Down syndrome with co-occurring Marfan syndrome

Down syndrome (DS) and Marfan syndrome (MFS) are two unique genetic disorders that share limited phenotypic overlap. There are very few reported cases in the existing literature on overlapping DS and MFS. Although these two disorders are phenotypically unique, features present in these cases are variable, resulting in mixed and dominant expressions of particular features. We present the first adolescent case of trisomy 21 associated DS and fibrillin-1 gene associated MFS in the literature who had a height at 90th percentile for an 11-year old boy and discuss the implications of this case in terms of future medical care when these two genetic syndromes are present in the same individual. Understanding of certain features of the ‘non-dominating’ syndrome is crucial for clinicians to recognise when DS co-occurs with MFS. Close monitoring of the cardiovascular, ophthalmologic and musculoskeletal systems is recommended if both syndromes are diagnosed given that both can be independently associated with disorders in these organ systems.

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REHABILITASI MEDIK PADA SINDROM MARFAN

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.6.3.2014.6322 ◽

2014 ◽

Vol 6 (3) ◽

Author(s):

Drahma Kusmarwaty ◽

Theresia I. Mogi

Keyword(s):

Marfan Syndrome ◽

Clinical Manifestations ◽

Joint Hypermobility ◽

Functional Training ◽

Physical Strength ◽

Organ Systems ◽

The Family ◽

Fibrillin 1 ◽

Musculoskeletal Systems ◽

Dominant Condition

Abstract: Marfan Syndrome (MS) is an autosomal dominant condition of the connective tissue that involves the ocular, cardiovascular and musculoskeletal systems. MS is caused by mutations in the fibrillin-1 gene, leading to joint ligaments flaccidity, joint hypermobility and overgrowth of the long bones. The diagnosis of MS is confirmed by using the Ghent nosology,through a comprehensive assessment largely based on a combination of major and minor clinical manifestations in various organ systems and the family history. The management of MS done with collaboration of team genetic clinic, cardiovascular, orthopedic, eye, and rehabilitation. The aims of rehabilitation of MS patients are to increase pulmonary function, improve exercise endurance, increases bone density, physical strength, prevent scoliosis, education about functional training on activity daily living.Keywords: Marfan syndrome, management, team rehabilitationAbstrak: Sindrom Marfan (SM) adalah autosom dominan dari jaringan ikat yang melibatkan ocular, kardiovaskular dan sistem musculoskeletal. Penyebab SM adalah mutasi dari gen fibrillin-1, yang menyebabkan flaccid ligamen sendi, hipermobilitas sendi dan overgrowth dari tulang panjang. Diagnosis dari SM dengan Ghent nosology, melalui penilaian secara menyeluruh berdasarkan kombinasi dari manifestasi klinik mayor dan minor pada sistem organ dan riwayat keluarga. Penanganan SM dilakukan dengan kolaborasi tim antara lain klinik genetik, kardiovaskular, orthopedi, mata, dan tim rehabilitasi. Tujuan dari rehabilitasi pada SM adalah meningkatkan fungsi paru, meningkatkan ketahanan latihan, meningkatkan densitas tulang, ketahanan fisik, mencegah skoliosis, edukasi mengenai functional training pada aktivitas kehidupan sehari-hari.Kata kunci: sindrom Marfan, penanganan, tim rehabilitasi

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A systematic study and literature review of parental somatic mosaicism of FBN1 pathogenic variants in Marfan syndrome

Journal of Medical Genetics ◽

10.1136/jmedgenet-2020-107604 ◽

2021 ◽

pp. jmedgenet-2020-107604

Author(s):

Paula Fernández-Álvarez ◽

Marta Codina-Sola ◽

Irene Valenzuela ◽

Gisela Teixidó-Turá ◽

Anna Cueto-González ◽

...

Keyword(s):

Marfan Syndrome ◽

De Novo ◽

Normal Population ◽

Genetic Disorders ◽

Somatic Mosaicism ◽

Clinical Signs ◽

Systematic Analysis ◽

Pathogenic Variants ◽

Fibrillin 1 ◽

Minor Criteria

BackgroundA proportion of de novo variants in patients affected by genetic disorders, particularly those with autosomal dominant (AD) inheritance, could be the consequence of somatic mosaicism in one of the progenitors. There is growing evidence that germline and somatic mosaicism are more common and play a greater role in genetic disorders than previously acknowledged. In Marfan syndrome (MFS), caused by pathogenic variants in the fibrillin-1 gene (FBN1) gene, approximately 25% of the disease-causing variants are reported as de novo. Only a few cases of parental mosaicism have been reported in MFS.MethodsEmploying an amplicon-based deep sequencing (ADS) method, we carried out a systematic analysis of 60 parents of 30 FBN1 positive, consecutive patients with MFS with an apparently de novo pathogenic variant.ResultsOut of the 60 parents studied (30 families), the majority (n=51, 85%) had a systemic score of 0, seven had a score of 1 and two a score of 2, all due to minor criteria common in the normal population. We detected two families with somatic mosaicism in one of the progenitors, with a rate of 6.6% (2/30) of apparently de novo cases.ConclusionsThe search for parental somatic mosaicism should be routinely implemented in de novo cases of MFS, to offer appropriate genetic and reproductive counselling as well as to reveal masked, isolated clinical signs of MFS in progenitors that may require specific follow-up.

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Marfan Syndrome with CRHD

Indian Journal of Cardiovascular Disease in Women WINCARS ◽

10.1055/s-0040-1708580 ◽

2020 ◽

Vol 5 (04) ◽

pp. 322-326

Author(s):

Shahood Ajaz Kakroo

Keyword(s):

Marfan Syndrome ◽

Autosomal Dominant ◽

Similar Case ◽

Extensive Search ◽

Organ Systems ◽

The Family ◽

Fibrillin 1 ◽

History Of ◽

Mode Of Inheritance ◽

Rheumatic Heart

AbstractMarfan syndrome (MFS) is an inheritable disorder caused by mutation of fibrillin-1 gene. It is the most common disorder among disorders of connective tissue. Its mode of inheritance is autosomal dominant. The reported prevalence of this disorder is one in three thousand (3000) to five (5000) thousand individuals. It presents with varied manifestation and different range of severity. The organ systems most commonly affected by this disorder include eyes, cardiovascular system, and musculoskeletal system.The other systems which may be affected include respiratory system, skin, and central nervous system. It is diagnosed with the help of revised Ghent score which includes a set of various diagnostic criteria which need to be fulfilled. MFS in this patient was diagnosed after the fulfillment of the revised Ghent score criteria, which included a positive history of MFS in the family and a systemic score of 8.In this case report, we are reporting a case of MFS which is unusual and remarkable in the sense that it is associated with chronic rheumatic heart disease (CRHD), and not the cardiovascular features which are usually present in cases of MFS. We tried to find a similar case if ever reported previously and, after extensive search, we could find only few cases13 14 15 of MFS which were associated with CRHD.

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‘The Stuff of Slow Constitution’: Reading Down Syndrome for Race, Disability, and the Timing that Makes Them So

Somatechnics ◽

10.3366/soma.2016.0193 ◽

2016 ◽

Vol 6 (2) ◽

pp. 235-248 ◽

Cited By ~ 2

Author(s):

Mel Y. Chen

Keyword(s):

Down Syndrome ◽

Trisomy 21 ◽

Historical Perspective ◽

Early History ◽

Present Moment ◽

History Of ◽

Living Being

In this paper I would like to bring into historical perspective the interrelation of several notions such as race and disability, which at the present moment seem to risk, especially in the fixing language of diversity, being institutionalised as orthogonal in nature to one another rather than co-constitutive. I bring these notions into historical clarity primarily through the early history of what is today known as Down Syndrome or Trisomy 21, but in 1866 was given the name ‘mongoloid idiocy’ by English physician John Langdon Down. In order to examine the complexity of these notions, I explore the idea of ‘slow’ populations in development, the idea of a material(ist) constitution of a living being, the ‘fit’ or aptness of environmental biochemistries broadly construed, and, finally, the germinal interarticulation of race and disability – an ensemble that continues to commutatively enflesh each of these notions in their turn.

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Faculty Opinions recommendation of A nonsense mutation in the fibrillin-1 gene of a Marfan syndrome patient induces NMD and disrupts an exonic splicing enhancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1008392.105207 ◽

2002 ◽

Author(s):

Lynne Maquat

Keyword(s):

Marfan Syndrome ◽

Nonsense Mutation ◽

Syndrome Patient ◽

Exonic Splicing Enhancer ◽

Fibrillin 1 ◽

Splicing Enhancer

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Characterization of Caenorhabditis elegans Homologs of the Down Syndrome Candidate Gene DYRK1A

Genetics ◽

10.1093/genetics/163.2.571 ◽

2003 ◽

Vol 163 (2) ◽

pp. 571-580 ◽

Cited By ~ 1

Author(s):

William B Raich ◽

Celine Moorman ◽

Clay O Lacefield ◽

Jonah Lehrer ◽

Dusan Bartsch ◽

...

Keyword(s):

Down Syndrome ◽

Caenorhabditis Elegans ◽

Trisomy 21 ◽

Gene Dosage ◽

Inducible Promoters ◽

C Elegans ◽

Dual Specificity ◽

Specificity Protein

Abstract The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.

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Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Genes ◽

10.3390/genes12020268 ◽

2021 ◽

Vol 12 (2) ◽

pp. 268

Author(s):

Marta Ferrari ◽

Stefano Stagi

Keyword(s):

Down Syndrome ◽

Autoimmune Diseases ◽

Normal Population ◽

Underlying Mechanism ◽

Short Review ◽

Immune Dysregulation ◽

Infectious Complications ◽

Genetic Syndromes ◽

Genetic Syndrome

Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes.

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