardation (SMR) in a cohort of Swedish children and to further penetrate aetiologies in the group with undetermined causes by application of updated clinical-genetic methods.
The study was population-based and included children living in the County of Halland in western Sweden in 2004 (born 1987-1998; 46,000 children). Patients were identified through habilitation centres, paediatric clinics and school health services. Patients with unclear prenatal aetiology were investigated with single nucleotide polymorphism (SNP)-array.
Severe mental retardation was identified in 133 children from 132 families, corresponding to a prevalence of 2.9 per 1000 children. There were more males than females (90:43).The aetiology was prenatal in 82 (62%), perinatal in 14 (10%) and postnatal in 8 (6%). In 29 (22 %) children, mainly males with autism, the cause could not be related to the time of birth. In the prenatal group, genetic causes dominated, but still 23 children remained undiagnosed; in 5/19 of these patients, a diagnosis could be made after SNP-array analysis. One or more associated neurological handicaps were found in more than half of the children.
Prevalence and co-morbidity were similar to previous Scandinavian studies. High-resolution chromosomal micro-array techniques are valuable diagnostic tools, reducing the number of patients with unexplained SMR.
Acta Paediatrica 07/2011; 101(1):85-91. · 2.07 Impact Factor
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Stefan Kölker,
Ernst Christensen,
James V Leonard,
Cheryl R Greenberg,
Avihu Boneh,
Alberto B Burlina,
Alessandro P Burlina,
Marjorie Dixon,
Marinus Duran,
Angels García Cazorla,
Stephen I Goodman,
David M Koeller, Mårten Kyllerman,
Chris Mühlhausen,
Edith Müller,
Jürgen G Okun,
Bridget Wilcken,
Georg F Hoffmann,
Peter Burgard
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ABSTRACT: Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. The neuropathological correlate is striatal injury which results from encephalopathic crises precipitated by infectious diseases, immunizations and surgery during a finite period of brain development, or develops insidiously without clinically apparent crises. Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and L-tryptophan. This defect gives rise to elevated glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine which can be detected by gas chromatography/mass spectrometry (organic acids) or tandem mass spectrometry (acylcarnitines). Glutaric aciduria type I is included in the panel of diseases that are identified by expanded newborn screening in some countries. It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. However, initiation of treatment after the onset of symptoms is generally not effective in preventing permanent damage. Secondary dystonia is often difficult to treat, and the efficacy of available drugs cannot be predicted precisely in individual patients. The major aim of this revision is to re-evaluate the previous diagnostic and therapeutic recommendations for patients with this disease and incorporate new research findings into the guideline.
Journal of Inherited Metabolic Disease 03/2011; 34(3):677-94. · 3.58 Impact Factor
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ABSTRACT: We reviewed the medical history, EEG recordings, and developmental milestones of 19 children with speech and language dysfunction and focal epileptiform activity. Speech, language, and neuropsychological assessments and EEG recordings were performed at follow-up, and prognostic indicators were analyzed. Three patterns of language development were observed: late start and slow development, late start and deterioration/regression, and normal start and later regression/deterioration. No differences in test results among these groups were seen, indicating a spectrum of related conditions including Landau-Kleffner syndrome and epileptic language disorder. More than half of the participants had speech and language dysfunction at follow-up. IQ levels, working memory, and processing speed were also affected. Dysfunction of auditory perception in noise was found in more than half of the participants, and dysfunction of auditory attention in all. Dysfunction of communication, oral motor ability, and stuttering were noted in a few. Family history of seizures and abundant epileptiform activity indicated a worse prognosis.
Epilepsy & Behavior 07/2010; 18(3):267-75. · 2.34 Impact Factor
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Hanna Orlén,
Atle Melberg,
Raili Raininko,
Eva Kumlien,
Miriam Entesarian,
Per Söderberg,
Magnus Påhlman,
Niklas Darin, Mårten Kyllerman,
Eva Holmberg,
Henry Engler,
Urban Eriksson,
Niklas Dahl
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ABSTRACT: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes. Disease onset is during the first three decades of life with spastic paraplegia and mental impairment. Peripheral neuropathy and amyotrophy may occur. Kjellin syndrome is characterized by central retinal degeneration in addition to ARHSP-TCC and the disease is associated with mutations in the SPG15 gene. We identified five patients in four unrelated kindreds with spastic paraplegia and mental impairment. Magnetic resonance imaging revealed TCC, atrophy elsewhere in the brain and increased T2 signal intensity in the periventricular white matter. Probands from the four kindreds were screened for mutations in the SPG11 gene. All patients were found homozygous or compound heterozygous for truncating SPG11 mutations of which four are reported for the first time. Ophthalmological investigations revealed that the four index cases have central retinal degeneration consistent with Kjellin syndrome. PET examinations with N-[11C-methyl]-L-deuterodeprenyl (DED) and fluor-18 2-fluorodeoxyglucose (FDG) were performed in two patients with Kjellin syndrome. We observed a reduced glucose uptake in the thalami, anterior cingulum, and sensorimotor cortex indicating neuronal loss, and an increased DED binding in the thalami and pons which suggests astrogliosis. From our results we extend the SPG11 associated phenotype to comprise also Kjellin syndrome, previously found to be associated with mutations in the SPG15 gene. We anticipate that degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2009; 150B(7):984-92. · 3.70 Impact Factor
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ABSTRACT: Galactosialidosis (MIM 256540) is an autosomal recessive lysosomal storage disease caused by a defect of the protective protein/cathepsin A. Increased amounts of urinary sialic acid-rich oligosaccharides are considered to be an essential diagnostic marker of the disease. We here report a patient with atypical clinical features who consistently has excreted normal amounts of sialyloligosaccharides in the urine. The boy started to have attacks of neuropathic pain associated with hyperesthesia around 1(1/2) years of age. From 4 years of age when his vision was first tested, the patient developed progressive visual loss and at the age of 10 years, macular cherry-red spots were found. At this age, he also had a mild learning disability and clinical examination showed mild facial coarsening, increased lumbar lordosis and pyramidal signs in the legs. In conclusion, the clinical and laboratory features of this patient show that galactosialidosis may be considered in patients even in the absence of oligosacchariduria and that galactosialidosis should be regarded as a differential diagnosis in patients with neuropathic pain.
European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 01/2009; 13(6):553-5. · 2.01 Impact Factor
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Gregor D Gilfillan,
Kaja K Selmer,
Ingrid Roxrud,
Raffaella Smith, Mårten Kyllerman,
Kristin Eiklid,
Mette Kroken,
Morten Mattingsdal,
Thore Egeland,
Harald Stenmark, [......],
P Andrew Futreal,
Jon Teague,
Sarah Edkins,
Jozef Gecz,
Gillian Turner,
F Lucy Raymond,
Charles Schwartz,
Roger E Stevenson,
Dag E Undlien,
Petter Strømme
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ABSTRACT: Linkage analysis and DNA sequencing in a family exhibiting an X-linked mental retardation (XLMR) syndrome, characterized by microcephaly, epilepsy, ataxia, and absent speech and resembling Angelman syndrome, identified a deletion in the SLC9A6 gene encoding the Na(+)/H(+) exchanger NHE6. Subsequently, other mutations were found in a male with mental retardation (MR) who had been investigated for Angelman syndrome and in two XLMR families with epilepsy and ataxia, including the family designated as having Christianson syndrome. Therefore, mutations in SLC9A6 cause X-linked mental retardation. Additionally, males with findings suggestive of unexplained Angelman syndrome should be considered as potential candidates for SLC9A6 mutations.
The American Journal of Human Genetics 05/2008; 82(4):1003-10. · 10.60 Impact Factor
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ABSTRACT: We recently described a new autosomal dominant myopathy associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene (MYH2). In this study, we performed mutation analysis of MYH2 in eight Swedish patients with familial myopathy of unknown cause. In two of the eight index cases, we identified novel heterozygous missense mutations in MYH2, one in each case: V970I and L1061V. The mutations were located in subfragment 2 of the MyHC and they changed highly conserved residues. Most family members carrying the mutations had signs and symptoms consisting mainly of mild muscle weakness and myalgia. In addition, we analyzed the extent and distribution of nucleotide variation in MYH2 in 50 blood donors, who served as controls, by the complete sequencing of all 38 exons comprising the coding region. We identified only six polymorphic sites, five of which were synonymous polymorphisms. One variant, which occurred at an allele frequency of 0.01, was identical to the L1061V that was also found in one of the families with myopathy. The results of the analysis of normal variation indicate that there is strong selective pressure against mutations in MYH2. On the basis of these results, we suggest that MyHC genes should be regarded as candidate genes in cases of hereditary myopathies of unknown etiology.
European Journal of HumanGenetics 06/2005; 13(5):617-22. · 4.40 Impact Factor
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ABSTRACT: To explore possible patterns of comorbidity in children with severe developmental language disorders (DLD).
A retrospective investigation of the clinical records of 28 children relating to oral motor and language problems, psychological profiles, medical history and EEG findings.
36% of all the children had pure expressive language problems, 64% had combined expressive-receptive language problems and 57% had additional oral motor problems. Girls predominated in expressive-receptive problems, while boys predominated in oral motor problems. Children with expressive-receptive disorders were over-represented at the lower end of normal full-scale IQ (p = 0.015). Lower verbal than non-verbal IQ levels were almost as common as equal levels, but a lower non-verbal IQ than verbal IQ was also found. Pre/perinatal problems were found in 21%, and heredity for developmental language problems or dyslexia in 39%. There was a higher proportion of attention and motor problems, EEG abnormalities, and epileptic syndromes than in the general population (p < 0.001).
In severe DLD, both pure expressive and mixed expressive-receptive problems are found, and oral motor problems are common. Gender differences regarding symptoms are present. Receptive language ability is associated with the full-scale IQ level. A high proportion of EEG abnormalities and epilepsy is found. There is a complex pattern of comorbidity between speech-language symptoms, psychological characteristics, heredity and EEG findings.
Acta Paediatrica 05/2005; 94(4):471-8. · 2.07 Impact Factor
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Developmental Medicine & Child Neurology 01/2005; 47(02):143 - 143. · 2.92 Impact Factor
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ABSTRACT: The aim of this study was to examine the character of motor dysfunction in individuals with Angelman syndrome (AS). Thirty-three children and adolescents (median age 6 years, range 18 months to 23 years) were consecutively investigated for learning disability, epilepsy, and motor dysfunction to detect suspected AS. Twenty-three individuals (13 males, 10 females; median age 5 years 6 months, range 21 months to 23 years) fulfilled international consensus criteria for AS. Clinical diagnosis was supported by a positive DNA methylation test in eleven participants. Ten participants (seven males, three females; median age six years, range 18 months to 13 years) did not comply with consensus criteria for AS and were regarded as a comparison group. There was no significant difference between the AS and the comparison group regarding age or developmental level. Median developmental quotient level was 26 months (range 8 to 63 months); median gross motor developmental level in participants with AS was 24 months (range 8 to 60 months); median fine motor developmental level was 15 months (range 6 to 60 months). Muscle strength, spasticity, tremor, and coactivation were assessed: distal lower limb spasticity, ataxic like gait, stiff lower limbs, and the presence of coactivation during locomotion were significantly more frequent in participants with AS than in the comparison group (p<0.05). Asymmetry of muscle strength and spasticity were frequent. Neurological abnormalities were insufficient for a diagnosis of cerebral palsy and impeded function less than immaturity in both AS groups. Risk of increasing impairment needs to be anticipated to prevent negative long-term effects of muscle imbalance and motor asymmetries in individuals with AS.
Developmental Medicine & Child Neurology 04/2004; 46(4):239-43. · 2.92 Impact Factor
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ABSTRACT: We recently described a new autosomal dominant myopathy (OMIM #605637) associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene ( MYH2), which encodes for the fast myosin isoform that is expressed in type 2A muscle fibers. There was a correlation between muscle pathology and expression of MyHC IIa. Low expression of the mutation was associated with a milder phenotype. Since physical activity influences MyHC isoform expression in normal individuals, we investigated whether endurance training can alter the expression of MyHC isoforms in patients with the MYH2 mutation. The expression of MyHC I, IIa and IIx was analysed in muscle specimens from six patients before and after an eight-week endurancetraining program by SDS-polyacrylamide gel electrophoresis and immuno-histochemistry. There was a clear and consistent shift from fast to slow MyHC isoform expression, but the training program did not result in the desired reduction of MyHC IIa, which may be due to the limited time period of training. Fiber type transition was further illustrated by the appearance of hybrid muscle fibers expressing more than one MyHC isoform after the training period. All patients showed an increase in maximal workload but no significant change in isometric muscle strength.We conclude that endurance training in patients with myosin myopathy may be an important way to alter the expression of defective MyHC isoforms.
Journal of Neurology 03/2004; 251(2):179-83. · 3.47 Impact Factor
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ABSTRACT: All 28 patients, 13 females and 15 males, with glutaric aciduria type 1 diagnosed between 1975 and 2001 in Denmark, Finland, Norway and Sweden were identified and studied retrospectively until 2001. Mass screening was not performed. Three were sibling cases. Prenatal enzymatic diagnosis performed in 11 pregnancies led to termination in one. The median follow-up time was 14 years. Six patients had died. At 10 years of age the cumulative survival rate was 89% and at 35 years 44%. The dominating neurological sign was dystonia in 20 and dyskinesia in 4. Three had only slight spastic signs and information was missing in one. The head circumference at birth was significantly larger than normal and increased significantly until 6 months of age. The onset was acute encephalopathic in 24 patients and insidious in 3. From the time of diagnosis, all patients but one were prescribed protein restriction and/or a diet low in lysine and tryptophan. Riboflavine and/or carnitine supplementation were given to 25. Neurological deficits did not improve on the offered treatment. Deterioration may have been averted by intense acute metabolic treatment in a few patients. Dystonia correlated significantly to absence of speech but not to cognitive function. Severe disability, including motor, cognitive and speech functions, correlated significantly with acute onset, dystonia and mortality, and weakly with a deteriorating course, but not with age at onset, diagnosis, or follow-up, nor to head size. Results from future population studies derived from mass screening will have to relate to clinical diagnostic series of the kind presented here.
European Journal of Paediatric Neurology 02/2004; 8(3):121-9. · 2.12 Impact Factor
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ABSTRACT: A 25-year-old MECP2-mutated female with odd developmental and dyspraxic/ataxic features, followed up through two decades, is reported. She does not fit either the classical Rett syndrome or the criteria required for any Rett variant phenotypes so far described. Nevertheless, she belongs clinically to the latter group. This case deserves attention in order, among other things, to provide important clues to better understand the puzzling battery of neuroimpairments and behavioural abnormalities met in classical Rett phenotypes and Rett variants defined thus far.
European Journal of Paediatric Neurology 02/2003; 7(6):417-21. · 2.12 Impact Factor
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ABSTRACT: Mutations in the methyl-CpG-binding protein-2 (MECP2) gene on Xq28 have been found to be a cause of Rett syndrome (RS). In a previous mutation screening, we found MECP2 mutations in 81% of Swedish classical Rett women. In this study, we have analyzed 22 patients for MECP2 deletions using multiplex-ligation-dependent probe amplification (MLPA). Clinically, 11 of the patients who were classical Rett women, 3 were forme fruste, 1 was congenital RS, and 7 were Rett variants. As inclusion criteria, we used DNA from patients in whom previous sequencing results showed no mutations in coding portions of the MECP2 gene. MLPA is a method based on multiplex PCR. In one PCR, as many as 40 probes are amplified with the same primers. The specificity of the amplification products is determined by the site-specific hybridization of each probe construct, prior to amplification. Each PCR product has a unique length, which makes it possible to identify it by size separation. In 3 of 11 (27%) classical Rett women, we detected large deletions in MECP2 using MLPA. All these patients had deletions covering two exons; in 2 cases the deletion involved exons 3 and 4 and, in one case, exons 1 and 2 were missing. In the forme fruste, congenital and Rett-variant patients, we found no large deletions. We have found that MLPA is useful when it comes to finding large deletions compromising whole exons in MECP2. Used as a complementary method to DNA sequencing, it revealed new MECP2 mutations in classical RS patients.
Genetic Testing 02/2003; 7(4):329-32. · 1.17 Impact Factor
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ABSTRACT: A screening for submicroscopic rearrangements was performed in 111 patients with idiopathic mental retardation (MR) using fluorescence in situ hybridization (FISH) probes from the subtelomeric regions of all chromosome arms. Ten cryptic rearrangements were found (9%): five de novo deletions; one unbalanced de novo translocation; three unbalanced inherited translocations; and one unbalanced recombinant chromosome, inherited from a parent with a pericentric inversion. In addition, 50 of the patients were screened for interstitial rearrangements with spectral karyotyping (SKY), but no aberrations were found. However, SKY detected the subtelomeric rearrangement in three of the four unbalanced translocations. Dysmorphic features were present in all patients with detected subtelomeric rearrangements.
American Journal of Medical Genetics 03/2002; 107(4):275-84.
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ABSTRACT: We have recently described an autosomal dominant hereditary inclusion body myopathy (h-IBM). Clinically it is is characterized
by congenital joint contractures and slowly progressive, proximal muscle weakness and ophthalmoplegia. There is deterioration
of muscle function between 30 and 50 years of age. While young patients show minor pathological changes in muscle, the middle-aged
and old patients show rimmed vacuoles and inclusions of filaments measuring 15–18 nm in diameter. Except for the absence of
significant inflammation the histopathology is similar to that found in sporadic inclusion body myositis (s-IBM). In s-IBM
mitochondrial alterations including cytochrome c oxidase (COX) -deficient muscle fibers are common. These are due to multiple mitochondrial DNA (mtDNA) deletions. In this
study we investigated the occurrence of mitochondrial alterations in autosomal dominant h-IBM. Young affected individuals
showed no mitochondrial changes but three patients aged 38, 51 and 59 years, respectively, showed ragged red fibers and COX-deficient
muscle fibers. Polymerase chain reaction analysis showed multiple mtDNA deletions. By in situ hybridization clonal expansions
of mtDNA with deletions were demonstrated in COX-deficient muscle fibers. Most of the analyzed deletion breakpoints showed
nucleotide repeats flanking the deletions. The results show that COX-deficient muscle fibers and somatic mtDNA deletions are
present in this family with h-IBM. The same factors may be involved in the development of mtDNA deletions in s-IBM and this
family with h-IBM.
Acta Neuropathologica 01/2000; 100(1):23-28. · 9.32 Impact Factor
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ABSTRACT: Two families with the congenital X-linked infantile form of myotubular myopathy have been investigated by linkage analysis using markers from the X-chromosome. Linkage was found at the locus Xq28 (with DXS52). The analysis gave a peak lod score of 2.41 at the recombination fraction zero. Free recombinations (θ=0.50) were seen using the markers DXS84, DXS14 and DXS146 from the p arm of the X-chromosome. Since the disorder is very rare, it is important to add cumulative linkage data from the few families that do exist.
Clinical Genetics 04/1990; 37(5):335 - 340. · 3.13 Impact Factor
