Marfan syndrome: Evolving organ manifestations-A 10-year follow-up study.

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.

Dural ectasia in Marfan syndrome and other hereditary connective tissue disorders: a 10-year follow-up study.

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.

The pulmonary artery in patients with Marfan syndrome: a cross-sectional study.

PURPOSE: The objectives of this study were to establish the prevalence of pulmonary artery dilatation in Marfan syndrome using modern radiological methods and to correlate the diameter of the vessel with aortic disease. METHODS: Magnetic resonance or computed tomography imaging of the pulmonary artery and aorta was performed in 87 patients with proven Marfan syndrome. Diameters of the root and trunk of the pulmonary artery and of the aortic root were measured perpendicular to the long axes of the vessels. Pulmonary artery diameters were measured on axial images, and aortic diameters were assessed on oblique sagittal images. RESULTS: As compared with normal values in the literature, 47 of the 87 patients (54%) had widening of the trunk of the pulmonary artery (≥30 mm). Of these 47, 15% had no sign of disease of the ascending aorta. The mean (SD) ratio between the diameters of the root and trunk of the pulmonary artery was 1.18 (0.155). Multivariate analysis showed that surgery of the ascending aorta and high body surface area were associated with dilatation of the trunk of the pulmonary artery. CONCLUSIONS: Pulmonary artery dilatation is present in a high proportion of patients with Marfan syndrome as assessed using cutoff values based on measurements in the normal population. Severe disease of the ascending aorta correlates significantly with pulmonary artery trunk dilatation in patients with Marfan syndrome.

CT of the hips in the investigation of protrusio acetabuli in Marfan syndrome. A case control study.

OBJECTIVES: To establish the prevalence of protrusio acetabuli (PA) in adults fulfilling the Ghent criteria for Marfan syndrome (MFS), and in a normal adult population. METHODS: 105 adults with probable MFS and 107 controls were included. CT of the hips was obtained. A qualitative assessment of PA was performed. A new method for estimating the degree of PA was introduced with measurement of the parameter CWD (circle-wall distance). Results were compared to an alternative method based on MRI [1]. RESULTS: 87 of the study group fulfilled the Ghent criteria of MFS (Ghent positives), and 18 did not (Ghent negatives). PA was diagnosed qualitatively in 74.7% of Ghent positive persons, in 27.8% of Ghent negative persons, and in 3.7% of the controls. CWD was significantly different between the three groups (p < 0.001). A slight but significant gender difference was found in Ghent positive persons only. The alternative method did not differentiate between the groups with respect to PA, but showed a significant difference between genders. CONCLUSIONS: PA was found significantly more often in MFS persons than in controls. Our method was found to be robust and highly reproducible, giving a direct measurement of pelvic protrusion irrespective of pelvic shape.

Prevalence data on all Ghent features in a cross-sectional study of 87 adults with proven Marfan syndrome.

The prevalence of each single feature in the Ghent criteria in patients with Marfan syndrome (MFS) is not known. To elucidate this, a cross-sectional study of 105 adults with presumed MFS was carried out. All patients were examined by the same group of investigators with standardized and complete assessment of all features in the Ghent criteria. Eighty-seven (83%) fulfilled the criteria in 56 different variants. The most prevalent major criterion in Ghent-positive persons was dural ectasia (91%), followed by major genetic criterion (89%) and ectopic lenses (62 %). In 14 persons (16%), the diagnosis was dependent on the dural findings. In all, 79% fulfilled both major dural and major genetic (positive family history and/or FBN1 mutation) criteria, suggesting that most patients with MFS might be identified by investigating these criteria. A history or finding of ascending aortic disease was present in 46 patients (53%). This low prevalence might partly reflect a high number of diagnosed patients encompassing the whole spectrum of the syndrome. The study confirms the need to examine for the complete set of features in the Ghent criteria to identify all patients with MFS. The majority of persons with MFS might be identified by the combined assessment of dura mater and family history, supplemented with DNA analysis in family-negative cases. The low prevalence of ascending aortic disease might indicate better future prospects in an adult population than those traditionally considered.

Search for correlations between FBN1 genotype and complete Ghent phenotype in 44 unrelated Norwegian patients with Marfan syndrome.

In monogenic disorders, correlation between genotype and phenotype is a premise for predicting prognosis in affected patients. Predictive genetic testing may enable prophylaxis and promote clinical follow-up. Although Marfan syndrome (MFS) is known as a monogenic disorder, according to the present diagnostic criteria a mutation in the gene FBN1 is not sufficient for the diagnosis, which also depends on the presence of a number of clinical, radiological, and other findings. The fact that MFS patient cohorts only infrequently have been examined for all relevant phenotypic manifestations may have contributed to inconsistent reports of genotype-phenotype correlations. In the Norwegian Study of Marfan syndrome, all participants were examined for all findings contained in the Ghent nosology by the same investigators. Mutation identification was carried out by robot-assisted direct sequencing of the entire FBN1 coding sequence and MLPA analysis. A total of 46 mutations were identified in 44 unrelated patients, all fulfilling Ghent criteria. Although no statistically significant correlation could be obtained, the data indicate associations between missense or splice site mutations and ocular manifestations. While mutations in TGF-domains were associated with the fulfillment of few major criteria, severe affection was indicated in two cases with C-terminal mutations. Intrafamilial phenotypic variation among carriers of the same mutation, suggesting the influence of epigenetic facors, complicates genetic counseling. The usefulness of predictive genetic testing in FBN1 mutations requires further investigation.

[Pyridoxine-dependent seizures]. / Pyridoksinavhengige krampar.

BACKGROUND: Pyridoxine-dependent seizures is an autosomal, recessively inherited inborn error of metabolism with recurrent long-lasting seizures with onset usually in infancy, but also up to three years of age. The seizures are resistant to conventional anticonvulsants. The condition ends fatally if diagnosis and administration of pyridoxine (vitamin B6 ) in pharmacological doses is delayed too long. MATERIAL AND METHODS: A ten-year-old girl who we believe is affected with this condition is presented. A review of the condition based on relevant literature is given. RESULTS AND INTERPRETATION: The disorder is rare, but may be underdiagnosed. This case report highlights the serious convulsive condition, the problems in diagnosis and treatment, the delayed development before diagnosis and a very positive development during pyridoxine treatment. The condition is variable in clinical expression, and a variety of clinical seizure types may be seen. Diagnosis is clinical and based on response to pyridoxine administration. The pyridoxine dose needed varies, and the aim of treatment is seizure control as well as optimal intellectual development. Prognosis is variable; many are retarded, especially in their speech development. A gene on chromosome 5 is linked to the disorder, but the gene and its product are unknown.