Marfan Syndrome

Alternative Names

  • MFS
  • Marfan Syndrome, Type I
  • MFS1

Associated Genes

Fibrillin 1
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

OMIM Number

154700

Mode of Inheritance

Autosomal dominant

Gene Map Locus

15q21.1

Description

Marfan Syndrome (MFS) is an autosomal dominantly transmitted genetic disorder involving the connective tissue, characterized by arachnodactyly and cardiovascular abnormalities. The clinical spectrum of MFS is varied, ranging from asymptomatic condition to a severe state. Most commonly affected organs and organ systems include the skeletal system (long, slender, and loose jointed bones, scoliosis, pectus excavatum), eye (lens dislocation, retinal detachment, myopia, glaucoma, cataract, coloboma of iris), mouth and oral cavity (highly arched palate, crowded teeth, micrognathia) and nervous system (dural ectasia), among others. However, the most severe complications of the condition are its effects on the cardiovascular system. MFS causes the arterial walls to weaken, leading to its dilatation. Such a dilated artery can easily tear, lead to aortic dissection, and/or aneurysm. The aorta is fairly frequently affected. The heart valves may also be affected, especially the mitral and aortic valves causing blood to leak backwards through them. This may cause an enlargement of the heart, and/or mitral valve prolapse.

MFS is transmitted in an autosomal dominant manner. Interestingly, the disease is due to a single gene defect with full penetrance, although inter and intra familial variability is seen. About 75% of incidences of MFS is due to vertical transmission of a mutated gene, whereas the remaining is due to spontaneous mutations.

The causative gene is FBN1 (Fibrillin) gene, located on chromosome 15. This gene codes for the Fibrillin 1 glycoprotein, which plays an important role in the formation of the elastic fibers seen in connective tissues. When mutations are present in this gene, the protein may lose its function, thereby endangering the stability and support afforded by it, especially to the aorta, ligaments, and the eye.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
154700.1LebanonUnknown Tall stature... NM_000138.4:c.7713T>GHeterozygousAutosomal, DominantNair et al. 2018
154700.2Saudi ArabiaMaleNo Tall stature; Aortic dilatation; Dolicho... NM_000138.5:c.6872-1G>AHeterozygousAutosomal, DominantMaddirevula et al. 2018 De novo mutation
154700.3Saudi ArabiaFemaleNo Tall stature; Ectopia lentis; Myopia; He... NM_000138.5:c.2626_2634delHeterozygousAutosomal, DominantMaddirevula et al. 2018 De novo mutation

Other Reports

Kuwait

Marva (1998) reported Marfan's syndrome for the first time in a 23-year-old Arab man from Kuwait. The patient presented with unstable bladder, and medical check-up revealed a degree of mental deficiency. Additionally familial incidence of marfanoid and heart abnormalities was detected.

[Marva M. Non-immune hydrops associated with urogenital sinus. Med Princ Pract. 1998; 7(3):226-9.]

Lebanon

Mégarbané et al., 2020 described a patient with overlapping LDS5 and Marfan syndrome features, and a homozygous deletion of the genomic region encompassing exons 2-7 of the TGFB3 gene. Same mutation was identified in the patient’s phenotypically normal parents but in heterozygous state. The novel homozygous variant detected in the patient was predicted to disrupt the TGF-β signalling pathway and indicated an autosomal recessive mode of inheritance previously unreported among patients with TGFB3 variants.

Oman

Venugopalan et al. (1997) reported the skeletal, ophthalmic and cardiac features of Marfan's syndrome in a 10-year old Omani boy who was referred to them for cardiac evaluation. He had history of shortness of breath and palpitation while playing, but there was no family history of a similar condition. Examination revealed a long (height on the 75th percentile) and thin (weight on the third percentile) male with skeletal features of Marfan's syndrome which included long thin fingers, arm span of 150 cm (more than height by 6 cm), high arched palate, pectus excavatum, thoracic scoliosis, and hyperextensible joints. His ophthalmic features were bilateral upward displacement of the lens with left retinal detachment. On the other hand, cardiovascular examination revealed high volume and collapsing radial pulse with high pulse pressure, cardiomegaly with forceful cardiac apex, right ventricular hypertrophy as indicated by a grade 2/4 left parasternal heave, normal first and second heart sounds but audible third heart sound over the apex, and a grade 4/6 ejection systolic murmur over the left second and third intercostal spaces with early diastolic murmur. Other systemic examinations were normal, except for a palpable liver of two cm below the costal margin. Investigations revealed a metacarpal index of 10.8, consistent with the diagnosis of Marfan's syndrome. Investigations to evaluate the cardiac lesions confirmed cardiomegaly and showed prominent ascending aorta and aortic arch by chest X-ray. Electrocardiogram revealed left atrium enlargement and left ventricular hypertrophy. This was confirmed by echo Doppler studies, which also revealed aneurysmal dilatation of the aortic root (which appeared as a clover leaf on cross sectional study) and ascending aorta which was compressing on normal pulmonary arteries (maximum aortic diameter was 6.5 cm). The dilatation stopped just proximal to the origin of the right innominate artery with normal aortic arch and descending aorta. Other findings were early systolic partial closure of the aortic valve with paradoxical movement of the posterior aortic wall and severe aortic valve regurgitation (due to non coaptation of its leaflets), dilated proximal coronary arteries of 6mm and 5mm of the left and right arteries, respectively, and thickened and redundant mitral and tricuspid valves leaflets. Homocystinuria was excluded by urinary aminoacidogram. The parents were counseled on the condition and cardiac catheter studies, angiography and surgical correction of the cardiac lesions were advised, but they declined any surgical intervention.

[Venugopalan P, Akinbami FO, Elnour IB. Cardiovascular manifestations of Marfan's syndrome a case report with review of literature. Oman Med J. 1997; 14(2):46-9.]

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