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- Carlsson, G, et al.
(författare)
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Central nervous system involvement in severe congenital neutropenia : neurological and neuropsychological abnormalities associated with specific HAX1 mutations
- 2008
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 264:4, s. 388-400
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Homozygous mutations in the HAX1 gene were recently identified in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Our observations suggested that these patients also develop neurological and neuropsychological symptoms. METHODS: Detailed clinical studies and mutation analyses were performed in the surviving patients belonging to the Kostmann kindred and in two patients not related to this family, along with studies of HAX1 splice variant expression in normal human tissues. RESULTS: Five of six Kostmann family patients and one other patient from northern Sweden harboured homozygous HAX1 mutations (568C-->T, Q190X) and one carried a heterozygous ELA2 gene mutation. One Swedish patient of Kurdish extraction carried alternative homozygous HAX1 mutations (131G-->A, W44X). All the three patients with Q190X mutations who were alive and available for evaluation developed neurological disease with decreased cognitive function, and three of four patients who reached 10 years developed epilepsy. In contrast, the patients with the ELA2 and W44X HAX1 mutations, respectively, showed no obvious neurological abnormalities. Moreover, two alternative HAX1 splice variants were identified in normal human tissues, including the brain. Both transcripts contained exon 5, harbouring the Q190X mutation, whereas the 5' end of exon 2 containing the W44X mutation was spliced out from the second transcript. CONCLUSIONS: We describe neurological and neuropsychological abnormalities for the first time in Kostmann disease patients. These central nervous system symptoms appear to be associated with specific HAX1 mutations.
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| 2. |
- Heino, TJ, et al.
(författare)
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Intravenous pamidronate treatment improves growth in prepubertal osteogenesis imperfecta patients
- 2011
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 75:5, s. 354-361
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Pamidronate is widely used to treat pediatric patients with osteogenesis imperfecta (OI). We aimed at delineating the effects of monthly pamidronate therapy on the growth of different body segments in prepubertal OI patients. <i>Methods:</i> The study included 14 prepubertal patients (12 boys, 2 girls) with mild forms of OI (type I and IV). The mean age at treatment start was 7:8 years:months (3:7–11:0). Pamidronate was given as monthly intravenous infusions. The patients were measured 1 year before, at treatment start and 1 and 2 years after treatment start. <i>Results:</i> Height standard deviation score (SDS) and sitting height SDS significantly increased (p < 0.05) during the first year of treatment when compared to the pre-treatment year. No further improvement was detected during the second year of treatment. However, when plotted on disease-specific growth charts (untreated patients with the same OI types), height gain was significant during the first (p < 0.001) and second (p < 0.05) years of treatment. All patients increased their bone mineral density throughout the follow-up. <i>Conclusion:</i> Monthly pamidronate improves the growth of prepubertal patients with mild OI, where the most prominent growth stimulation is seen in the upper body segment.
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| 3. |
- Laurencikas, E, et al.
(författare)
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Metacarpophalangeal pattern profile analysis as a tool for early diagnosis of Turner syndrome
- 2005
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 46:4, s. 424-430
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To analyze the metacarpophalangeal pattern profile (MCPP) in a cohort of individuals with Turner syndrome (TS), and to assess its value as a tool for early diagnosis of TS. Material and Methods: Medical records and radiological material were collected of 71 patients with TS aged between 3 and 21 years. Forty‐six patients received growth hormone therapy (33–66 µg kg−1 day−1) and 14 of these were also treated with the anabolic steroid oxandrolone (1.25–3.75 mg day−1). A total of 233 frontal hand radiographs were studied and pattern profiles were calculated. Profiles of the TS patients were compared with those of 70 normal females. Mean pattern profiles were calculated for different age groups and extrapolated profiles for newborns and infants were developed. Results: Our results confirm that patients with TS have a distinct MCPP which differs significantly from that of normal individuals. A bone‐shortening gradient with increasing shortening from distal phalanges to metacarpals was demonstrated. We also showed that the MCPP in TS is a remarkably constant feature from 3 to 18 years. Pattern profiles did not differ significantly between the patients with 45,X and non‐45,X karyotype. MCPP was not affected by treatment with growth hormone of growth hormone plus oxandrolone. Discriminant analysis yielded correct classification in 88% of analyzed cases. Conclusion: TS individuals have a distinct hand pattern profile that is not age‐related. MCPP analysis can be applied at any age and may facilitate early diagnosis of TS. Our study showed that MCPP analysis is a specific and sensitive method that should be considered as a routinely used tool for early diagnosis of TS in girls with unexplained short stature.
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| 4. |
- Laurencikas, E, et al.
(författare)
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Metacarpophalangeal pattern profile analysis in Leri-Weill dyschondrosteosis
- 2005
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 46:2, s. 200-207
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To analyze the metacarpophalangeal profile (MCPP) in individuals with Leri‐Weill dyschondrosteosis (LWD) and to assess its value as a possible contributor to early diagnosis. Material and Methods: Hand profiles of 39 individuals with a diagnosis of LWD were calculated and analyzed. Discriminant analysis was applied to differentiate between LWD and normal individuals. Results: There was a distinct pattern profile in LWD. Mean pattern profile showed two bone‐shortening gradients, with increasing shortening from distal to proximal and from medial to lateral. Distal phalanx 2 was disproportionately long and second metacarpal was disproportionately short. Discriminant analysis yielded correct classification in 72% of analyzed cases. Conclusion: MCPP is not age‐related and the analysis can be applied at any age, facilitating early diagnosis of LWD. In view of its availability, low costs, and diagnostic value, MCPP analysis should be considered as a routine method in the patients of short stature where LWD is suspected.
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| 12. |
- Grigelioniene, Giedre, et al.
(författare)
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Asn540Lys mutation in fibroblast growth factor receptor 3 and phenotype in hypochondroplasia
- 2000
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 89:9, s. 1072-1076
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Tidskriftsartikel (refereegranskat)abstract
- Hypochondroplasia is characterized by a disproportionate short stature with rhizomelic shortening of the limbs. Amino acid substitutions Asn540Lys, Asn540Thr and Ile538Val in the fibroblast growth factor receptor 3 (FGFR3) are considered to cause hypochondroplasia. In this study we examined the FGFR3 gene for the previously described hypochondroplasia mutations and the phenotype of 23 probands with clinically and radiologically diagnosed hypochondroplasia. For the phenotype comparison, the patients were divided into two groups: Group 1: hypochondroplasia with Asn540Lys substitution; Group 2: hypochondroplasia with no mutations identified so far. A three-generation family negative for the known hypochondroplasia mutations was examined with polymorphic markers flanking the FGFR1, FGFR2 and FGFR3 genes. Nine (39%) of 23 probands were found to be heterozygous for the Asn540Lys substitution. The individuals positive for the Asn540Lys substitution were significantly more disproportionate than the individuals without this mutation. In this respect, a genotype-phenotype correlation was found in our patients. However, some individuals belonging to the group without mutations identified so far showed similarly abnormal proportions. Genotyping/haplotyping in the three-generation family with hypochondroplasia showed that FGFR1, FGFR2 and FGFR3 genes were not linked to the hypochondroplasia phenotype in this family, thus further confirming the genetic heterogeneity of hypochondroplasia. CONCLUSION: Individuals with hypochondroplasia heterozygous for the Asn540Lys substitution are significantly more disproportionate than individuals without this mutation. Our study further confirms the clinical and genetic heterogeneity of hypochondroplasia.
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| 16. |
- Laurencikas, E, et al.
(författare)
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Metacarpophalangeal pattern profile analysis: useful diagnostic tool for differentiating between dyschondrosteosis, Turner syndrome, and hypochondroplasia
- 2006
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 47:5, s. 518-524
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess the value of the metacarpophalangeal pattern profile (MCPP) analysis as a diagnostic tool for differentiating between patients with dyschondrosteosis, Turner syndrome, and hypochondroplasia. Material and Methods: Radiographic and clinical data from 135 patients between 1 and 51 years of age were collected and analyzed. The study included 25 patients with hypochondroplasia (HCP), 39 with dyschondrosteosis (LWD), and 71 with Turner syndrome (TS). Hand pattern profiles were calculated and compared with those of 110 normal individuals. Pearson correlation coefficient ( r) and multivariate discriminant analysis were used for pattern profile analysis. Pattern variability index, a measure of dysmorphogenesis, was calculated for LWD, TS, HCP, and normal controls. Results: Our results demonstrate that patients with LWD, TS, or HCP have distinct pattern profiles that are significantly different from each other and from those of normal controls. Discriminant analysis yielded correct classification of normal versus abnormal individuals in 84% of cases. Classification of the patients into LWD, TS, and HCP groups was successful in 75%. The correct classification rate was higher (85%) when differentiating two pathological groups at a time. Pattern variability index was not helpful for differential diagnosis of LWD, TS, and HCP. Conclusion: Patients with LWD, TS, or HCP have distinct MCPPs and can be successfully differentiated from each other using advanced MCPP analysis. Discriminant analysis is to be preferred over Pearson correlation coefficient because it is a more sensitive and specific technique. MCPP analysis is a helpful tool for differentiating between syndromes with similar clinical and radiological abnormalities.
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| 17. |
- Laurencikas, E, et al.
(författare)
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Swedish metacarpophalangeal standards compared with previously published norms
- 2000
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 41:5, s. 498-502
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Metacarpophalangeal lengths are used to create pattern profiles that are useful for assessment of skeletal dysplasias and malformation syndromes. The purpose of this study was to establish Swedish standards and compare them with previously published norms. Material and Methods: A group of healthy Swedish children was followed longitudinally from the age of 1 month to 18 years. The length of the tubular bones of the hand was measured on radiographs. In addition to the conventional measurements including epiphyses, diaphyseal lengths alone were recorded. Results: Means and standard deviations of the metacarpophalangeal lengths are presented by gender and age. Conclusion: In spite of reasonably good correlation to previously published norms, demonstrated deviations encourage us to recommend the use of local standards whenever available.
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