Life expectancy for a person with Marfan syndrome has essentially doubled over the past four decades. During this period, the clinical histories of the organs managed routinely have improved, and ...will continue to be. Prominent examples are the eyes, the heart and aorta, and some features of the skeletal system. Meanwhile, the natural histories of organ systems that have not been subjected to treatment need to be described. This is particularly important as due to the improved life span many symptoms and organ systems are only recently being recognized as being intrinsic to Marfan syndrome. Examples are the distal aorta and peripheral arteries, ventricular function, the central nervous system, sleep apnea, and adiposity. As a result, each person with Marfan syndrome will need to be evaluated and followed by more specialists than previously. Moreover, the coordinator of diagnostic testing and clinical referral must be aware of the expanded phenotype as people with Marfan syndrome age and the importance of life-long management of classical and novel features. The benefits of increased longevity and its consequences need to be addressed by investigators, health-care providers, and patients alike.
Abstract Over the past 4 decades, remarkable progress in understanding the cause, pathogenesis, and management of the MFS has led to an increase in life expectancy to near normal for most patients. ...Accompanying this increased life span has been the emergence of previously rare or unanticipated clinical problems. Despite much more detailed knowledge of the molecular, cellular, and tissue effects of a mutation in FBN1, targeted, effective therapy remains elusive. Until such precision medicine takes hold, management will depend on early diagnosis, regular scrutiny by imaging, chronic β-blockade, and perhaps ARBs, and prophylactic cardiothoracic surgery. Without question, MFS will remain a fertile subject for basic, translational, and clinical research for the foreseeable future.
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a disorder of development of the vasculature characterized by telangiectases and arteriovenous malformations in specific ...locations. It is one of most common monogenic disorders, but affected individuals are frequently not diagnosed. The most common features of the disorder, nosebleeds, and telangiectases on the lips, hands, and oral mucosa are often quite subtle. Optimal management requires an understanding of the specific presentations of these vascular malformations, especially their locations and timing during life. Telangiectases in the nasal and gastrointestinal mucosa and brain arteriovenous malformations generally present with hemorrhage. However, complications of arteriovenous malformations in the lungs and liver are generally the consequence of blood shunting through these abnormal blood vessels, which lack a capillary bed and thus result in a direct artery-to-vein connection. Mutations in at least five genes are thought to result in hereditary hemorrhagic telangiectasia, but mutations in two genes (ENG and ACVRL1/ALK1) cause approximately 85% of cases. The frequency of arteriovenous malformations in particular organs and the occurrence of certain rare symptoms are dependent on the gene involved. Molecular genetic testing is used to establish the genetic subtype of hereditary hemorrhagic telangiectasia in a clinically affected individual and family, and for early diagnosis to allow for appropriate screening and preventive treatment.
As exacting as genetic and genomic testing have become, health professionals continue to encounter uncertainty in their applications to medical practice. As examining the human genome at more refined ...levels increases, so is the likelihood of encountering uncertainty about the meaning of the information. The history of this concept informs how we might confront and deal with uncertainty, and what the future might hold. Precision medicine holds great promise for establishing more accurate diagnoses, directing specific therapy to patients who will most benefit from it, and avoiding treatments in patients who are most likely to suffer adverse consequences, or at best not benefit. But its application depends importantly on the proper interpretation of a person’s genotype.
A major basis of precision medicine is determining a patient’s genetic susceptibility to disease, optimal therapies, and likelihood of adverse effects.How uncertainty in medicine has been recognized and interpreted generally has essential relevance to genomic uncertainty and precision medicine.As the technology to analyze a patient’s genes has dramatically accelerated, up to sequencing all 6.2 billion nucleotides in the genome, interpreting and applying the results has been accompanied by an increase in uncertainty.Comprehensive applications of precision medicine will depend on decreasing the uncertainty in interpreting a person’s genetic information.
Arachnodactyly represented in art Pyeritz, Reed E.
American journal of medical genetics. Part C, Seminars in medical genetics,
June 2021, 2021-06-00, 20210601, Volume:
187, Issue:
2
Journal Article
Arachnodactyly, a term used since 1902 to describe abnormally long (spider‐like) fingers, is a pathologic feature of several heritable conditions, notably the Marfan syndrome and congenital ...contractural arachnodactyly. A number of prominent artists, dating from the 16th to the 20th centuries, have depicted subjects with unusually long fingers, sometime associated with elongation of the body, neck and head. El Greco incorporated this style in many paintings. Little evidence supports any subject in any of these paintings as having a congenital deformity.
Abnormalities of the capillaries of the digits in hereditary hemorrhagic telangiectasia can be detected by shining through a narrow beam of light through the dorsal side and visualizing the ...vasculature on the palmar side, a procedure termed transillumination. This study was performed to determine if this method can detect digital vascular abnormalities in aortopathies and arteriopathies. Transillumination was performed in patients with Marfan syndrome (MFS), thoracic aortic aneurysm and dissection (TAAD), vascular Ehlers–Danlos syndrome (vEDS), bicuspid aortic valve with aortopathy, and arteriopathies without aortopathy. Subjects with no known vascular disorders were controls. Digital vascular abnormalities were present in some patients with all of the disorders and were especially frequent in MFS, TAAD, and vEDS. All patients had significantly more digital vascular abnormalities than control subjects. Transillumination can detect vascular abnormalities in digits of patients with a variety of conditions with aortopathy or arteriopathy.
Disease of the wall of the thoracic aorta has many causes: inflammation, infection and atherosclerosis are the most common 'acquired' causes, but even these have genetic predispositions. This article ...deals with aortic disease due to mutations in specific genes. The conditions can affect tissues and organs other than the aorta (syndromic) or be limited to the aorta (nonsyndromic).
A classification scheme based on the gene is emerging, those that affect primarily the extracellular matrix (e.g., FBN1, COL3A1), TGF-β signaling (e.g., TGFBR1, TGFB2), or vascular smooth muscle cell contractility (e.g., ACTA2, MYH11).
Understanding pathogenesis is driving the development of novel therapies, such as angiotensin receptor blockade, which is in clinical trial. However, recurrent imaging, restriction of exercise, β-adrenergic blockade, and prophylactic surgery remain effective in preventing dissection and sudden death.
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