Coughing up blood or hemoptysis is a serious sign because it frequently indicates a serious underlying lung disease. Because many of the lung disease heralded by this sign are treatable, systematic and through evaluation is required in order to discover hemoptysis etiology.

The first step when evaluating hemoptysis is to establish if it is really hemoptysis (blood from the bronchial tree or lungs) or from other sites, mimicking hemoptysis. In most cases, the patient's clinical history suggests that the expectorated blood is indeed being coughed up from the lungs or respiratory tract but in some cases there may occur difficulties in distinguishing whether the blood source is  the respiratory system or two other sites: bleeding in the sinuses, upper respiratory tract or in the nasopharynx, or blood which originates the gastrointestinal tract and was regurgitated. A patient medical history of frequent nosebleeds and hoarseness or other voice changes suggests bleeding from the upper respiratory tract. The presence of gastrointestinal symptoms usually suggests hematemesis. Moreover, an emesis (vomit) with a coffee ground aspect may be determined if the blood from a respiratory source has been swallowed.

The most common cause of hemoptysis is tuberculosis. The hemoptysis resulting from this disease is usually mild to moderate and is commonly associated with other signs and symptoms such as unexplained weight loss, purulent sputum (thick, yellowish- white discharge) and a history of exposure to Mycobacterium tuberculosis.

Bronchitis, the inflammation and swelling of the bronchi represents another common cause of hemoptysis. In this case. the blood originates from recurrent coughing which irritates and eventually breaks the respiratory mucosal lining. The hemoptysis in bronchitis is usually mild and is usually associated with a purulent sputum , low-grade fever and wheezing.

Bronchiectasis, the chronic dilation with a consequent infection of the bronchioles and bronchi determined by the bronchial obstruction is another cause of hemoptysis. The patients with bronchiectasis often present with a mild to moderate hemoptysys, a severe cough accompanied by a  chronic purulent sputum. Lung cancer and bronchogenic carcinoma are important causes of hemoptysis. In these cases, the bleeding is the result of the necrosis of the tumor ), the rupture of  some small blood vessels in the tumor area, of the tumor invading activity of one of the pulmonary blood vessels (in which case massive bleeding occurs).

In pneumonia ( lung infection determined by a vaste variety of microorganism) other symptoms beside hemoptysis are: a high fever, cough, and chest pain.Other less common causes of hemoptysis are: pulmonary infarction or embolism, pulmonary AVM, trauma, heart diseases, vascular disorders, drug use, anticoagulant medication, pulmonary endometriosis, aspergilosis, and autoimmune disorders.

Acid reflux disease, or more correctly, gastroesophageal reflux disease is the result of the failure of the body's normal antireflux mechanism to protect against the effortless movement of the gastric content from the stomach to the upper pars of the digestive tract (esophagus). Gastroesophageal reflux is a normal physiological process, with no signs, symptoms or consequent mucosal damage but in gastroesophageal reflux disease symptoms of heartburn and acid regurgitation occur.

The signs and symptoms of gastroesophageal reflux disease may be esophageal (heartburn , acid reflux, odynofagia) or extraesophageal.

The classical symptom for this disorder is heartburn.


The patients usually complain of a burning heeling rising from the stomach or epigastric area toward the neck and throat. This symptom usually manifests or exacebates postprandially, especially if the patient has eaten spicy foods, fats, chocolate or drank alcohol. Heartburn may also be exacerbated by bending over or recumbency, and , if it occurs at night it will interfere with sleeping. Inspite of the fact that this symptom is an important diagnostic clue, its intensity, frequency and duration is not a parameter in order to evaluate the severity and the degree of mucosal damage.

Another common symptom of gastroesophageal reflux disease is acid regurgitation. The postprandial effortless regurgitation of acid fluid, especially if exacerbated by recumbency is a very suggestive feature of gastroesophageal reflux disease. Most patients presenting with this symptom have a associated gastroparesis and a reduced LES (lower esophageal sphincter) pressure. In time, most of the patients will also develop esophagitis.

More than 40% of the patients complain of dysphagia which begins as a longstanding heartburn progressing slowly towards a dysphagia for solid foods. Still, most of them have a normal appetite and so weight loss occurs only rarely (in about 5% of the patients, most of them with severe esophagitis).

Waterbrash is a less common symptom of the disease and it consists in the spontaneous, sudden apparition of a salty or sour fluid which is caused by the salivary glands's  response to the disease.

Odynophagia or pain in swallowing may occur after the development of ulcerative esophagitis but it may be caused by a variety of other disorders, most of them with an infectious etiology. It is highly important that the underlying cause of odynophagia be sought.Other less common symptoms of gastroesophageal reflux disease are nausea,  hiccups, burping and vomiting.

The extraesophageal manifestations of the disease are: noncardial chest pain mimicking angina pectoris and which usually worsens after meals, chronic cough, asthma (there have been studies suggesting that gastroesophageal disease may have an impact on triggering and/or aggravating asthma),  posterior laringitis, vocal cord ulcers and granulomas, and dental erosion.

Peptic ulcers are lesions in the gastrointestinal lining, extending through the layer called muscularis mucosae. These lesions usually persist and are dependent on the acid-peptic characteristics of the gastric juice. The most important causes of this disease are the infection with Helicobacter pylori and the use of nonsteroidal antiinflamatory drugs (NSAID), including ibuprofen and aspirin but the patogenesis is multifactorial, the disease being favored by a variety of internal and environmental factors (gastric ph, hereditary factors, alcohol use, smoking, infectious agents and so on).

The classic ulcer symptom is acid dyspepsia, characterized as a burning epigastric pain with a strong tendency to occur when gastric juice is secreted in the absence of a food buffer (hunger pain), especially at night, Antisecretory drugs and food relief the pain, so many authors say that the patients "feed their ulcers".


The pain is localized in the epigastrium but it may also localize in the upper left quadrant or hypochondrium. the pain may also radiate to the back. Even after up to 3 years after the infection with Helybacter pilory has been eradicated, many patients complain of dyspepsia, probably related to sensitization of the nerve endings as a response to tissue injury.

Gastroesophageal reflux disease ) occurs in up to 60% of the patients with peptic ulcer disease. The disease is evident by esophagitis, heartburn and acid relux and there is well known that the obese patients are more predisposed to gastroesophageal reflux disease.

If the patient has not been using nosteroidal antiinflammatory drugs, the complications are mainly associated with a chronic peptic ulcer and mainly consist in the development of ulcer symptoms or in a change in the previous symptom pattern.
The most common complication of peptic ulcer is represented by penetrating ulcers. A penetrating ulcer usually presents with a more localized and intense pain (unlike in uncomplicated disease where the pain is perceived more as a vague visceral one). In pyloric outlet obstruction vomiting is a classical symptom and perforation is indicated by a diffuse, severe abdominal pain, with a sudden onset. Dizziness, melena (tarry, black stools), nausea and hematemesis (vomiting blood) may herald a hemorrhage.

Penetrating ulcers may also lead to fistulae. In the penetrating ulcers localized on the anterior gastric wall colonic fistulae may occur, and the patient presents halitosis (bad-smelling breath), feculent vomiting, dyspepsia, weight loss and postprandial diarrhea. A posterior perforation of an ulcer will have an insidious onset, with protean symptoms (which mainly consist in upper abdominal pain), caused by a localized retroperitoneal abscess or the contamination of by the peritoneal cavity. Hepatic penetration has also been documented.

Huntington's disease is an incurable, severe neurodegenerative genetic disorder affecting the cognitive activity and the motor coordination.  The disease is determined by a mutation with a dominant autosomal transmission. The age of the onset varies from early childhood to old age but the disease begins in most cases between the age of 35 to 45. When the disease's symptoms starts to develop before the age of 20 the disease is called juvenile Huntington's disease or the Westphal variant of Huntington disease.

The symptoms of Huntington's disease vary from patient to patient. Still, the disease's classical pattern consists in progressive motor, cognitive and emotional deterioration. In the initial stages the changes are subtle, and the cognitive and psychological symptoms may go unnoticed, the first symptom the patient observes being represented by chorea, a classical symptom which consists in involuntary, uncontrolled, jerky, fidgety movements of the face, body and limbs. The loss of muscle control also affects masticatory muscles and the diaphragm, affecting the patient's eating habits and so, choking may occur. Speech habits may also occur due to the improper functioning of the mouth and larynx muscles. The more obvious signs of motor impairment follow in time (after about 3 years after the first clinical manifestations of the disease) and consist in rigidity, postural instability, dysphagia (difficulty in swallowing), dysarthria (slurred speech), impaired control of eye movement and  poor control of the tongue, mouth muscles and diaphragm.

The constant movement increases the caloric necessities and this, combined with the problems with nutrition leads to weight loss, mineral and vitamin deficiency leading to a reduced anti infectious resistance, and a slower wound healing process.

The behavioral changes consist in moos swings, short term memory lapses, lack of concentration and  lack of interest in personal hygiene. Depression, a common psychiatric feature of Huntington's disease is not only determined by the disease but also by the impact it has on the patient's life. As the disease progresses, the patient will begin to exhibit other psychiatric symptoms such as delusions, paranoia, hallucinations,  (suggesting psychosis), compulsive behavior, addictive behaviors.

The cognitive decline in the patients with Huntington's chorea affects abstract thincking, judgement and memory. The patient has problems in understanding new information, in focusing attention, in problem solving, in planning and initiating activities, in initiating or maintaining conversations. There can also be observed a loss of initiative and organizational skills. Another commonly associated symptom is represented by sleep disturbances.

It should be mentioned that in juvenile Huntington disease the  seizures are also a very common feature. The difference between juvenile Huntington's disease and the typical form of the disease is that in the first one the disease has a very rapid course, with brief episodes of chorea and its main clinical feature is represents by rigidity.

Grave's disease is an autoimmune disorder which affects the thyroid gland, causing it to enlarge and increase its activity, determining symptoms of hyperthyroidism. The  disease is determined by the body's production of antibodies to the receptors fos TSH, the tireostimulating hormone. These antibodies bind to the receptors and stimulate it. As a result the folicular thyroid cells multiply, resulting an increased production of thyroid hormones(T3 and T4) and to hyperthyroidism.  The triggering factors of this abnormal immune reactions are : infection (viral and bacterial)  and severe stress. There have been studies trying to prove the genetic inheritance of Grave's disease but until now it has not been identified a gene responsible of triggering this disorder.

The signs and symptoms of Grave's disease are determined not only by the disease itself but also by the consequent hyperthyroidism. The most common features of the disease are: exophtalmos, pretibial myxedema, increased heart rate, fatigue, muscular weakness and symptoms related to hyperthyroidism.

Graves' ophtalmopathy or thyroid associated ophtalmopathy is the most typical finding in the patients suffering from this disorder. It determines the inflammation of the eyes and the tissues around them, including the orbital fat and the exterior muscles of the eyes and determining a  bulging aspect  of the eyes and optic nerve compression. In the early stages of Grave's ophtalmopathy the patient complains of eyelid retraction, irritation, photophobia. tearing and lagophtalmos (the incapacity of closing the eyes completely). As the disease progresses the symptoms become more marked and the extraocular muscles are affected (myopathy).

Due to the damage and fibrosis of the inferior rectus muscle, the patient will develop vertical diplopia, increased intraocular pressure and intermittent double vision. In the late stages of Grave's ophtalmopathy, exophtalmos occurs (leading to an impaired eye movement and optic neuropathy and optic nerve compression). The patient's visual acuity decreases, visual field defect, loss of color vision and afferent pupilary deffect occur. In this stage, any delay in treatment may lead to permanent blindness.

The goitre and the Graves' ophtalmopaty are the only symptoms directly determined by the disease. The other symptoms, caused by the increased levels of thyroid hormones are: hypertension, tachycardia, palpitations, fatigue, irritability, decreased concentration and diminished attention span. Dyspnea (shortness of breath), muscular weakness (especially in the muscles of the limbs), insomnia, and dry, brittle hair and nails are also common.

The disease may also have dermatological manifestations consisting in hypersensitivity reactions, erythema anulare centrifugum (a type of rash in which the central area clears as the eruption spreads). Acropachy, a condition similar to elephantiasis occurs rarely.

The hyperthyroidism has a marked impact on the patient's metabolism, leading to hyperglicemia, hypokalemia, weight gain and rhabdomylosis (muscle destruction determined by the increased energy consumption and by the depletion of the muscular deposits of glycogen).

The metabolic correlations established between the body's hormonal mechanisms will also affect the reproductive organs leading to amenorrhea or oligomenorrhea, infertility, difficulty conceiving and recurrent miscarriages. In men, gynecomastia may occur.

The polycystyc ovary syndrome is an endocrinological disease affecting almost 5% of women, most of them of fertile age. The disease is particularly defined not by the presence of cysts on the ovaries but by its clinical manifestations.


The signs and symptoms of this disorder are protean, and usually consist in weight gain or obesity, acne, amenorrhea, oligomenorrhea, infertility, oily skin, depression, hair loss and the deepening of the voice. These symptoms start manifesting usually in puberty but they may go unnoticed for years. An accurate history of regular menses (after the menarche) is important since it usually rules out the diagnosis of polycystic ovary syndrome.  The menstrual abnormalities are determined by the chronic anovulation, some women having secondary amenorrhea (absence of menses for 6 months) or oligomenorrhea (infrequent periods, nine or less in a year ). Because of the anovulation, the women with this condition may have difficulties in conceiving, polycystic ovary syndrome being the most common cause of women infertility. Another consequence of anovulatory menstrual cycles is represented by dysfunctional uterine bleeding.

The excess of androgen hormones may lead to another disturbing sign: hirsutism (increased hairgrowth with a typical male pattern , on the face-usually on the upper lip or under the chin-,  forearms, legs and abdomen. A severe form of acne  affecting the face, shoulders, chest and back and androgenic alopecia ( a male pattern baldness accompanied by the thinning of the hair) are also the consequences of the large amount of  androgen hormones. Another dermatological feature, acanthosis nigricans may occur, due to the reduced sensitivity to insulin. Acanthosis nigricans  usually presents as the thickening and the hyperpigmentation of the skin in the skin folds, underarms, around the neck and groin. Skin tags may also be found on the neck or in the axilair region.

Almost 50% of all women with polycystic ovary disease have weight problems by gaining weight easily and having difficulties in losing weight inspite of a balanced lifestyle. The adipous tissue is usually concentrated in the subumbilical area and around the waist. Weight problems increase the risks of developing other metabolic disorder.

The women with polycystic ovary syndrome have an increased risk of developing other important disorders. Hypertension, diabetes mellitus type 2, dyslipidemia, and cancer are the most important disorders to which these women are predisposed. Most women owith this syndrome experience in some degree a form of insulin resistance and almost 30% will have problems concerning the glucidic metabolism. The risk of developing diabetes mellitus increases in time. The hypertension, combined with high levels of LDL (bad cholesterol) and high levels of fats will increase the risk of cardiovascular disease.

The anovulation and the irregular periods will affect the lining of the uterus, increasing the risk for endometrial hyperplasia and, in time for endometrial carcinoma.

Wolfman syndrome is another term for hypertrichosis. Hypertrichosis is a dermatological condition which determines an excessive hair growth for a particular skin area (where hair does not usually grow). In some patients the disease may be congenital while in others the onset of the disease may be later, even in their adult lives.  Depending on the patient's age and hair growth pattern hypertrichosis may be classified. Depending on the surface of the body affected hypertrichosis may be generalized (it affects multiple sites or all the body) or localized (abnormal hair growth on a certain area or only a few sites, of a reduced surface). Depending on the age of onset, these two types may also be divided into congenital (the disorder was present at birth) or acquirea (which developed in time).


Generalized congenital hypertrichosis is a very rare condition of which fewer than 75 cases have been documented. This is a genetic disease determined by the addition or deletion of DNA fragments on chromosome 17. In this form of the disease the baby presents at birth the normal lanugo hairs ( long, light colored silky hairs which grow on all embryos in the womb ) but instead of falling in the first several months after birth, the hair remains on the baby's body, except the soles and the palms and the hair growth does not reduce in time. The hair density is increased on the face and shoulders.  In congenital hypertrichosis lanuginosa (a variant of the previously mentioned disorder) the hair is also lanugo type and the patients are usually normal or with mild dental malformations; but the disease's most disturbing aspect (the excessive hair growth) may reduce in time. Both this forms have in common gingival hyperplasia associated with dental malformations (fewer teeth, abnormal teeth eruption). The infants with these two diseases will aldo have a higher frequency of spina bifida.

Another form of congenital hypertrichosis lanuginosa is a hair growth pattern called Brachmann de Lange which is associated with mental retardation and growth delay. In this form of hypertrichosis the pilosity decreases in time.

Acquired generalized hypertrichosis is almost always a sign of an underlying or developing internal malignant process or it may be triggered by the exposure to chemical substances (in these circumstances the hair falls after the exposure ends). Acquired generalized hypertrichosis may also be caused by porphyries.

In localized congenital hypertrichosis the abnormal hairgrowth affects just one or a few sites, especially the back, ears and elbows (hypertrichosis cubiti). When affecting the back, hypertrichosis may suggest neural or spinal abnormalities. The infants with diabetic mothers will have excessive hair in the ear area.

Localized acquired hypertrichosis defines a category of transient hypertrichoses determined by a variety of causes such as trauma, sunburns, inflammation which transform the short, soft, non-pigmented hairs (vellus hairs) into coarse, pigmented terminal hairs as a response to the irritating factors. In this category are also included trichomegaly (excessive growth of the eyelashes) and Becker's nevus (excessive hair growth and pigmentation on the shoulders, determined by injuries and sunburns.)

The symptoms of pancreatic disease are usually protean so the blood tests have an important role in establishing the diagnosis. The diseases affecting the pancreas are: pancreatitis (acute, chronic, autoimmune and hereditary), pancreatic tumors, diabetes mellitus and pancreatic enzyme deficiency.


Acute pancreatitis is an inflammatory disease of the pancreas which may also affect peripancreatic tissue or remote organs. The disease is usually determined by gallstones, alcohol abuse, drugs or it may be idiopathic. Severe abdominal pain located in the epigastric region and sometime radiating to the back is almost always present and in some cases it is refractory to analgesics. The pain is in many cases more intense if the patient is supine. Muscular rigidity, an enlarged, palpable pancreas and abdominal tenderness may also be observed. The patient is frequently anxious or distressed, with a mild fever and hypotension. In severe necrotising pancreatitis hemoperitoneum may lead to a bluish discoloration around the umbillicus and tissue catabolism may be reflected by a blue-red discoloration on the flanks. Almost one in four patients who once had an attack of acute pancreatitis will experience, due to alcohol or cholelitiasis a recurrence.

In autoimmune pancreatitis the symptoms consist in mild abdominal pain, with diffuse swelling of the pancreas. The attacks of pancreatitis are rare. The disease is usually accompanied by obstructive jaundice.

In chronic pancreatitis the pain varies in intensity and it may be intermittent. The pain may be exacerbated after meals leading to anorexia and weight loss. Despite of the steatorrhea (fatty stools) most of the patients do not have the symptoms of vitamin deficiency. The maldigestion, another feature of chronic pancreatitis manifests as steatorrhea, fatigue, weight loss and chronic diarrhea. Mild fever and mild abdominal tenderness may also be observed.

Hereditary pancreatitis has similar symptoms to chronic pancreatitis. The clinical features of this disorder are:pancreatic calcification, steatorrhea, and recurring severe abdominal pain attacks. The patients with this disorder have an increased risk of pancreatic carcinoma.

Diabetes mellitus is a disorder in which the pancreas doesn't produce sufficient insulin. The disease has three forms: type one, type two or gestational. Polyuria (frequent urination) and polydipsia (increased thirst) are considered to be the classical symptoms of the disease. Inspite of the polyfagia (increased hunger) in type 1 diabetes a rapid significant weight loss may be observed. Vision changes (blurred vision) may occur, determined by the changes in the shape of the eye lenses. Kussmaul breathing is one of the first symptoms of the disease and it consists in the scent of acetone in the patient's breath. Abdominal pain, nausea, vomiting and altered mental state may also occur. In severe, diabetic ketoacidosis coma may occur, leading to death.

Pancreas enzyme insufficiency is determined by the inability of the pancreas to produce the necessary amount of digestive enzymes. This disorder is usually determined by the progressive pancreatic damage. The symptoms of this disorder are:weight loss, diarrhea and steatorrhea. Abdominal pain it is absent but in some cases it may be determined by other disorders affecting the pancreas.

The clinical features of pancreatic endocrine tumors are usually determined by the increased amount of hormones and only in the late stages the tumor itself will cause abdominal pain. Sometimes, weight loss, bleeding, fatigue and jaundice may occur.

Celiac disease (or coeliac disease) is a genetically predisposed autoimmune disease which affects the small intestine. This disease is determined gliadin, a protein found in wheat, barley and rye. The immune system cross-reacts with the intestinal tissue, after the tissue transglutaminase modifies the gliadin, and so, an inflammatory is triggered.This process leads to damage of the villi found on the intestinal mucous membrane, damage known as villous atrophy. This disturbs the absorbtion of nutrients. Inspite of the fact that this disease is the result of the action of a wheat protein, this disease should not be mistaken with the wheat allergy.


The signs and symptoms of the disease are determined by the intestinal damage and by the consequences of the malabsorbtion. The most usual symptoms of celiac disease are: diarrhea, vomiting, weight loss, fatigue, and abdominal distension, but even though this disease is primarily an intestinal disorder, bowel symptoms may be subtle or absent. In some cases the diagnosis may be rather based on symptoms determined by the malabsorbtion . For example in subtle disease, the adults may only complain of fatigue and their blood tests show a mild anemia and the children may have psychologiacal problems and malabsorbtion-related disturbances.

T he diarrhea is a very characteristic sign of celiac disease  and it usually manifests as the presence of voluminous, discolored and malodorous stools. The cramping, bloatedness accompanied by abdominal distension (determined by the gas resulted from fermentation processes) abdominal pain and lesions on the mucous membrane lining the inner side of the cheeck are other common features of celiac disease. As the disease progresses and the intestine is more affected, lactose intolerance may occur. The gastrointestinal symptoms may be various and some patients may have a normal intestinal tranzit or even display a tendency towards constipation.

Celiac disease may lead to other intestinal disorders such as stricturing or ulcerative jejunitis or it may increase th risk of developing adenocarcinoma and lymphoma.

As a consequence of the impaired intestinal absorbtion other disturbances may also occur determined by the deficit in vitamins, calcium, and nutrients. Weight loss may occur in adults due to the insufficient amount of aminoacids, glucose and fats absorbed and in children stunted growth and pubertal delay are determined by this form of malnutrition. The malabsorbtion of calcium may lead to osteopenia, osteomalacia and osteoporosis, affecting the bone metabolism and increasing the risk of fractures. Anemia may be determined by more than one cause, all related to the impaired absorbtion function: by the malabsorbtion of iron there will occur iron deficiency anemia and the malabsorbtion of vitamin B12 and folic acid will lead to megaloblastic anemia.

At the moment the only effective treatment consists in a gluten-free diet. Nevertheless there are people with refractory disease whose condition does not improve after taking the dietary measures. In these cases the treatment with corticosteroids should be considered.

Down's syndrome is a chromosomial disorder caused by the existence of an extra 21 chromosome. Down's syndrome affects the cognitive abilities and development, facial appearance and physical growth.

The symptoms of Down's syndrome are usually noticed at birth but the syndrome may be identified during pregnancy by a medical procedure named amniocentesis.

The most common facial features of Down syndrome are: a flat face, a flat nasal bridge, small nose, the specific upward slant to the eyes, epicantus (the presence of a skin fold in the medial corner of the eye), small ears that usually fold at the top, abnormally small mouth (microstomia) and chin (microgenia),  Brush field spots (white spots in the iris) large protuding tongue and microcephaly (abnormally small head).

The babies with this disorder are usually born earlier than normally, they  have smaller feet and hands, their articular ligaments are loose and they have a reduced muscular tone (hypotonia). Hypotonia a main feature in Down's syndrome. The muscles of the patient feel floppy and it usually affects all the skeletal muscles in the body. Therapy for hypotonia should be started rapidly, in order to reduce the disease's impact on the development of motor skills.


An early intervention is also the key in preventing the impact of the low muscular tone on the future speaking and eating skills of the baby. Microstomia (the small mouth), accompanied by the undeveloped sinuses and the frequent respiratory infections the individuals with Down's syndrome are exposed to may lead to respiratory problems, thus leading to the baby's necessity to breathe through mouth and so, as consequence there will be encouraged the protuding tongue. This symptom, combined with hypotonia will lead to nurshing problems, since the child will not be able to eat properly and later on, there will occur problems with eating solid food.

Other features of Down's syndrome are: the Simian crease (unique palmar crease- in babies without the disease there are two palmar creases on each hand), short limbs, the lack of the distal phalanx in the little finger,flat, broad hands with short fingers, weaker or absent Monro reflexes, broad flat feet with short toes and with an abnormally large space between the big toe and the second.

The individuals with this disorder usually have a lower than average IQ and cognitive abilities. They usually have a speech delay not only because of the intellectual impairment but also determined by hearing loss, malformations of the acustic conduct or middle ear problems.

Vision problems will also occur in more than 70% of children with this syndrome. The ophtalmological problems may range from myopia and hypermetropia to blocked tear duct cataracts and astigmatism.

The congenital heart defects that occur with this disorder are atrioventricular septal defect, ventricular septal defect and atrial septal defect, requiring surgery. Endocrine problems may also occur, the most frequent are represented by thyroid disorders (hypothyroidism and hyperthyroidism) but pituitary problems may occur as well thus leading to a shortage of growth hormone, which leads to an even more marked growth delay.

The gastrointestinal tract is frequently affected by many anatomical and functional abnormalities. Aganglionnic megacolon, duodenal atresia, anular pancreas, tracheo-esophageal fistula and malabsorbtion disorders are the most common gasrtointestinal problems.