Syndromes

Down syndrome Down syndrome or trisomy 21 is a genetic disorder caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British doctor who first described it in 1866. The condition is characterized by a combination of major and minor differences in body structure. Often Down syndrome is associated with some impairment of cognitive ability and physical growth as well as facial appearance. Down syndrome is usually identified at birth.

Effects 

Individuals with Down syndrome may have some or all of the following physical characteristics: oblique eye fissures with epicanthic skin folds on the inner corner of the eyes, muscle hypotonia (poor muscle tone), a flat nasal bridge, a single palmar fold (also known as a simian crease), a protruding tongue (due to small oral cavity, and an enlarged tongue near the tonsils), a short neck, white spots on the iris known as Brushfield spots, excessive flexibility in joints, congenital heart defects, excessive space between large toe and second toe, a single flexion furrow of the fifth finger, and a higher number of ulnar loop dermatoglyphs. Most individuals with Down syndrome have mental retardation in the mild (IQ 50–70) to moderate (IQ 35–50) range, with scores of children having Mosaic Down syndrome (explained below) typically 10–30 points higher. In addition, individuals with Down syndrome can have serious abnormalities affecting any body system.

Genetics 

Down syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the 21st chromosome, either in whole (trisomy 21) or part (such as due to translocations).

Klinefelter's syndrome • Klinefelter's syndrome, 47,XXY or XXY

syndrome is a condition caused by a chromosome nondisjunction in males; affected individuals have a pair of X sex chromosomes instead of just one and are at additional risk for some medical conditions. It is named after Dr. Harry Klinefelter, a medical researcher at Massachusetts General Hospital, Boston, Massachusetts, who first described this condition in 1942. The condition exists in roughly 1 out of every 500 males.

Signs and symptoms • Affected males are almost always sterile, and some degree

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of language impairment may be present. In adults, possible characteristics vary widely and include little to no signs of affectedness, a lanky, youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue). Gynecomastia to some extent is present in about a third of individuals affected, a higher percentage than in the XY population. The far end of the spectrum is also associated with an increased risk of breast cancer, pulmonary disease, varicose veins, diabetes mellitus, rheumatoid arthritis, and osteoporosis, risks shared with women. Rare X-linked recessive problems occur even more infrequently in XXY males, since these conditions are transmitted by genes on the X chromosome, and people with two X chromosomes are typically carriers rather than affected

Cause • The XXY chromosome arrangement is one of the

most common genetic variations from the XY karyotype, occurring in about 1 in 500 live male births. Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47,XXY Males" rather than as "suffering from Klinefelter's syndrome."

Leber' s he redi tary op tic neuropathy •

Le be r’s he redi tar y op tic ne urop athy (LH ON) or Le be r op tic at roph y is a mitochondrially inherited (mother to all offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males. However, LHON is only transmitted through the mother as it is primarily due to mutations in the mitochondrial (not nuclear) genome and only the egg contributes mitochondria to the embryo. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations affect nucleotide positions 11778, 3460 and 14484, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria. Men cannot pass on the disease to their offspring

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Signs & symptoms • Clinically, there is an acute onset of visual loss, first in one, eye and then a few weeks later in the other. This eventually evolves to very severe optic atrophy and permanent decrease of visual acuity. In the acute stage lasting a few weeks, the affected eye demonstrates an edematous appearance of the nerve fiber layer especially in the arcuate bundles and enlarged or telangectatic and tortuous peripapillary vessels (microangiopathy). These main features are seen on, fundus examination just before or subsequent to the onset of visual loss. Examination reveals decreased visual acuity, loss of color vision and a cecocentral scotoma on visual field examination.

Genetic s • Leber hereditary optic neuropathy is a condition related to changes in mitochondrial DNA. Although most DNA is packaged in chromosomes within the nucleus, mitochondria have a distinct mitochondrial genome composed of mtDNA

Muscular dystrophy Muscular dystrophy is a genetic condition that describes more than 30 genetic and hereditary muscle diseases. Of these 30, nine types are formally declared to be Muscular Dystrophy and the remaining are generally classified as muscular dystrophy. Muscular Dystrophy is characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue . In some forms of muscular dystrophy, cardiac and smooth muscles are affected. Muscular dystrophy is the most well known of hereditary diseases

Genetic cause These conditions are inherited, and the different muscular dystrophies follow various inheritance patterns. The most well-known type, Duchenne muscular dystrophy (DMD), is inherited in an X-linked recessive pattern, meaning that the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes, and is thus considered sex-linked. In males (who have only one X chromosome) one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes) a mutation must generally be present in both copies of the gene to cause the disorder (relatively rare exceptions, manifesting carriers, do occur due to dosage compensation/X-inactivation). Males are therefore affected by X-linked recessive disorders much more often than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Symptoms Principal symptoms include but are not limited to: Progressive Muscle Wasting Weakness Loss of Function in Muscle Skills Poor Balance Frequent Falls Walking Difficulty Waddling Gait Calf Pain Limited Range of Movement Joint Contractures Cataracts Frontal Baldness Drooping Eyelids (ptosis) Drooling Gonadal Atrophy Mental Impairment (with myotonic dystrophy) Scoliosis (curved spine

Diagnosis The diagnosis of muscular dystrophy is based on the results of a muscle biopsy. In some cases, a DNA blood test may be all that is needed. A physical examination and the patient's medical history will help the doctor determine the type of muscular dystrophy. Specific muscle groups are affected by different types of muscular dystrophy.

Treatment There is no known cure for muscular dystrophy. Inactivity (such as bed-rest and even sitting for long periods) can worsen the disease. Physical therapy and orthopedic instruments (e.g., wheelchairs, standing frames) may be helpful

Tay-Sachs disease 

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Tay-Sachs disease (abbreviated TSD, also known as "GM2 gangliosidosis") is a genetic disorder, fatal in its most common variant known as Infantile Tay-Sachs disease. TSD is inherited in an autosomal recessive pattern. The disease occurs when harmful quantities of a fatty acid derivative called a ganglioside accumulate in the nerve cells of the brain. Gangliosides are lipids, components of cellular membranes, and the ganglioside GM2, implicated in Tay-Sachs disease, is especially common in the nervous tissue of the brain. The disease is named after the British ophthalmologist Warren Tay who first described the red spot on the retina of the eye in 1881

Spinal muscular atrophy 

Spinal Muscular Atrophy (SMA) is a term applied to a number of different disorders, all having in common a genetic cause and the manifestation of weakness due to loss of the motor neurons of the spinal cord and brainstem

Symptoms          

Infantile SMA is the most severe form. Some of the symptoms include: muscle weakness poor muscle tone weak cry limpness difficulty swallowing the legs tend to be weaker than the arms feeding difficulties increased susceptibility to respiratory tract infections developmental milestones, such as lifting the head or sitting up, can't be reached

Cause 

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The region of chromosome 5 that contains the SMN (Survival Motor Neuron) gene has a large duplication. A large sequence that contains several genes occurs twice in adjacent segments. There are thus two copies of the gene, SMN1 and SMN2. The SMN2 gene has an additional mutation that makes it less efficient at making protein, though it does so in a low level. SMA is caused by loss of the SMN1 gene from both chromosomes. The severity of SMA, ranging from SMA 1 to SMA 3, is partly related to how well the remaining SMN 2 genes can make up for the loss of SMN 1. Often there are additional copies of SMN2, and an increasing number of SMN2 copies causes less severe disease. All forms of SMN-associated SMA have a combined incidence of about 1 in 6,000. SMA is the most common cause of genetically determined neonatal death. The gene frequency is thus around 1:80, and approximately one in 40 persons are carriers. There are no known health consequences of being a carrier, and the only way one might know to consider the possibility is if a relative is affected