Timothy syndrome is a rare autosomal dominant disorder which is characterized by physical malformation as well as neurological and developmental defects. This includes heart QT prolongation, heart arrhythmias, structural heart defects, syndactyly which is the webbing of fingers and toes and also autism spectrum disorder.

It is really quiet sad to note but it is a truth that the timothy syndrome often ends with the death of the victim.

Symptoms

As far as the most striking sign of Timothy syndrome is concerned it is really marked by the co-occurrence of both syndactyly (~0.03% of births) and long QT syndrome (1% per year) in a single patient. These are just not only the two symptoms of the timothy syndrome. Some other common symptoms of Timothy syndrome are cardiac arrhythmia (94%), heart malformations (59%), autism or an autism spectrum disorder.

The Facial dysmorphologies is also quiet common. I really feel that you would definitely like to know about what this really is? I must tell you that the facial dysmorpholgies is marked by flattened noses and it also occurs in approximately half of patients. Children who are suffering from this kind of disorder have small teeth which, due to poor enamel coating, are prone to dental cavities and often require removal. You should also know that the average age of death due to complications of these symptoms is 2.5 years.

It has really been found that Atypical Timothy syndrome has largely the same symptoms as the classical form. If you will talk about the differences then I must tell you that the atypical form suffers from the lack of syndactyly, the presence of musculoskeletal problems, and atrial fibrillation. Patients with atypical Timothy syndrome also have more facial deformities, including stick out foreheads and tongues. Finally, one patient with atypical Timothy syndrome also suffers from the body development discrepancy. I saw one girl suffering from this disease and I found out that her upper body was normally developed (that of a 6-year-old) while her lower half resembled a 2- or 3-year-old.

Children who are suffering from Timothy syndrome tend to be born via caesarean section due to fetal distress.

Treatment

I do feel that the Surgery can be typically used to correct structural heart defects and syndactyly and in fact it is used as well. Doctors often prescribe the Propanolol or beta-adrenergic blockers as well as they do ask for the insertion of a pacemaker to maintain proper heart rhythm. Now after the characterization of Timothy syndrome mutations it has been indicated that they cause defects in calcium currents and hence it has been suggested by many doctors that calcium channel blockers may be effective as a therapeutic agent and also a good tactic to cure this disease.

Cornelia de Lange Syndrome is a little known genetic disorder which can lead to severe developmental anomalies and the problem really is that you will not be able to catch it because not much is known about this kind of the genetic disorder. It is really dangerous as it affects both the physical as well as the intellectual or mental development of the child. The Exact occurrence is unknown, but it is really estimated that you can find this disease among at least 1 in every 10,000 to 30,000.

Causes
A gene responsible for this disease is the NIPBL on Chromosome 5 and it was discovered in the year 2004 by some of the researchers who were doing their research at Children’s Hospital of Philadelphia. In 2006, a second gene which was SMC1A on the X chromosome was finally discovered by some of the Italian scientists. The third gene as well was discovered and the discovery was announced in the year 2007.  There was one another gene SMC3 which was discovered on chromosome 10 and it was also discovered by the research team in Philadelphia. The latter two genes were really correlating with the milder form of the syndrome.

All the researchers who were involved in this research really have the feeling that the vast majority of cases are due to spontaneous mutations, however you cannot say that the defected gene comes from the father or only the mother. The patient can really inherit this defected gene from either of their parents making it autosomal dominant.

I do feel that the first ever documented case was detected in the year 1916 by the W. Brachmann which is followed up by the Cornelia de Lange who was a Dutch pediatrician in 1933. As you are seeing, this disease was really named after this Dutch pediatrician.

Characteristic
Following are the characteristic of this disease:

1. Low birth weight (usually under 5 pounds / 2.5 kilograms).
2. Delayed growth and small stature.
3. Developmental delay.
4. Missing limbs or portions of limbs.
5. Microcephaly.
6. Thick eyebrows, which typically meet at midline.
7. Long eyelashes.
8. Short upturned nose and thin downturned lips.
9. Long philtrum.
10. Excessive body hair.
11. Small hands and feet.
12. Small widely spaced teeth.
13. Low-set ears.
14. Hearing impairments.
15. Vision abnormalities.
16. Partial joining of the second and third toes.
17. Incurved 5th fingers.
18. Gastro esophageal reflux.
19. Seizures.
20. Heart defects.

Treatment
I really feel that a team for endorsement of the child’s well being often includes speech, occupational and physical therapists, teachers, physicians, and most importantly the parent(s). However the exact and the complete description of this disease are still not known.

The research is really on and I do feel that we will soon find the exact solution of this disease.

Jervell and Lange-Nielsen syndrome refers to a kind of long QT syndrome. Now, long QT syndrome or LQTS, as it is most commonly known as, refers to an unusual congenital heart condition, which is characterized by delayed re-polarization subsequent to depolarization of the heart, related to fainting as a result of ventricular arrhythmias that can get deteriorated into ventricular fibrillation. This might ultimately result in sudden death.

As it is, Jervell and Lange-Nielsen syndrome results in the cardiac muscles taking up longer than usual time for recharging between the beats. In case if left untreated, the irregular heartbeats, might lead to seizures, fainting, or even sudden death. Jervell and Lange-Nielsen syndrome may also result in loss of hearing. As it is, such irregular heartbeats are referred to as arrhythmia. Cardiac arrhythmia or dysrhythmia refers to any of the large and heterogeneous set of conditions wherein there is an abnormal electrical activity of the heart. This might be characterized by a heart beat that might be too slow or too fast and may be irregular or regular.

In some cases, arrhythmias may prove to be life-threatening medical emergencies, which might cause cardiac arrest, as well as sudden death. In other cases, they result in aggravating symptoms like an abnormal awareness of the heart beat and might be merely annoying. In certain cases, symptoms may not at all be present, but result in potentially life threatening embolus or stroke.

In some cases, arrhythmias can be very minor and might be considered to be normal variants. As a matter of fact, many times people would sometimes feel that their heart skipped a beat, or at times, give a rare extra strong beat. Such a condition is referred to as an autosomal recessive disorder, which is responsible for a little less than one out of ten of all cases of long QT syndrome.

As it is, Jervell and Lange-Nielsen syndrome is caused due to mutations in the KCNQ1and KCNE1 genes. The proteins which are produced by these genes work together in order to form a potassium channel, which is used for channelizes the positively charged potassium ions out of cells. It is this movement of the potassium ions via these channels, which is very much critical for the maintenance of the normal functioning of the inner ear, as well as the cardiac muscle.

Mutations in the KCNQ1 gene contribute to around nine out of ten cases of Jervell and Lange-Nielsen syndrome. The remaining ten percent of the cases are caused due to KCNE1 mutations. Mutations in these two genes are responsible for the alteration in the usual structure, as well as the functioning of the potassium channels, in order to prevent the assembly of the normal channels. Now, these changes hamper the flow of potassium ions to the inner ear, as well as the cardiac muscles.

The Bardet-Biedl syndrome is a kind of ciliopathic human genetic disorder and I must tell you that it produces many effects and affects many body systems. As far as its characterization is concerned I must tell you that it is characterized principally by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.

Classification
The Bardet-beidl syndrome has bee given this name after the name of the two great scientists who were able to describe this disease and their name was Georges Bardet and Arthur Biedl.

As far as its classification is concerned I must tell you that the two forms have been identified up till now:

1. The first one is the Bardet-Biedl syndrome 1 which is abbreviated as BBS1 and is mapped to markers on chromosome 11.
2. The second one is the Bardet-Biedl syndrome 2 which is abbreviated as BBS2 and is mapped to markers on chromosome 16.

This disease is not a new one. I must tell you that this disease is quiet an old one and the first known case was reported by Laurence and Moon in 1866 at the Ophthalmic Hospital in South London. However it is quiet worthy to note that the Laurence-Moon-Biedl-Bardet syndrome are no longer considered as valid terms since the patients of Laurence and Moon had paraplegia but no polydactyly and obesity and you should know that these are the key elements of the Bardet-Biedl the syndrome.  Laurence-Moon syndrome is really the separate and almost different entity.

However, some recent research really says the different story. I must tell you that the recent researches are really giving the indication that both these type of the syndromes are really similar and we cannot really say that they are different from each other.

Major Clinical features

1. Eyes: Pigmentary retinopathy, poor visual acuity, low vision, and/or blindness caused by an impaired photoreceptor transport mechanism in the retina.
2. Nose: Loss of, or reduced sense of, smell (anosmia). Some patients claim extra-sensitive sense of smell.
3. Hand and foot: Polydactyly (extra digits) or syndactyly (webbing of fingers and toes).
4. Cardiovascular system: Hypertrophy of interventricular septum and left ventricle and dilated cardiomyopathy.
5. Gastrointestinal system: Fibrosis.
6. Urogenital system: Hypogonadism, renal failure, urogenital sinuses, ectopic urethra, uterus duplex, septate vagina, and hypoplasia of the uterus, ovaries, and fallopian tubes.
7. Growth and development: Mental and growth retardation.
8. As far as the behavior and the responses are concerned I must tell you that a wide variety of socialization and social interaction problems have been identified with BBS. Some doctors refer to it as a kind of “mild-Autism.”

I do feel that this disease is still incurable but we will soon find some solution to this disease.

Syringomyelia is a generic term, which refers to a disorder characterized by a cyst or cavity formation within the spinal cord. This cyst, which is known as syrinx, can expand and extend over time, damaging the spinal cord. Now, since the spinal cord connects the brain to nerves, such damage may cause pain, weakness, as well as stiffness in the back, arms, shoulders, as well as the legs.

Syringomyelia may also result in a loss of the ability to feel extremes of high or low temperature, especially in the hands. Each patient faces a different set of symptoms. Such symptoms usually differ in accordance with the extent and most of the time on the location of the syrinx within the spinal cord.

Diagnosis used to be difficult in the past, as the early symptoms of syringomyelia, were quite common to other, more common disorders. However, with the arrival of MRI, diagnosis of this condition has become much more accurate and timely. In fact, it has substantially improved the number of syringomyelia cases, which have been diagnosed in the beginning stages of the disorder.

As it is, symptoms of this disorder tend to evolve slowly, although sudden onset might occur, with signs like straining, coughing, as well as myelopathy. If not treated on time, syringomyelia might cause loss of sensation, progressive weakness in the extremities, chronic pain and even potentially total paralysis.

As it is, syringomyelia can be categorized under two major categories, which are as follows:

1. The first major category is associated with an abnormality of the brain, which is known as Arnold-Chiari malformation and is the most visible cause of syringomyelia. In this case, the anatomic abnormality results in the lower part of the cerebellum to bulge out from its usual location in the back of the head into the cervical position of the spinal canal. A syrinx may then evolve in the cervical area of the spinal cord.
2. The second major category of syringomyelia might develop due to complication of hemorrhage, trauma, meningitis, tumor, as well as arachnoiditis. In such a situation, the syrinx develops in a section of the spinal cord, which has been damaged by one of these conditions. The syrinx thereby begins to expand. This is also known as noncommunicating syringomyelia. As it is, symptoms might appear a long time after the initial injury and would usually be marked by pain, weakness, as well as sensory impairment.

Syringomyelia results in a wide variety of neuropathic symptoms, caused due to damage to the spinal cord. The patients might experience abnormal sensations, chronic pain and at times, loss of sensation particularly in the hands. In some cases, patients experience paralysis, as well as paresis, temporarily or at times permanently.

Sotos syndrome which is also known as cerebral gigantism is a rare genetic disorder which is characterized by excessive physical growth during the first 2 to 3 years of life. This disorder might lead to or may be accompanied by mild mental retardation, delayed motor, cognitive, and social development, hypotonia (low muscle tone), and speech impairments.

Children who are affected by the Sotos syndrome often tend to be of larger size at birth and in most of the cases are taller, heavier, and have larger heads. You should know that the disease in which the new born babies have larger head is called macrocrania and they really have much larger head which is quiet large as compared to the normal size for their age.

Symptoms of the disorder, which vary among individuals, include a disportionately large and long head with a slightly protrusive forehead, large hands and feet, hypertelorism which is an abnormally increased distance between the eyes, and also down slanting eyes.

The patients can also suffer from the Clumsiness, an awkward gait, and I do feel that the unusual aggressiveness or irritability can also be dominant among these patients. Although most cases of Sotos syndrome occur infrequently, familial cases have also been reported.

Symptoms
This disease is characterized by overgrowth and advanced bone age. Those individuals who are suffering from this disease are dysmorphic with macrodolichocephaly, down slanting palpebral fissures and a pointed chin. In childhood of such patient I do feel that the facial appearance is really one of the most important and notable. Those infants and the children who are suffering from this disease tend to grow quiet quickly. They are often found to be taller than their siblings and peers and they have quiet a larger head which is really unusual and the size is really more that what it should really be for that age. However, the Adult height is usually in the normal range.

People who are suffering from the Sotos syndrome often suffers from intellectual impairment and most of them have behavioral problems. As far as the frequent behavioral issues are concerned, it’s really good to know that this include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. This kind of patients do faces some problems as far as the speech and language are concerned. It is also quiet worthy to note that the affected individuals often have problems with sound production, stuttering, and a monotone voice. The individuals also suffer from the hypotonia which is often characterized by the weak muscle tone. This may too delay other aspects of early development, particularly motor skills such as sitting and crawling.

Treatment
This disease is still not fully treatable and the research is still on.

I do feel we will soon get the solution for this disease. However it is quiet good to stay away from this disease.

Spina bifida syndrome refers to a medical condition, which is denoted by a situation, where a part of the spinal cord is open at the time of birth. Spina bifida syndrome is a neural tube defect, which occurs at the time, when the fetus is growing inside the womb. At this stage, the spine of the baby does not develop correctly. As it is, a few vertebrae fail to close in to form their normal ring shapes around the spinal cord, causing this medical condition, which is known as Spina bifida syndrome.

More than ninety percent of infants born with spina bifida do not have any family history of it. However, in case if a mother has given birth to a child with spina bifida, the risk of prevalence of such a condition, occurring again in subsequent pregnancy increases manifold. In the U.S., spina bifida has been found to be more common among Hispanics and whites of European extraction, whereas, it has been found to occur less commonly among Asians, as well as African-Americans.

As it is, deficiency of folic acid in the mother is said to be associated with the occurrence of spina bifida in the infant. In order to reduce the chance of occurrence of spina bifida, the Food and Drug Administration Department has made it mandatory that all the enriched cereal grain products should be fortified with folic acid. This step has been quite helpful in this regard and has greatly reduced the occurrence of Spina bifida syndrome.

As it is, spina bifida syndrome can be categorized under three categories:
Spina bifida occulta: This is a condition, marked by a tiny opening, usually causes mild or no symptoms as such.
Spina bifida cystica - meningocele: This is a condition, which is marked by a big enough opening that causes, some of the membrane surrounding the spinal cord to stick out through the opening.
Spina bifida cystica - myelomeningocele: This is the third category and is the most serious kind. This condition is characterized by a situation, where some of the spinal cord itself sticks out through the opening in the spine.

A sad aspect in this regard is that, there is as such, no complete cure for spina bifida. As it is, the opening inside the spine can be sealed surgically either before or after birth. This reduces its effects on the body. Since, spina bifida results in trauma to the spinal cord, therefore treatment focuses on addressing the symptoms of the patient. This includes symptoms, like difficulty in standing, walking, or urinating.

The life expectancy of the children with spina bifida has increased by a large margin in the last few years. As it is, nowadays, around three fourths of children born with severe form of spina bifida syndrome are most likely to live until their early adult years.

Bloom syndrome refers to an autosomal recessive chromosomal disorder, which is characterized with high frequency of breaks, as well as changes in the chromosomes of an affected person. It is a very rare condition and was first addressed and explained by Dr. David Bloom, who was a well known dermatologist in the year 1954.

Also known as Bloom-Torre-Machacek syndrome, Bloom syndrome is characterized by a short stature along with facial rashes which appear shortly after the first exposure to sunlight. These rashes can take the form of large patches of reddened skin, appearing on the cheeks. They can also appear on other areas exposed to the sun, like the backs of the hands.

Apart from these, a person with Bloom syndrome might show features like a long, narrow face, smaller lower jaws, a high-pitched voice, prominent nose and ears, along with telangiectasias on the skin, as well as the eyes. This includes hypo-, as well as hyper-pigmented areas. Apart from that, other symptoms like other pigmentation alterations of the skin, moderate immune deficiency, causing recurrent pneumonia along with ear infections, as well as hypo-gonadism causing failure in the production of sperm, resulting in infertility in case of males and premature end of menses, thereby causing sub-fertility in case of females.

Further, the disorder may lead to serious problems like learning disabilities, chronic lung problems, as well as diabetes. In a few cases, it may also result in mental retardation. As it is, the most important factor related to this disorder is its receptiveness to cancer.

Bloom syndrome is associated with the mutations of the BLM gene, a member of DNA helicase family. As it is, DNA helicases are the enzymes, which unwind two strands of duplex DNA molecule. This DNA unwinding is necessary for most of the processes, which involve this DNA, such as RNA transcription, synthesis of DNA copies, DNA repair, etc.

Bloom syndrome gets transferred in an autosomal recessive pattern. This means that, both parents need to be carriers so as to pass the disorder to their child. People suffering from Bloom syndrome feature a major increase in the exchange events in between the homologous chromosomes. Two DNA molecules are produced by way of DNA replication. As it is, there is an increase in the chromosome breakage, along with changes. The relationships between the molecular defects in the Bloom syndrome cells, the mutations in chromosome, which appear in somatic cells, as well as the several clinical features visible in the syndrome, are also subjects of intense research.

The cerebral cortex denotes a structure located inside the brain. It plays a very vital role in various functions of the brain, such as perceptual awareness, consciousness, attention, language, thought, as well as memory. The outermost layer of the cerebrum is formed by neurons, along with their unmyelinated fibers, while the white matter below this layer of the cortex is formed primarily by myelinated axons interlinking the different areas of the central nervous system. The human cerebral cortex has found to be around 2-4 mm thick.

The cerebral cortex evolves from the most frontal part of the neural plate, which is an important part of the embryonic ectoderm. The neural plate is in folded shape, to form the neural tube. The ventricular system develops from the cavity located in the neural tube. Similarly, the neurons, as well as the glia of the nervous system, develop from the epithelial cells of its walls. The most frontal part of the neural tube, i.e. the telencephalon, makes way for the cerebral hemispheres and the cortex.

The exterior of the cerebral cortex has been found to be wrinkled in case of large mammals in such a way, that more than two third of the cortical surface is covered inside the grooves, known as sulci. The most recently developed part of the cerebral cortex, i.e. the neocortex, can be divided into six horizontal layers, whereas the older part of the cerebral cortex, i.e. the archicortex has three cellular layers.

It is the relative variations in regard to thickness or cell type, apart from several other criteria, that help in distinction between various neocortical architectonic fields. The layers, which are located in the upper part of the cortical grooves, also known as gyri seem to be much more clearly distinguished than in case of its deeper areas.

The cerebral cortex is interlinked with different subcortical structures like the basal ganglia and the thalamus. It is responsible for sending signals to them along outward connections, along with receiving impulses from them through the afferent connections. As it is, most sensory impulses are routed towards the cerebral cortex through the thalamus, while olfactory impulses pass through the olfactory bulb to the olfactory cortex. According to a rough estimate, as much as 99%, of the connections are from one area of the cortex to another, instead of the subcortical areas.

The various cortical layers contain a specialized distribution of neuron cell types, as well as connections with other cortical and subcortical regions. So, the cortical layering in the primary visual cortex can be detected with the naked eye in the fundus of the calcarine sulcus of the occipital lobe. As it is, the Stria of Gennari consists of axons, bringing visual information from the thalamus into the visual cortex.

Andersen-Tawil syndrome, or Andersen syndrome, as it is also known as, is a type of long QT syndrome. As it is, long QT syndrome or LQTS, as it is most commonly known as, refers to an unusual congenital heart condition, which is characterized by delayed re-polarization subsequent to depolarization of the heart, related to fainting as a result of ventricular arrhythmias that can get deteriorated into ventricular fibrillation. This might ultimately result in sudden death. As it is, Andersen-Tawil syndrome is a very rare genetic disorder.

People with Anderson-Tawil syndrome usually suffer from periods of muscle weakness, along with changes in the heart rhythm which is known as arrhythmia, along with developmental abnormalities. Now, the most usual changes, which affect the heart, are that of ventricular arrhythmia, that is a disruption affecting the rhythm of the lower chambers of the heart along with long QT syndrome. As explained before, Long QT syndrome denotes a heart condition that results in the heart muscle in taking longer than the usual time to recharge between the beats.

Symptoms of Andersen-Tawil syndrome might include widely spaced eyes, short stature, scoiosis, webbed toes/fingers, unusually short fingers, low set of ears, broad forehead, small jaw line, protruding jaws, as well as broad nasal root.

Andersen-Tawil syndrome is a disorder, which affects the heart and is characterized by a commotion in the rhythm lower chambers of the heart. This condition is referred to as ventricular arrhythmia. Along with this, other aspects related to long QT syndrome, might be present as well.

The condition is believed to be inherited as an autosomal dominant pattern. This means, that a single copy of the altered gene in each cell is enough for causing the disorder. In some of the cases, a patient with Andersen-Tawil syndrome receives the mutation from one of the affected parents, whereas, other cases are caused due to new mutations of the KCNJ2 gene. Such cases appear in people who have no history of this disorder, as far as their family is concerned.

As it is, the proteins prepared by the KCNJ2 gene makes a channel, which transports the potassium ions into the muscle cells. Now, the movement of these potassium ions through the channels is very important for the maintenance of the normal functions of the skeletal muscles that are of use for movement, as well as cardiac muscle. The mutations of the KCNJ2 gene, results in the alteration of the usual structure, as well as the functioning of the potassium channels.