Benedicte Paus

• Bøker, Tordis; Kirkhus, Eva; Pripp, Are Hugo; Rand-Hendriksen, Svend; Paus, Benedicte & Smith, Hans Jørgen [Show all 7 contributors for this article] (2025). The natural history of protrusio acetabuli in Marfan syndrome and other hereditary connective tissue disorders: a 10-year follow-up CT study. Orphanet Journal of Rare Diseases. 20(1). doi: 10.1186/s13023-025-03628-0. Full text in Research Archive Show summary

  Objectives To explore the natural history of protrusio acetabuli (PA) in adults with Marfan syndrome (MFS) via a prospective 10-year follow-up study. Methods 2014 through 2015, 62 of 87 survivors from a nationwide cross-sectional study of 105 adults with presumed MFS were re-examined. At follow-up, MFS was diagnosed in 46 participants, and other hereditary connective tissue disorders in 12 participants. As in the baseline study, matched hospital controls were collected for comparison. CT images were obtained of the hips. PA was evaluated quantitatively and qualitatively. Measurements were performed according to the circle-wall distance method. The data was analysed with paired t test, and McNemar’s test. A receiver operating characteristic (ROC) curve was constructed for the circle-wall distance. Results There was no increase in the number of hips diagnosed with PA or in the circle-wall distance. PA was diagnosed in 58 of 87 hips in patients with MFS and in 71 of 111 hips in all patients with hereditary connective tissue disorders. Significantly more patients with MFS than controls had PA. Conclusion The prevalence and degree of PA remained unchanged after 10 years. The circle-wall distance seems to have a good ability to discriminate between individuals with MFS and individuals without any known connective tissue disorder. Suggested cutoff level for the circle-wall distance: 2 mm.

• Holt, Margrethe Flesvig; Michelsen, Annika Elisabet; Flø, August Magnus Stensrød; Khan, Yusuf; Bjørnø, Vilde & Skjelland, Mona [Show all 17 contributors for this article] (2025). Hepatocyte Growth Factor: A Marker of Cardiac Function, Mortality, and Disease Subtype in Cardiac Amyloidosis. JACC: Advances. 4(6). doi: 10.1016/j.jacadv.2025.101828. Full text in Research Archive
• Seim, Bjørn Edvard; Holt, Margrethe Flesvig; Ratajska, Aleksandra; Michelsen, Annika Elisabet; Ringseth, Monica Myklebust & Halvorsen, Bente [Show all 14 contributors for this article] (2022). Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases. Frontiers in Cardiovascular Medicine. 9, p. 1–9. doi: 10.3389/fcvm.2022.1073069. Full text in Research Archive Show summary

  Background: In approximately 20% of patients with thoracic aortic aneurysms or dissections a heritable thoracic aortic disease (HTAD) is suspected. Several monogenic connective tissue diseases imply high risk of aortic disease, including both non-syndromic and syndromic forms. There are some studies assessing inflammation and extracellular matrix remodeling in patients with non-hereditary aortic disease, but such studies in patients with hereditary diseases are scarce.<p> <p>Aims: To quantify markers of extracellular matrix (ECM) and inflammation in patients with vascular connective tissue diseases versus healthy controls. <p>Methods: Patients with Loeys-Dietz syndrome (LDS, n = 12), Marfan syndrome (MFS, n = 11), and familial thoracic aortic aneurysm 6 (FTAA6, n = 9), i.e., actin alpha 2 (ACTA2) pathogenic variants, were recruited. Exome or genome sequencing was performed for genetic diagnosis. Several markers of inflammation and ECM remodeling were measured in plasma by enzyme immunoassays. Flow cytometry of T-cell subpopulations was performed on a subgroup of patients. For comparison, blood samples were drawn from 14 healthy controls. <p>Results: (i) All groups of HTAD patients had increased levels matrix metalloproteinase-9 (MMP-9) as compared with healthy controls, also in adjusted analyses, reflecting altered ECM remodeling. (ii) LDS patients had increased levels of pentraxin 3 (PTX3), reflecting systemic inflammation. (iii) LDS patients have increased levels of soluble CD25, a marker of T-cell activation. <p>Conclusion: Our data suggest that upregulated MMP-9, a matrix degrading enzyme, is a common feature of several subgroups of HTAD. In addition, LDS patients have increased levels of PTX3 reflecting systemic and in particular vascular inflammation.

• Ratajska, Aleksandra; Vigeland, Magnus Dehli; Wirgenes, Katrine Verena; Krohg-Sørensen, Kirsten & Paus, Benedicte (2022). The use of segregation analysis in interpretation of sequence variants in SMAD3: A case report. Molecular Genetics & Genomic Medicine. ISSN 2324-9269. doi: 10.1002/mgg3.2107. Full text in Research Archive Show summary

  Background While representing a significant improvement, the introduction of next-generation sequencing in genetic diagnosis also prompted new challenges. Despite widely recognized consensus guidelines for the interpretation of sequence variants, many variants remain unclassified or are discordantly interpreted. In heritable thoracic aortic aneurysms with dissection (HTAAD), most cases are caused by a heterozygous, private missense mutation, possibly contributing to the relatively common reports of variants with uncertain significance in this group. Segregation analysis necessitates advanced likelihood-based methods typically inaccessible to non-experts and is hampered by reduced penetrance, possible phenocopies, and non-availability of DNA from deceased relatives. Methods In this report, challenges in variant interpretation and the use of segregation analyses were illustrated in two families with a suspected HTAAD disorder. The R package segregatr, a novel implementation of full-likelihood Bayes factor (FLB), was performed to explore the cosegregation of the variants in these families. Conclusion Using the R package segregatr, cosegregation in the reported families concluded with strong and supporting evidence for pathogenicity. Surveillance of families in a multidisciplinary team enabling systematic phenotype description for standardized segregation analysis with a robust calculation method may be imperative for reliable variant interpretation in HTAAD.

• Gjersvik, Petter & Paus, Benedicte (2021). Mutasjoner som endrer proteinets funksjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(12), p. 1–4. doi: 10.4045/tidsskr.21.0377. Full text in Research Archive
• Henriksen, Mari Wold; Breck, Hilde; Tetzchner, Stephen von; Paus, Benedicte & Skjeldal, Ola, Hunsbeth (2020). Medical Issues in Adults with Rett Syndrome - A National Survey. Developmental Neurorehabilitation. ISSN 1751-8423. 23(2), p. 106–112. doi: 10.1080/17518423.2019.1646341. Full text in Research Archive Show summary

  Objectives: To examine main health issues in a population of females with Rett syndrome, with a focus on individuals aged 36 or older. Methods: A national survey including 85 females, divided into a younger (1-20 years), a middle (21-35 years) and an older group (36-66 years). Data include clinical examination, medical records and parental interviews. Prevalences of six main medical issues (scoliosis, ambulation, growth, respiration, gastrointestinal dysmobility and epilepsy) and severity scores in the three groups were compared. Results: Mean severity scores were 11.8, 15.1 and 13.7 (from younger to older), and the difference between the younger and the middle group was significant. No other major significant prevalence differences were observed. Conclusions: Most main medical issues in Rett syndrome continued to be a major concern in adulthood, but health did not seem to decline with increasing age. The results emphasize the need for clinical follow-up throughout adulthood. Keywords: Rett syndrome; adulthood; ageing; clinical management; morbidity.

• Henriksen, Mari Wold; Breck, Hilde; Sejersted, Yngve; Diseth, Trond H; Tetzchner, Stephen von & Paus, Benedicte [Show all 7 contributors for this article] (2020). Genetic and clinical variations in a Norwegian sample diagnosed with Rett syndrome. Brain & development (Tokyo. 1979). ISSN 0387-7604. 42(7), p. 484–495. doi: 10.1016/j.braindev.2020.03.008. Full text in Research Archive Show summary

  Background and purpose: Rett syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutations in MECP2. The diagnostic criteria of RTT are clinical; mutations in MECP2 are neither diagnostic nor necessary, and a mutation in another gene does not exclude RTT. We attempted to correlate genotype and phenotype to see if there are significant clinical associations. Methods: All available females diagnosed with RTT in Norway were invited to the study. Parents were interviewed, the girl or woman with RTT examined and medical records reviewed. All diagnoses were revisited according to the current diagnostic criteria and exome-based sequencing analyses were performed in individuals without an identified causative mutation. Participants were categorized according to genotypes and RTT diagnosis. Individuals with RTT with and without mutations in MECP2 were compared. Results: Ninety-one individuals were included. A presumed causative mutation was identified in 86 individuals, of these, mutations in MECP2 in 77 individuals and mutations in SMC1A, SYNGAP1, SCN1A, CDKL5, FOXG1 or chromosome 13q in nine. Seventy-two individuals fulfilled the diagnostic criteria for classic and 12 for atypical RTT. Significant differences in early development, loss of hand use and language, intense eye gaze and the presence of early onset epilepsy were revealed in individuals with RTT according to their MECP2 genotypic status. Conclusion: Using the current diagnostic criteria, genetic and clinical variation in RTT is considerable. Significant differences between individuals with RTT with and without MECP2 mutations indicate that MECP2 is a major determinant for the clinical phenotype in individuals with RTT. Keywords: Clinical phenotype; Epilepsy; Exome sequencing; Genetic variation; MECP2; Rett syndrome.

• Böker, Tordis; Vanem, Thy Thy; Pripp, Are Hugo; Rand-Hendriksen, Svend; Paus, Benedicte & Smith, Hans-Jørgen [Show all 7 contributors for this article] (2019). Dural ectasia in Marfan syndrome and other hereditary connective tissue disorders: a 10-year follow-up study. The spine journal. ISSN 1529-9430. 19(8), p. 1412–1421. doi: 10.1016/j.spinee.2019.04.010. Full text in Research Archive Show summary

  BACKGROUND CONTEXT Dural ectasia is widening of the dural sac often seen in patients with Marfan syndrome and other hereditary connective tissue disorders. Dural ectasia can cause specific symptoms and is associated with surgical complications. The knowledge on how and at which age dural ectasia develops is incomplete. There is no established gold standard for diagnosing dural ectasia, making it difficult to compare results from different studies. PURPOSE Our primary aim was to explore whether the radiological findings of dural ectasia changed after 10 years in an adult cohort with suspected Marfan syndrome. Our secondary aim was to re-evaluate the radiological criteria of dural ectasia. STUDY DESIGN Prospective cohort study. PATIENT SAMPLE Sixty-two persons from a cross-sectional study of 105 persons with suspected Marfan syndrome were included in a 10-year follow-up of dural ectasia. Forty-six were diagnosed with Marfan syndrome, 7 with Loeys-Dietz syndrome, and 5 with other hereditary connective tissue disorders. For comparison 64 matched hospital controls were evaluated. OUTCOME MEASURES Previously used radiological criteria for dural ectasia based on quantitative measurements of the lumbosacral spine. METHODS MRI of the lumbosacral spine was performed if not contraindicated, and if so then CT was performed. Differences in the study group between baseline and follow-up were assessed with paired Student t test, Wilcoxon rank signed test, and McNemar test. Receiver operating characteristic curves were constructed to assess the ability of radiological measurement to differentiate between the study and control group. RESULTS Fifty-two of 58 patients with hereditary connective tissue disorders and 11 controls had dural ectasia at follow-up. Forty-five Marfan patients had dural ectasia at follow-up vs. 41 at baseline. Five Loeys-Dietz patients had dural ectasia at follow-up vs. four at baseline. Twenty-four Marfan and 2 Loeys-Dietz patients had anterior sacral meningocele at follow-up, compared with 21 and 1, respectively, at baseline. Three Marfan patients developed herniation of a nerve root sleeve during follow-up. This was not seen in other individuals. The dural sac ended significantly lower at follow-up, and the dural sac ratio at level L5 was significantly increased from baseline in the Marfan patients. CONCLUSIONS In Marfan and Loeys-Dietz syndrome, dural ectasia may present or worsen during adulthood. The cut-off value of dural sac ratio at level S1 is suggested elevated to 0.64. The results from the present study may help as guidance for appropriate follow-up of patients with dural ectasia.

• Vanem, Thy Thy; Böker, Tordis; Sandvik, Gunhild Falleth; Kirkhus, Eva Astrid; Smith, Hans-Jørgen & Andersen, Kai [Show all 13 contributors for this article] (2019). Marfan syndrome: Evolving organ manifestations-A 10-year follow-up study. American Journal of Medical Genetics. Part A. ISSN 1552-4825. 182(2), p. 397–408. doi: 10.1002/ajmg.a.61441. Full text in Research Archive Show summary

  The age‐dependent penetrance of organ manifestations in Marfan syndrome (MFS) is not known. The aims of this follow‐up study were to explore how clinical features change over a 10‐year period in the same Norwegian MFS cohort. In 2003–2004, we investigated 105 adults for all manifestations in the 1996 Ghent nosology. Ten years later, we performed follow‐up investigations of the survivors (n = 48) who consented. Forty‐six fulfilled the revised Ghent criteria. Median age: females 51 years, range 32–80 years; males 45 years, range 30–67 years. New aortic root dilatation was detected in patients up to 70 years. Ascending aortic pathology was diagnosed in 93 versus 72% at baseline. Sixty‐five percent had undergone aortic surgery compared to 39% at baseline. Pulmonary trunk mean diameter had increased significantly compared to baseline. From inclusion to follow‐up, two patients (three eyes) developed ectopia lentis, four developed dural ectasia, four developed scoliosis, three developed incisional or recurrent herniae, and 14 developed hindfoot deformity. No changes were found regarding protrusio acetabuli, spontaneous pneumothorax, or striae atrophicae. The study confirms that knowledge of incidence and progression of organ manifestations throughout life is important for diagnosis, treatment, and follow‐up of patients with verified or suspected MFS.

• Pope, Marita Knudsen; Ratajska, Aleksandra; Johnsen, Hilde; Rypdal, Karoline Bjarnesdatter; Sejersted, Yngve & Paus, Benedicte (2019). Diagnostics of Hereditary Connective Tissue Disorders by Genetic Next-Generation Sequencing. Genetic Testing and Molecular Biomarkers. ISSN 1945-0265. 23(11), p. 783–790. doi: 10.1089/gtmb.2019.0064. Full text in Research Archive Show summary

  Aims: This quality analysis study was designed to review the indications, reports, and clinical consequences of 438 diagnostic next-generation sequencing (NGS) gene panel analyses for hereditary connective tissue disorders (HCTD). Methods: Molecular analyses were retrieved from laboratory databases and patient records, and compared to the clinical information in the requisition and classified according to the Human Phenotype Ontology. Results: In 123 of 438 NGS analyses, 156 sequence variants were reported in 33 of 54 genes analyzed. NGS analyses and, in some cases, postanalytic assessment resulted in identification of pathogenic variants in 40 (9%) of patients, and variants of uncertain significance were identified in 83 (19%) of cases analyzed. While cardiovascular abnormalities were the most common phenotype noted in the requisitions, no specific organ system could be identified in which the reported symptoms provided an actionable indication for the analysis. Certain health issues recorded in the patients’ records were found to be frequently left out of requisitions. Conclusions: The interpretation of genetic sequence variants continues to be a significant challenge in HCTD. Although not associated with the highest diagnostic yield, cardiovascular disease and family history may be suitable indications for NGS due to the clinical consequences of the identification of a known or likely causative sequence variant for a vascular HCTD in patients and relatives.

• Paus, Benedicte (2018). Kanskje teste, ofte utrede, alltid veilede. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(13), p. 1–3. doi: 10.4045/tidsskr.18.0574. Full text in Research Archive
• Henriksen, Mari Wold; Breck, Hilde; Tetzchner, Stephen von; Paus, Benedicte; Skjeldal, Ola & Brodtkorb, Eylert (2018). Epilepsy in classic Rett syndrome: Course and characteristics in adult age. Epilepsy Research. ISSN 0920-1211. 145, p. 134–139. doi: 10.1016/j.eplepsyres.2018.06.012. Full text in Research Archive Show summary

  Purpose Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females. Epilepsy is a major clinical feature, but its long-term course in RTT has not been sufficiently explored. This study addresses the development of the epilepsy in adults with RTT. Methods Available females diagnosed with RTT in Norway were asked to participate. Parents/caregivers were interviewed, the girls/women were examined and their medical records reviewed. Participants were categorized according to age, epilepsy, seizure patterns and mutation severity groups. RTT severity was assessed (epilepsy score excluded). Results 70 females with classic RTT were included. A presumed pathogenic mutation in MECP2 was found in 96%. The presence of active epilepsy (seizures last five years) was similar in all age groups above the age of ten: 11 (65%) in adolescents (11–20 years), 9 (60%) in young adults (21–30 years) and 14 (67%) in participants above 30 years of age. Tonic-clonic seizures within the last year were present in 55, 67 and 64%, and ≥ weekly seizures occurred in 27, 45 and 50% in the respective age groups. Among participants with active epilepsy, 69% had unremitting seizures, whereas 31% had experienced remissions for more than six months during the last five years. In the oldest group (>30 years), only 19% had obtained seizure control for >5 years, and 14% had never experienced seizures. Seizure activity correlated with RTT severity score, whereas the relationship to mutation type remained ambiguous. Conclusion Epilepsy continues to be a major concern in adults with RTT. Two thirds of women above 30 years of age remained with active epilepsy and 50% of them had seizures at least weekly.

• Henriksen, Mari Wold; Ravn, Kirstine; Paus, Benedicte; Tetzchner, Stephen von & Skjeldal, Ola (2018). De novo mutations in SCN1A are associated with classic Rett syndrome: A case report. BMC Medical Genetics. 19(184), p. 1–5. doi: 10.1186/s12881-018-0700-z. Full text in Research Archive Show summary

  Background Rett syndrome (RTT) is a neurodevelopmental disorder. In more than 95% of females with classic RTT a pathogenic mutation in MECP2 has been identified. This leaves a small fraction of classic cases with other genetic causes. So far, there has not been reported any other gene that may account for the majority of these cases. Case presentation We describe two females who fulfill the diagnostic criteria for classic RTT, with pathogenic de novo mutations in SCN1A, which usually leads to Dravet syndrome. The developmental history and clinical features of these two females fits well with RTT, but they do have an unusual epileptic profile with early onset of seizures. Investigation of mRNA from one of the females showed a significantly reduced level of MECP2 mRNA. Conclusions To our knowledge, this is the first report suggesting that SCN1A mutations could account for a proportion of the females with classic RTT without MECP2 mutations. As a consequence of these findings SCN1A should be considered in the molecular routine screening in MECP2-negative individuals with RTT and early onset epilepsy.

• Riise, Nina; Lindberg, Bjørn; Kulseth, Mari Ann; Fredwall, Svein Otto; Lundby, Rigmor & Estensen, Mette-Lise [Show all 10 contributors for this article] (2018). Clinical diagnosis of Larsen syndrome, Stickler syndrome and Loeys-Dietz syndrome in a 19-year old male: a case report. BMC Medical Genetics. 19(155), p. 1–7. doi: 10.1186/s12881-018-0671-0. Full text in Research Archive Show summary

  Background Larsen syndrome is a hereditary disorder characterized by osteochondrodysplasia, congenital large-joint dislocations, and craniofacial abnormalities. The autosomal dominant type is caused by mutations in the gene that encodes the connective tissue protein, filamin B (FLNB). Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by arterial aneurysms, dissections and tortuosity, and skeletal, including craniofacial, manifestations. Mutations in five genes involved in the transforming growth factor beta (TGF-β) signaling pathway cause five types of LDS. Stickler syndrome is a genetically heterogeneous arthro-ophthalmopathy caused by defects in collagen, exhibiting a wide specter of manifestations in connective tissue. A rare case is reported that was diagnosed with all these three hereditary connective tissue disorders. Case presentation A 19 year-old, Norwegian male with a clinical diagnosis of Larsen syndrome and with healthy, non-consanguineous parents attended a reference center for rare connective tissue disorders. Findings at birth were hypotonia, joint hypermobility, hyperextended knees, adductovarus of the feet, cervical kyphosis, craniofacial abnormalities, and an umbilical hernia. From toddlerhood, he required a hearing aid due to combined conductive and sensorineural hearing loss. Eye examination revealed hyperopia, astigmatism, and exotropia. At 10 years of age, he underwent emergency surgery for rupture of an ascending aortic aneurysm. At 19 years of age, a diagnostic re-evaluation was prompted by the findings of more distal aortic dilation, tortuosity of precerebral arteries, and skeletal findings. High throughput sequencing of 34 genes for hereditary connective tissue disorders did not identify any mutation in FLNB, but did identify a de novo missense mutation in TGFBR2 and a nonsense mutation in COL2A1 that was also present in his unaffected father. The diagnosis was revised to LDS Type 2. The patient also fulfills the proposed criteria for Stickler syndrome with bifid uvula, hearing loss, and a known mutation in COL2A1. Conclusion LDS should be considered in patients with a clinical diagnosis of Larsen syndrome, in particular in the presence of arterial aneurysms or tortuosity. Due to genetic heterogeneity and extensive overlap of clinical manifestations, genetic high throughput sequencing analysis is particularly useful for the differential diagnosis of hereditary connective tissue disorders.

• Vanem, Thy Thy; Geiran, Odd; Krohg-Sørensen, Kirsten; Røe, Cecilie; Paus, Benedicte & Rand-Hendriksen, Svend (2018). Survival, causes of death, and cardiovascular events in patients with Marfan syndrome. Molecular Genetics & Genomic Medicine. ISSN 2324-9269. 6(6), p. 1114–1123. doi: 10.1002/mgg3.489. Full text in Research Archive Show summary

  Background To explore survival, causes of death, and the prevalence of cardiovascular events in a Norwegian Marfan syndrome (MFS) cohort. MFS is a heritable connective tissue disorder associated with reduced life expectancy–primarily due to aortic pathology. Methods A follow‐up study of 84 MFS adults, initially investigated in 2003–2004. In 2014–2015, 16 were deceased, 47 of 68 survivors consented to new clinical investigations. Analyses of events were performed for 47 survivors and 16 deceased at follow‐up. Standardized mortality ratios (SMR), using the mortality rate of the Norwegian population as reference, were calculated for all 84 and calculated for men and women separately. Causes of death and information on cardiovascular events were retrieved from death certificates and medical records. Results Standardized mortality ratios (95% confidence interval): for the whole cohort: 5.24 (3.00–8.51); for men: 8.20 (3.54–16.16); for women: 3.85 (1.66–7.58). Cardiovascular causes were found in 11 of 16 deceased, eight of these related to aortic pathology. Cancer was the cause of death in three patients. At follow‐up, 51% had new cardiovascular events; 59% had undergone aortic surgery. Men experienced aortic events at younger age than women. 32% of the survivors were not followed‐up as recommended. Conclusion Life expectancy is reduced in this MFS cohort compared to the Norwegian population. Cardiovascular complications develop throughout life, particularly aortic pathology, the major cause of death in MFS. Death and aortic pathology seem to occur earlier in men. There is a need to improve follow‐up according to guidelines.

• Krohg-Sørensen, Kirsten; Lingaas, Per Snorre; Lundblad, Runar; Seem, Egil; Paus, Benedicte & Geiran, Odd (2017). Cardiovascular surgery in Loeys-Dietz syndrome types 1-4. Journal of Cardiothoracic Surgery. 52(6), p. 1125–1131. doi: 10.1093/ejcts/ezx147. Full text in Research Archive
• Nordstrøm, Marianne; Paus, Benedicte; Retterstøl, Kjetil & Kolset, Svein Olav (2016). The prevalence of metabolic risk factors of atherosclerotic cardiovascular disease in Williams syndrome, Prader–Willi syndrome, and Down syndrome. Journal of Intellectual & Developmental Disability. ISSN 1366-8250. 41(3), p. 187–196. doi: 10.3109/13668250.2016.1167845. Full text in Research Archive
• Nordstrøm, Marianne; Paus, Benedicte; Andersen, Lene Frost & Kolset, Svein Olav (2015). Dietary aspects related to health and obesity in Williams syndrome, Down syndrome, and Prader - Willi syndrome :. Food & Nutrition Research (FNR). ISSN 1654-6628. 59(25847). doi: 10.3402/fnr.v59.25487. Full text in Research Archive
• Drolsum, Liv; Rand-Hendriksen, Svend; Paus, Benedicte; Geiran, Odd & Semb, Svein Ove (2015). Ocular findings in 87 adults with Ghent-1 verified Marfan syndrome. Acta Ophthalmologica. ISSN 1755-375X. 93(1), p. 46–53. doi: 10.1111/aos.12448. Full text in Research Archive Show summary

  Purpose To study ocular characteristics in 87 patients with verified Marfan syndrome (MFS) based on the Ghent criteria from 1996 (Ghent-1). Methods The position of the lens was noted by observing the eye in different gaze directions in maximal mydriasis during slit lamp examination. Ectopia lentis (EL) was classified as subluxated (dislocation slightly backwards) or luxated (vertical or horizontal displacement). Corneal curvature, axial length (AL), corneal diameter, central corneal thickness, anterior chamber depth, lens thickness, condition of the iris, intraocular pressure, spherical equivalent and visual acuity were also investigated. Results EL was found in 108 eyes (62.1%). Of the 68 phakic eyes with EL, 43 (63.2%) had subluxation. Mean AL was 24.80 ± 2.57 mm, and the AL was above 23.5 mm in 65.3%. Mean keratometry (K) in phakic eyes was 41.79 ± 1.70 diopters (D), and the K value was <41.5D in 46.8%. Iris hypoplasia was found in 3.4%. Myopia above 3D occurred in 38.4% of the phakic eyes. Mean binocular logMAR was 0.10 ± 0.32. Only five patients (5.7%) had a logMAR more than 0.5. These 5 patients had EL, and 4 of them were amblyopic. Conclusion In this strictly defined MFS group fulfilling the Ghent-1 criteria, the prevalence of EL was 62.1%. In many cases, the dislocation of the lens was subtle. On average, the corneas were flattened and the globe length was increased. Only a few patients were visually impaired. Children with MFS should have a thorough follow up to avoid amblyopia.

• Abrahamsen, Bjørg Johanne; Kulseth, Mari Ann & Paus, Benedicte (2015). A 19-year-old man with relapsing bilateral pneumothorax, hemoptysis, and intrapulmonary cavitary lesions diagnosed with vascular ehlers-danlos syndrome and a novel missense mutation in COL3A1. Chest. ISSN 0012-3692. 147(5), p. e166–e170. doi: 10.1378/chest.13-3002. Full text in Research Archive
• Tjeldhorn, Lena; Amundsen, Svanstrøm Silja; Barøy, Tuva; Rand-Hendriksen, Svend; Geiran, Odd & Frengen, Eirik [Show all 7 contributors for this article] (2015). Qualitative and quantitative analysis of FBN1 mRNA from 16 patients with Marfan Syndrome. BMC Medical Genetics. 16(113). doi: 10.1186/s12881-015-0260-4. Full text in Research Archive Show summary

  Background Pathogenic mutations in FBN1, encoding the glycoprotein, fibrillin-1, cause Marfan syndrome (MFS) and related connective tissue disorders. In the present study, qualitative and quantitative effects of 16 mutations, identified in FBN1 in MFS patients with systematically described phenotypes, were investigated in vitro. Methods Qualitative analysis was performed with reverse transcription-PCR (RT-PCR) and gel electrophoresis, and quantitative analysis to determine the FBN1 mRNA levels in fibroblasts from the 16 patients with MFS was performed with real-time PCR. Results Qualitative analysis documented that the mutations c.4817-2delA and c.A4925G led to aberrant FBN1 mRNA splicing leading to in frame deletion of exon 39 and in exon 39, respectively. No difference in the mean FBN1 mRNA level was observed between the entire group of cases and controls, nor between the group of patients with missense mutations and controls. The mean expression levels associated with premature termination codon (PTC) and splice site mutations were significantly lower than the levels in patients with missense mutations. A high level of FBN1 mRNA in the patient with the missense mutation c.G2447T did not segregate with the mutation in three of his first degree relatives. No association was indicated between the FBN1 transcript level and specific phenotypic manifestations. Conclusions Abnormal FBN1 transcripts were indicated in fibroblasts from patients with the splice site mutation c.4817-2delA and the missense mutation c.A4925G. While the mean FBN1 mRNA expression level in fibroblasts from patients with splice site and PTC mutations were lower than the mean level in patients with missense mutations and controls, inter-individual variability was high. The observation that high level of FBN1 mRNA in the patient with the missense mutation c.G2447T did not segregate with the mutation in the family suggests that variable expression of the normal FBN1 allele may contribute to explain the variability in FBN1 mRNA level.

• Nordstrøm, Marianne; Hansen, Bjørge Hermann; Paus, Benedicte & Kolset, Svein Olav (2013). Accelerometer-determined physical activity and walking capacity in persons with Down syndrome, Williams syndrome and Prader-Willi syndrome. Research in Developmental Disabilities. ISSN 0891-4222. 34(12), p. 4395–4403. doi: 10.1016/j.ridd.2013.09.021. Full text in Research Archive Show summary

  In this study we describe by use of accelerometers the total physical activity (PA), intensity pattern and walking capacity in 87 persons age 16–45 years with Down syndrome (DS), Williams syndrome (WS) and Prader–Willi syndrome (PWS). Participants were recruited from all over Norway, and lived either with their parents or in community residences with support. On average the participants generated 294 counts per minute (cpm) or 6712 steps per day, with most of the day spent in sedentary activity, 522 min/day, followed by 212 min/day in light PA, 71 min/day in lifestyle activity and 27 min/day in moderate-to-vigorous physical activity (MVPA). Inactivity was prevalent, as only 12% meet the current Nordic recommendations for PA. When compared, no differences for total physical activity or time in MVPA were observed between the three groups. However, participant with DS spent a mean of 73 min/day less and 43 min/day less in sedentary activities compared to participants with PWS and WS, respectively, (p = 0.011, 95% CI: −10.9; −80.1). In addition the DS-group spent a mean of 66 min/day more in light PA than the PWS-group and 41 min/day more than the WS-group, (p < 0.001, 95% CI: 29.3; 79.7). Participants with PWS spent on average 30 min/day less in lifestyle activities compared to both participants with DS and WS, (p < 0.001, 95% CI: −14.2; −45.4). No association between total PA and BMI were observed. Males were more active than females across all diagnoses. Males accumulated on average 85 counts per minutes more than females, (p = 0.002, 95% CI: 33.3; 136.7), 2137 more steps per day, (p = 0.002, 95% CI: 778; 3496). The mean walking capacity during six-minutes was 507 m (SD 112 m) for males and 466 m (SD 88 m) for females. Distance walked during testing decreased with 33.6 m when comparing normal or underweight participants to overweight participants, and 78.1 m when comparing overweight to obese participants (p < 0.001 95% CI: −40.4; −85.8). When adjusted for BMI no differences in walking capacity between the three genetic conditions were observed.

View all works in NVA

• Sekkelsten, Anna Irene Skei; Skattør, Thor Håkon; Holmstrøm, Henrik; Krohg-Sørensen, Kirsten & Paus, Benedicte (2025). Vascular findings in five unrelated children with vascular Ehlers-Danlos syndrome: A multi-case report. doi: 10.1016/j.ejmg.2025.105035. Full text in Research Archive Show summary

  Abstract Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder caused by heterozygous variants in COL3A1, leading to tissue and vessel fragility alongside an increased risk of potentially fatal aneurysms and dissections. Although vascular events most commonly manifest in adulthood, childhood events also occur. Knowledge on clinical manifestations in childhood and potential benefits of vascular surveillance is limited, and no evidence-based guidelines for predictive genetic testing and follow-up exist. We present five patients diagnosed with vEDS in childhood, focusing on vascular events. The patients receive follow-up at a multidisciplinary heritable thoracic aortic disease clinic at Oslo University Hospital and are registered in the associated patient registry. Two of the five patients experienced a childhood vascular event, both involving cerebral vessels. In one of these patients, the event may not be vEDS related. A mild aortic root dilatation was detected in one patient. No severe aortic events like dissection or rupture were reported in childhood, but one patient died from an aortic dissection in early adulthood despite normal findings on MRA scans in the years he received regular surveillance. Our findings highlight the variable expressivity of vEDS, including severe childhood vascular events. Further studies to evaluate the effect of surveillance are needed to form an evidence base for surveillance guidelines in pediatric patients. Established benefits of surveillance and management are essential for deciding on whether and when to perform predictive genetic testing of a child at risk.

• Iversen, Nina; Henriksson, Carola Elisabeth; Sletten, Marit; Le, Marie Skogstad; Lindberg, Beate & Andersen, Rune [Show all 7 contributors for this article] (2024). Heterozygosity for the Budapest 3 mutation in SERPINC1 in a family with thrombophilia and structural anomalies of the inferior vena cava. Thrombosis Journal. 22:75(1), p. 1–5. doi: 10.1186/s12959-024-00644-1. Full text in Research Archive Show summary

  Background Atresia of the infrarenal inferior vena cava (IVC) is associated with thrombophilia and antithrombin (AT) deficiency (ATD) due to homozygosity for the so-called Budapest 3 variant, c.391C > T, in the gene, SERPINC1. Case presentation We report on a father and his two sons that had severe thrombosis at a young age. One son had absence of, and the other had very gracile infrarenal IVC. The father had gracile vena iliaca. All had significant collateral building. AT activity was determined with four different methods and varied between moderately reduced and borderline normal values, depending on the method. While all were heterozygous for c.391C > T, the father was also heterozygous for a variant of uncertain significance in SERPINC1. Conclusions The findings support the association between c.391C > T in SERPINC1, thrombophilia, and atresia of the IVC system and indicate that even heterozygosity for c.391C > T may contribute to such anomalies. ATD detection was hampered by the varying sensitivity of methods used for AT activity measurement.

• Bratlie, Sigrid; Halvorsen, Kristin; Myskja, Bjørn Kåre; Mellegård, Hilde; Bjorvatn, Cathrine & Frost, Petter [Show all 19 contributors for this article] (2019). A novel governance framework for GMO : a tiered, more flexible regulation for GMOs would help to stimulate innovation and public debate. EMBO Reports. ISSN 1469-221X. 20(5), p. 1–4. doi: 10.15252/embr.201947812. Full text in Research Archive
• Paus, Benedicte (2018). B. Paus svarer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(16), p. 1502–1503. doi: 10.4045/tidsskr.18.0735. Full text in Research Archive
• Paus, Benedicte (2018). Kanskje teste, ofte utrede, alltid veilede. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(13), p. 1211–1211. Full text in Research Archive

View all works in NVA