| 1. |
- Proos, Lemm A., et al.
(författare)
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Can the TW3 bone age determination method provide additional criteria for growth hormone treatment in adopted girls with early puberty? : A comparison of the Tanner-Whitehouse 3 method with the Greulich-Pyle and the Tanner-Whitehouse 2 methods
- 2010
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Ingår i: Hormone research in pædiatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 73:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Gonadotropin-releasing hormone analogues (GnRHa) are the accepted treatment of idiopathic central precocious puberty. As it has been found that growth velocity may be decreased with GnRHa treatment, clinical trials with GnRHa combined with growth hormone (GH) have been carried out. In a recent study 46 adopted girls with early or precocious puberty were randomly assigned to treatment with either GnRHa or GnRHa combined with GH, and followed to final height (FH). It was found that FH was significantly higher in the combined treatment group, 158.9 compared with 155.8 cm in the GnRHa treated group. In order to select the patients who could benefit from added GH, predictions of FH at the start of treatment according to the methods of bone age determination of Greulich-Pyle (GP) and Tanner-Whitehouse 2 (TW2) were compared. It was found that the GP method was the most useful method for patient selection. Recently, a revision of the Tanner-Whitehouse method, named Tanner-Whitehouse 3 (TW3), has been developed. The present study examined the usefulness of the TW3 method in selecting suitable patients for combined treatment. METHOD: The TW3 method bone age determinations of the 46 girls were compared to the GP and TW2 method determinations, using the differences between actual FH and predicted adult height (PAH). Beside accuracy of prediction of FH, the criteria of efficiency of selection and replicability were applied in the comparison. RESULTS: We found that the GP method, also when compared to the TW3 method, gave the most accurate prediction of the FH on only GnRHa treatment. This gives the best ground for selection of patients who can benefit from combined treatment. The GP method was also the most efficient in selecting patients, i.e., it could select the least number of patients that needed the combined treatment. The only drawback of the GP method was that it requires an experienced pediatric radiologist. Automated methods are being developed and may soon facilitate the use of the GP method for those less experienced. The FH after combined treatment could be predicted with an equation including PAH GP as well as PAH TW3 as variables. CONCLUSION: The GP method remains the most useful method for selection of those patients who will benefit most from the addition of GH to GnRHa in the treatment of idiopathic central precocious or early puberty. FH prediction after combined treatment requires PAH GP as well as PAH TW3.
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| 2. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Multiple epiphyseal dysplasia : A clinical and genetic study of 12 cases in a Swedish 6-generation family
- 2009
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 80:6, s. 711-715
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple epiphyseal dysplasia (MED) is a common genetically and clinically heterogeneous skeletal dysplasia characterized by early-onset osteoarthritis, mainly in the hip and knee, and mild-to-moderate short stature. Here we report on a 6-generation MED family with 17 affected members. METHOD: The clinical and radiographic data on the 12 affected members still living were scrutinized. A structured inquiry comprising state of health and MED-related symptoms since birth up to the present time and the osteoarthritis outcome (KOOS) questionnaire were sent to all living family members with MED. The 5 known gene loci for autosomal dominant MED were analyzed for linkage, using fluorescence-labeled microsatellite markers. Linkage was ascertained with markers close to the COL9A2 gene, which was analyzed for mutations by sequencing. RESULTS: We identified an exon 3 donor splice mutation in the COL9A2 gene in all affected family members. Clinical, radiographic, and questionnaire data from affected family members suggested that MED caused by COL9A2 mutations starts in early childhood with knee pain accompanied by delayed ossification of femoral epiphyses. The disease then either stabilizes during puberty or progresses with additional joints becoming affected; joint surgery might be necessary. The progression of the disease also affects muscles, with increasing atrophy, resulting in muscle fatigue and pain. Muscular atrophy has not been reported earlier in cases with COL9A2 mutations. INTERPRETATION: In a patient with clinically suspected or verified MED, it is important to perform DNA-based analysis to identify a possible disease-causing mutation. This information can be used to carry out genetic risk assessment of other family members and to achieve an early and correct diagnosis in the children.
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| 3. |
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| 4. |
- Stattin, Eva-Lena, et al.
(författare)
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Brachydactyly type A1 associated with unusual radiological findings and a novel Arg158Cys mutation in the Indian hedgehog (IHH) gene
- 2009
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Ingår i: European Journal of Medical Genetics. - : Elsevier. - 1769-7212 .- 1878-0849. ; 52:5, s. 297-302
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Tidskriftsartikel (refereegranskat)abstract
- Brachydactyly type A1 (BDA1; MIM 112500) is characterized by shortness or absence of the middle phalanx of the hands and feet. The condition is caused by heterozygous mutations in the Indian hedgehog (IHH) gene or a yet unidentified gene on chromosome 5p13. We investigated six affected members of a large Swedish family segregating autosomal dominant brachymesophalangia. Affected individuals show hypoplasia of the ulnar styloid processes, ulna minus, osteoarthritis, normal length of all distal phalanges and shortening or absence of the middle phalanges. Stationary ossicles or sesamoid bones were observed at the metacarpal heads in all patients. Genetic analysis of the family showed that the IHH-gene was linked to the disease (Z(max) 3.42 at theta 0.00) and sequence analysis of IHH revealed a novel c.472C > T transition in all affected family members. The mutation results in a p.158Arg > Cys substitution located in the highly conserved amino-terminal domain of IHH. This domain is of importance for the interaction between IHH and the Patched receptor. Our combined findings add radiological findings to the BDA1 phenotype and confirm a critical functional domain of IHH.
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| 5. |
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| 6. |
- Stattin, Eva-Lena, et al.
(författare)
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SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Vasterbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Tonsillar herniation, foramen magnum stenosis, and severe osteomyelitis of the jaw were common clinical features. Whole exome sequencing, verified by Sanger sequencing, identified a splice site mutation c.212 + 1 G > T in the SNX10 gene encoding sorting nexin 10. Sequence analysis of the SNX10 transcript in patients revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a premature stop (p.S66Nfs * 15). Haplotype analysis showed that all cases originated from a single mutational event, and the age of the mutation was estimated to be approximately 950 years. Functional analysis of osteoclast progenitors isolated from peripheral blood of patients revealed that stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) resulted in a robust formation of large, multinucleated osteoclasts which generated sealing zones; however these osteoclasts exhibited defective ruffled borders and were unable to resorb bone in vitro.
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| 7. |
- Wester, Ulrika, et al.
(författare)
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Chondrodysplasia punctata (CDP) with features of the tibia-metacarpal type and maternal phenytoin treatment during pregnancy
- 2002
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Ingår i: Prenatal Diagnosis. - : Wiley. - 0197-3851 .- 1097-0223. ; 22:8, s. 663-668
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Tidskriftsartikel (refereegranskat)abstract
- We describe a 2-year-old boy with chondrodysplasia punctata (CDP). The boy was exposed to phenytoin, in combination with carbamazepine, during pregnancy. There has been previous evidence for a connection between phenytoin exposure during pregnancy and chondrodysplasia punctata. The boy had clinical and some radiological characteristic features of CDP, of the tibia-metacarpal type. We know of no other report on a child exposed to phenytoin during pregnancy who developed CDP of this type.
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