Marfan Syndrome: Why The Long Face?

Achondroplasia is when cartilage during development is not developed into bone, which results in dwarfism. This condition also characterized by short limbs is initiated by a gain of function mutation in the FGFR3 gene. This mutation is a point mutation. When this mutation occurs, the receptor of the FGF does not need the FGF signal to be activated. This causes the chondrocytes to stop dividing and start differentiating into cartilage prematurely and the bones fail to grow to their proper length, thus resulting in the short limbs that result from this mutation. (textbook) The FGFR3 gene encodes for the Fibroblast growth factor receptor 3 protein. Textbook

Autosomal dominant LGMD occur less often than recessive dominant LGMD. In the metabolism myotilin gene mutations occur, it may be due to a deficiency of vitamin B12, vitamin E, folate or exposures to nitrous oxide. LGMD 1A disease normally occurs from the age 42 to 77, and develops in the same areas (hip, shoulder and back) however, it could spread to the leg muscles. Due to the fact that myotilin gene is mutated, it causes focal myofibrillar destruction to occur, and this results in intracytoplasmic deposits to float around in the blood stream. In one case study done in Barcelona in 2011, there were 13 patients who were all diagnosed with myotilin gene mutation disease. The results showed that the deposits of myofibrillar became immune to myotilin and cluster up the vacuoles and interfere with the Z-lines. Overall the study revealed that each patient shared the same phenotypic characteristics, LGMD 1A and myofibrillar myopathy variations which emphasizes that LGMD is a developing neuromuscular disorder (Montse,

Marfan syndrome is a genetic mutation of the FBN1 gene which codes for a protein that contributes to the connective tissue in the body and releases certain growth hormones (Callewaert et al., 2007). A mutation in this gene contributes to a variety of signs and symptoms usually involving skeletal deformations like long bone overgrowth, causing elongated limbs and spinal conditions like scoliosis and kyphosis (Callewaert et al., 2007). Retina detachment is common in those with Marfan syndrome and cardiovascular complications may include aortic dilation, dissection and rupture and up two thirds of patients develop mitral valve dysfunction (Callewaert et al., 2007). R.C. has experienced detached retinas,

Week five I wrote about a sperm bank that lost a deceased man's vials of sperm. Grief, sorrow, and suffering were all feelings felt by Sarah Robertson after the loss of her 29 year-old husband, Aaron Robertson. Aaron had passed away from a rare genetic disorder known as Marfan Syndrome. Sarah mourned the death of her husband, but had somewhat comfort in knowing that six vials of her deceased husbands sperm were safely stored at the Reproductive Fertility Center in Los Angeles. As time went on since Aaron passed, Sarah felt she was ready to put his vials of sperm to use. Devastating news awaited Sarah as she was told that all six vials had been reported missing. Sarah and her in-laws are suing the LA clinic and Dr. Peyman Saadat, the owner.

Myopia (nearsightedness) is one of the most common symptoms of the disease. Other symptoms occurring in the eyes include dislocated lens, detached retina, risk of early glaucoma and/or cataracts, and, if not treated, can result in vision loss. Symptoms of the cardiovascular system include a stretched or weakened aorta (aortic dilation or aneurysm) due to defective connective tissue and defects in heart valves. An example of a valve defect is mitral valve prolapse in which one or both cusps of the mitral valve swells or collapses into the left upper atrium when the heart contracts. Cardiovascular symptoms can lead to arrhythmias, congestive heart failure, and chest pain. There are also some effects on lungs, albeit not as common as other symptoms, in which the air sacs can become stretched and lead to an increased risk of lung collapse. The nervous system is also affected as dural ectasia, where the dura that covers the spinal fluid stretches and weakens, eventually leading the bones of the spinal column to wear away. Other symptoms are more obvious and affect the skeletal and connective tissue systems. Those with Marfan syndrome commonly have stretch marks and overgrowth of the

Hutchinson-Gilford Progeria Syndrome (HGPS) affects approximately 1 in 4-8 million newborns. It is characterized by rapid aging, but no symptoms are seen at birth. Within a year, infected children start showing symptoms such as a receding jaw, pointy nose, partial to total hair loss (alopecia), fat loss, bone disfigurements, a short stature and skin problems (Pollex 2004). The disease progresses with time, and eventually leads to death at an average age of about 13 years. Death is usually caused by some form of cardiovascular disease, usually induced by atherosclerosis (Wuyts et al. 2005). Most cases of HGPS are due to de novo autosomal dominant point mutations in the lamin A/C gene (LMNA). There are some reported cases suggesting autosomal recessive inheritance, but further testing needs to be performed.

The condition presents itself congenitally. Cardiofaciocutaneous syndrome is a diversified congenital abnormality disorder that has numerous amounts of obvious symptoms. Individuals in possession of this disorder have oddities in their facial features, skin and hair, heart, digestive system, growth, and intellectual ability. Typically, they have a large forehead and head, a concave nasal arch, and droopy wide-spaced eyes. This causes them to be astigmatic and have skittish eyes, which can possibly result in abated eyesight and awareness. Their skin awfully lacks moisture and is quite thick. They have very little curly and brittle hair on their head. They also may not have, or only have very little, eyelashes or eyebrows.

Researchers believe the mutation of this gene causes too much bone to grow instead of muscle.

The purpose of this paper is to discuss the effects of the disorder and how genetics and biochemistry work together to create this

(Giarelli, Bernhardt, & Pyeritz, 2010, Lashley, 2007 ,Canadas et al., 2010). The mutant gene is found on an autosome consequently, the syndrome can affect males and females equally. While, only one copy of the mutant gene is necessary for the disorder to be present (Lashley, 2007). Fibrillin-1 is a large gene, made of complex glycoproteins that are responsible for the flexibility and strength of connective tissue (Giarelli, Bernhardt, & Pyeritz, 2010 & Gonzales, 2009). Fibrillin-1(FBN1) is most abundant in the cardiac, ocular and, skeletal system throughout the body. This glycoprotein can also be found in elastic and non- elastic tissues and is a chief component of microfibrils. Microfibrils maintain cellular bonds in the extracellular matrix and form the framework of elastic fibers in the aorta and ligaments of the musculoskeletal system and multiple organ systems (Keane & Pyeritz, 2008). These microfibrils consist of the structural parts that support the ligaments in the ocular lens and have a load-bearing role in elastic arteries (Chen & Buehler, 2010). As a result of the mutation in the FBN1 gene abnormalities occur in the microfibrils and can cause faulty connective tissue. The mutations were thought to create weakness of the aortic wall, lens dislocation, joint hyperlaxity and, widening

Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal dominant disorder caused by germline mutations in the folliculin (FLCN) gene (Nookala et al., 2012; Nickerson et al., 2008; Menko et al., 2012; Hartman et a., 2009). Patients with BHD initially develop fibrofolliculomas, typically as benign facial tumors, and lung cysts; whereby, increasing their risk to develop renal cell carcinoma (RCC) and pneumothorax (Nookala et a., 2012; Menko et al., 2012; Hartman et al., 2009). The majority of the BHD patient population contain germline mutations in FLCN exon 11, which is a hotspot for disease causing mutations. BHD research predicts mutations in FLCN results in a truncated folliculin protein lacking its c-terminal end, thus, suggestion the

Although folliculin function is speculative, its highly conserved. FLCN gene contains 14 exons and exon 11 is constituted as a mutational hotspot due to the majority BHD patient population contain mutations in this exon. As many as 84 variants in the folliculin gene are reported to cause BHD by which majority of the mutations cause FLCN truncation deletion (Hasumi et al., 2008). FLCN protein structure and

     Recent studies show that this syndrome may be associated with changing craniofacial and skeletal muscle metabolism, such as blood flow, which causes the chronic fatigue and severe weakness. Another hypothesis is that an infectious trauma to the body, such as a virus, triggers the illness. However, with this syndrome being new, no specific virus has been identified. There is though a plot study that shows that there is possible inherited tendency toward the disease. This disease/syndrome has increased

Collagen is responsible for giving strength and structure to skin, bone, blood vessels, and other internal organs. It affects about 1 in 5,000 people. This disorder is usually, but not always, dominant. Some types of the 11 types of EDS are dominant and some are recessive. This Punnett square diagram demonstrates the heredity of the syndrome.

Neurofibromatosis type one or NF1 is caused by a genetic mutation. A genetic mutation is a permanent change in the DNA sequence that makes up a gene. In half of the cases where people