Marfan syndrome occurs in offspring of older fathers

Nigeria: Marfan Syndrome






COLUMN
11 May 2008
Posted to the web 12 May 2008

Lagos

Marfan Syndrome is an inherited connective tissue disorder where individuals are characteristically very tall, slender, have a narrow face, loose joints and associated spinal or chest wall abnormalities.

It is caused by a defect in the gene that enables the body to produce fibrillin which is a protein that helps give connective tissue its strength and elasticity. Most people with Marfan Syndrome inherit the abnormal gene from an affected parent passed on in an autosomal dominant fashion. Autosomal dominant means that only a defective gene from one parent is required to pass the disease on. Each child of an affected parent has a 50% chance of inheriting the defective gene. About 25% of cases are as a result of a mutation occurring for the first time in the egg or sperm of a parent that does not have Marfan Syndrome. The disorder affects connective tissue comprised of fibres that provide the framework and support for the body. Marfan syndrome affects many sytems in the body since connective tissue is widespread.


It may affect the blood vessels and heart, eyes, skeleton and skin. Severity of damage varies on an individual basis ranging from mild to severe. The most serious and potentially fatal effects of Marfan Syndrome involve the Aorta which is the large artery that carries blood from the heart to the rest of the body. The connective tissue in the walls of the aorta are weakened which may lead to enlargement, tear or rupture. Marfan Syndrome is a serious condition. Fortunately, advances in treatment, early diagnosis and close, careful management makes it possible for individuals to live full productive lives.

The signs and symptoms of Marfan Syndrome vary greatly because so many body systems are affected. Some individuals have mild symptoms while others have severe effects. In most cases the condition progresses and worsens with age. The most commonly seen traits and problems associated with Marfan Syndrome include the Physical Characteristics of Tall slender build, spidery fingers and toes (Arachnodactyly), and long arms and legs which are disproportionate to the rest of the body.

Individuals may also have Scoliosis (Curvature of the spine), Loose and excessively flexible joints, An abnormally shaped sternum (breastbone) which may protrude outward (pectus carinatum) or bend inward (pectus excavatum), A high arched palate and crowded teeth, Flat feet and a Narrow Face. In the majority of cases the Cardiovascular system (heart and blood vessels) are affected. This involvement is the most serious and accounts for the majority of Marfan related deaths. An aortic aneurysm may occur which is a bulge in the vessel. The aneurysm usually originates at the point where the aorta leaves the heart and it may extend to the abdominal portion of the aorta. Over a period of time constant pressure of the blood passing through this weakened vessel may cause the aneurysm to further enlarge. This enlargement may become more complicated leading to aortic dissection or rupture. Aortic rupture leads to life-threatening internal bleeding which requires immediate surgical intervention. The larger an aneurysm, the more likely the risk of dissection or rupture. Doctors check for aneurysms and monitor the size periodically.

A weakened enlarged aorta doesn't usually cause symptoms but breathlessness may occur if there is a leak of blood back into the heart. Aortic dissection however may cause a sudden, severe stabbing or ripping pain just under the sternum that radiates to the back. Less than half of individuals with Marfan Syndrome survive an Aortic dissection. Marfan syndrome may also affect the mitral valve of the heart causing it to prolapse. This is the valve on the left side of the heart that separates the left atrium from the left ventricle. In Marfan Syndrome the valve is long and floppy and as a result fails to close completely when the left ventricle contracts. This may lead to backflow (Mitral Regurgitation) and associated breathlessness, abnormal heart rhythms (arrhythmias), endocarditis (valve infection) and congestive heart failure.

Most individuals with Marfan Syndrome have problems with their eyes and vision. They often are nearsighted (Myopic), may have Dislocation or shifting of the lens in one or both eyes due to weak suspensory ligaments, Glaucoma (high pressure in the eye), Cataract (cloudy lens) and Retinal Detachment. Unusual bone growth and weak ligaments lead to problems such as scoliosis (curvature of the spine which may be "S" or "C" shaped), Spondylolisthesis where one spinal vertebra slips forward over another leading to back pain and stiffness and Foot Pain as a result of delicate feet. Individuals with Marfan Syndrome develop stretch marks because the skin lacks the proper connective tissue to keep it resilient. These marks usually develop over areas of stress such as the shoulders, hips and low back. Dural Ectasia describes the weakening and expansion of the Dura which is the membrane (composed of connective tissue) that encloses the brain and spinal cord.

With time the enlarged membrane may press on the lower vertebrae of the spine leading to low back pain

and possibly abdominal pain, headache and pain or numbness in the legs.

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Marfan syndrome is one of the most common of over 100 inherited connective tissue disorders. It affects men and women equally and it occurs in all races and ethnic groups. A team of specialists are usually required to evaluate and manage individuals with Marfan Syndrome. Specialists include Ophthalmologists, Orthopaedic Surgeons, Cardiologists and Medical Geneticists. Treatment is given based on signs, symptoms and presentation.

Clinical history, Family history, Physical examination and Medical investigations are required to make a diagnosis.

Women with aortic aneurysms are advised not to get pregnant because there is an increased risk of aortic dissection and rupture during pregnancy.

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http://en.wikipedia.org/wiki/Paternal_age_effect




The paternal age effect describes the influence that a father's age has on the chances of conferring a genetic defect to his offspring. Generally, older men have a greater probability of fathering children with a genetic defect than younger men do.[citation needed] This is seen as likely due to genetic copying errors which may increase in number after repeated spermatogenesis cycles over a man's lifetime.

Contents
1 Disorders correlated with paternal age
2 See also
3 References
4 External links


Disorders correlated with paternal age
Achondroplasia (dwarfism); craniofacial disorders such as Apert syndrome and Crouzon Syndrome; mental retardation of unknown etiologies; autism; and 25% of schizophrenia cases are correlated with advanced paternal age.

Other disorders related to advanced paternal age are:

Wilms' tumor
Thanatophoric dysplasia
Retinitis pigmentosa
Osteogenesis imperfecta type IIA
Acrodysostosis
Fibrodysplasia ossificans progressiva
Aniridia
Bilateral retinoblastoma
Multiple exostoses
Marfan Syndrome
Lesch-Nyhan syndrome
Pfeiffer Syndrome
Wardenburg Syndrome
Treacher-Collins Syndrome
Soto’s basal cell nevus
Cleidocranial dysostosis
Polyposis coli
Oculodentodigital syndrome
Costello syndrome
Progeria
Recklinghausen’s neurofibromatosis
Tuberous sclerosis
Polycystic kidney disease
Hemophilia A
Duchenne muscular dystrophy
Athetoid Cerebral Palsy
Dystonic Cerebral Palsy
Congenital Hemiplegia

[edit] See also
Maternal age effect

[edit] References
Crow JF (1997). "The high spontaneous mutation rate: Is it a health risk?". PNAS 94: 8380–6.
Bertram L, Busch R, Spiegl M, Lautenschlager NT, Müller U, Kurz A (1998). "Paternal age is a risk factor for Alzheimer disease in the absence of a major gene". Neuroscience 1 (4): 277–80.
Sipos A, Rasmussen F, Harrison G, Tynelius P, Lewis G, Leon DA, Gunnell D (2004). "Paternal age and schizophrenia: a population based (sic) cohort study". BMJ Online.
DNA repair activity linked to paternal age effect. University of Texas Health Science Center at San Antonio (2000-08-28).
Bray I, Gunnell D, Smith GD (2006). "Advanced paternal age: How old is too old?". Journal of Epidemiology and Community Health 60: 851–3.
Montgomery SM, Lambe M, Tomas O, Ekbom A (2004). "Paternal age, family size, and risk of multiple sclerosis". Epidemiology 15 (6): 717–23.
Reichenberg A, Gross R, Weiser M, Bresnahan M, Silverman J, Harlap S, Rabinowitz J, Shulman C, Malaspina D, Lubin G, Knobler HY, Davidson M, Susser E (2006). "Advancing paternal age and autism". Archives of General Psychiatry 63 (9): 1026–32.
Sanders L (2005). College scientist named Ellison Senior Scholar. University of Southern California College of Letters, Arts & Sciences.
Fisch H, Hyun G, Golden R, Hensle TW, Olsson CA, Liberson GL (2003). "The influence of paternal age on down syndrome (sic)". J Urol 169 (6): 2275–8. PMID 12771769.
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Lauritsen MB, Pedersen CB, Mortensen PB (2005). "Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study". J Child Psychol Psychiatry 46 (9): 963–71. PMID 16108999.
Wohl M, Gorwood P (2007). "Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring". Eur Psychiatry 22 (1): 22–6. PMID 17142012.
Schizophrenia Research Forum: Current Hypotheses (2006-03-28).
Choi J-Y, Lee K-M, Park SK, Noh D-Y, Ahn S-H, Yoo K-Y, Kang D (2005). "Association of paternal age at birth and the risk of breast cancer in offspring: a case control study". BMC Cancer 5: 143.
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Croen LA, Najjar DV, Fireman B, Grether JK (2007). "Maternal and paternal age and risk of autism spectrum disorders". Archives of Pediatrics and Adolescent Medicine 161 (4): 334–40.
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