Syndrome in Clinical Medicine
P.K.Ghatak,MD
In a NIH publication in 2003, Dr. Franz Calvo et al, defined syndrome as a recognizable complex of symptoms and physical findings for which a direct cause is not necessarily understood. Once the medical science identifies a causative agent or process with a high degree of certainty, physicians may then refer the process as a disease and not a syndrome.
Some well known syndromes now are called diseases and to illustrate - an example is Cushing's disease and Cushing's syndrome. In 1912 Dr. Cushing reported a new disease he call polyglandular syndrome due to malfunction of the Anterior Pituitary gland, He published this entity in 1932 as basophil adenomas of the Pituitary body and named it Pituitary basophilism. Symptoms of the disease - gained excessive weight, mostly around the back of the neck, face and abdomen. Also developed high blood pressure, diabetes, acne and facial hair. In subsequent years the condition was known as Cushing's syndrome. Further studies identified the cause was a tumor of anterior pituitary producing an excess amount of ACTH hormone which in turns putting out excess corticosteroids from the Suprarenal glands. Similar changes were also detected when patients took steroid for a prolong time, as one of the anti-rejection drug following kidney transplants. And also seen in certain cancer of lungs secreting excess amount of polypeptide having similar hormone like actions of the suprarenal gland. Now Cushing's Disease term is reserved for symptom complex arising from tumor of the anterior pituitary and Cushing's syndrome is applied all others causes which can produce some features of Cushing's disease.
If one looks up Syndrome in the Wikipedia, will be surprised to find more than 1600 syndromes. In the index of any textbook of medicine where every entry is listed in alphabetical order, one finds only 3 entries under syndrome, the rest of the syndromes are under the first letter of a name attached to the person discovered the illness. Not all the listed syndromes, however, follows this rule. Some names are retained because the name refers to well understood symptoms by the public, like - Milk - Alkali syndrome and Irritable Bowel Syndrome.
Recent rapid advances in genetics, MRI imaging , sonography, immunology and biochemist solved many obscure causes of syndrome. In the lifetime experience of any well rounded physician might have not see more than 30 syndromes. Certain specialties like Pediatrics are likely see more syndromes.
A few syndrome will be presented here to give a chance to the readers to get an idea about syndrome.
Down syndrome.
Down syndrome arises from abnormalities of chromosome 21. It occurs in 75% cases as inherited and 25% as spontaneous. Each cell of the body contain an additional one full or partial copy of chromosome 21. This generally happen as non-jurisdiction or translocation between chromosome 21 and 14 or 21 and 21 or 21and 22. In 2 to 3 % cases it also occur due to Mosaicism.
Some of the common features of Down syndromes are mental retardation, flat cranium and flat nose bridge, a short neck, large tongue compared with the floor of the mouth, prominent epicanthal fold, structural heart defects, truncal obesity, poor muscle tone an delayed mile stones of development.
Polycystic Ovary Syndrome.
Originally the Polycystic Ovary syndrome was called Stein-Leventhal syndrome because this pair of investigators were the first to report it in 1935. In 1990 NIH added two additional criteria - multifactorial genetic errors and insulin resistance, and finally in 2003 ultsonographic detection of more than 20 cysts in ovary was added and named it Polycystic ovary syndrome. The cause of this syndrome is unknown and symptoms vary widely.
A typical case have these features: Symptoms of irregular and scant menstrual flow or delayed monarchic. Development of acne and facial and body hair of masculine type, obesity, hypertension and insulin resistance and diabetes mellitus. Most cases are due to excessive androgen activities but androgen is normal in minority of cases. In few cases the polycystic ovary syndrome is detected during investigation of failure to conceive. If not treated properly there is high likelihood of development endometrial carcinoma later in life.
Klinefelters syndrome. This congenital condition affects only male child due to having an extra X chromosome. The condition is also known as 47 XXX. The genetic abnormality occur randomly either in the development of ovum or sperm. The condition is generally detected at puberty when the child failed to develop muscle mass and develop feminine body type - gynecomastica, no facial hair and wide hips. They have small genitalia and testicle, scant or absent sperm production and have long legs and short torso. Many have learning difficulties and lags behind reading and writing skill.
Not all affected have all the above features and may pass as normal and only correctly diagnosed much later when one fails to father children. They carry risk of breast and extragonadal germ cell cancers and also osteoporosis.
Turner's syndrome. Turners syndrome is also known as 46 XO. This congenital condition is seen only in female offspring, arises due to missing a whole or part of sex chromosome X; but whether that missing X chromosome is paternal or maternal is not known. The gene responsible for bone growth is SHOX gene and it is missing in Turners syndrome results in the abnormalities of bones in Turners syndrome. At birth the child may appear normal except for a web neck and a broad chest. As the child reaches age 9 or 10 the growth slows down, develop no secondary sexual characters and menstrual cycles. Other features are cubits vulgus, aortic/ pulmonary stenosis and high BP, diabetes mellitus, hypothyroidism and osteoporosis.
Fragil X syndrome: It is a X link cause of mental retardation. Males are more severely affected than females. Incidence is 1:4000 male birth and 1:10,000 in females. Symptoms in female are learning difficulties, variable degrees mental retardation and early onset of menopause. In male the physical characteristics are large ears, prominent jaw bone, high pitched voice, Mitral valve prolapse and increased immobility of joints. This syndrome is associated with autism.
The tip of the long arm of chromosome X carry the mutated Fragil RNA gene results from undue expansion of CCG repeats. More repeats are present more mental retardation is detected.
Marfan syndrome. Marfan syndrome is an autosomal dominant inherited disorder of the connective tissue due to mutations in the Fibrillin gene (FBNA1) on chromosome 15. This results in aberrant TGFB1 and TGFB2 activities. Clinical features of Marfan syndrome are tall structure, long arms and legs, scoliosis, pigeon chest wall deformity(Pectus excavatum), dislocated eye lenses, mitral valve prolapse, aortic root dilatation, aortic incompetence and aortic aneurysm and dissection.
Ehlers-Danlos syndrome. This is another connective tissue autosomal dominant inherited disorder. Mutation of many genes, last count 20 genes, are implicated, and based on severity of symptoms 11 varieties are known. Those who have severe symptoms have mutation of COL5A1 and COL5A2 genes, other mutated genes are TNXB, ADMTS2, PLOD1, FKBP14 and many others. Mutations result is formation of collage tissue in a haphazard fashion and functionally of poor quality specially of the skin, skeletal muscles, arteries, bones and internal organs. Major symptoms include fragile velvety skin, which peals off easily and forms extensive scars. Aneurysm of artery and dissection and rupture of aneurysm and other changes of eyes, heart and bones mentioned under Marfan syndrome.
Irritable bowel syndrome. Irritable bowel syndrome fits the classical definition of the syndrome. A group of symptoms originate in colon and small intestine but cause remains known. Common symptoms are - a sense of not able to evacuate completely after a bowel movement, constipation and low grade abdominal cramps, flatulence and diarrhea, often hard and lumpy stool and diarrhea on the same day, and several bowel movements a day. Various theory are put forward including stress, pressure of modern life, precooked meals, food additive, change of colon bacterial colonies and low tolerance to pain. Both sexes are affected and age of onset - from teens to elderly. It is a common illness.
Milk-Alkali syndrome. It is a self made syndrome due to taking an excessive amount of Calcium supplement to prevent osteoporosis and condition is accelerated and made worse taking mega dose vitamin D3. In previous generation people suffered this complication from taking excessive amount of Tums, Maalox and Mylanta for heart burns and peptic ulcer diseases. Excess alkali present in the form of carbonate in these compounds shifts the blood pH towards the alkaline side. High blood calcium results in excess amount of calcium excreted in the urine. Kidney stones and urinary bladder stones may develop. Renal colic, chronic pain around loin and back are usual symptoms of kidney stone. Left untreated, patients may end in renal failure.
Abdominal Compartment syndrome. This is a serious and often fatal condition arises from several causes but often seen in severe burn victims. Other causes are organ transplants, prolonged abdominal surgery specially repair of abdominal aorta rupture, bullet or knife penetrating injury with severe intra abdominal hemorrhage. Sepsis, abdominal abscess, severe peritonitis and others. Fluids and inflammatory exudates accumulate in and around organs and raises intra abdominal pressure over 20 cm of Hg. This impairs arterial supply and block venous and lymph drainage, producing further damages abdominal organs. Immediate proper fluid management and abdominal surgery in needed to relive the high intra abdominal pressure.
Sudden Infant Death Syndrome (SIDS). A healthy newborn child suddenly stops breathing and dies during sleep. In majority of cases are due to suffocation due to putting children face down in a soft bed for sleep; which favors obstruction of mouth and nose. About 20 % cause remains unknown.
Thoracic outlet syndrome.
Just below the clavicle at a point it turns towards the shoulder Subclavian artery and subclavian veins and all the nerves arise from the brachial plexus enter the chest wall and course down the medial side of the arm. There is just enough room for the structure to pass. In an abnormal situation like fracture of the clavicle and hematoma formation, a cervical rib and osteoma of the first rib that space becomes too tight for these structures and pressure on artery produce pain in the arm and hand, pressure on the vein swelling of hand and forearm and bluish discoloration of fingers, Pain over the nerve produces tingling numbness of fingers and muscle weakness. The pressure must be relived by surgery to prevent permanent damages to the hand.
Tarsal tunnel syndrome. Just like carpal tunnel syndrome,Tarsal tunnel syndrome may develop at the ankle joint. Symptoms and causes are practically same except for the site.
Inappropriate ADH secretion. Blood volume and serum osmolarity are maintained by feedback loops on the control center located in the hypothalamus and posterior pituitary gland. In lower blood volume and high sodium content of blood (high osmolarity) no Anti Diuretic Hormone (ADH) should be released from the posterior pituitary. But if ADH is still released in such condition, the situation is called Inappropriate ADH secretion. The causes are many, only important few will be mentioned here.
Syndrome X. Syndrome X is due to abnormal microcirculation of the coronary arteries or coronary vasospasm which results in Angina pectoris.
Syndrome of apparent mineralocorticoid excess, This syndrome is due to 11 beta hydroxysteroid dehydrogenase deficiency inherited on a autosomal recessive mode. Symptoms are early onset of hypertension in childhood, low serum potassium and metabolic alkalosis.
Metabolic syndrome. Metabolic syndrome is a more recent entry in syndrome category; previously the components of this symptoms were known as essential hypertension, hypercholesterolemia, obesity and diabetes mellitus. Under the new name those previous entities are refined and redefined, instead of hypercholesterolemia it is now low HDL cholesterol and high triglyceride. Obesity is now abdominal obesity, Diabetes is replaced by above impaired fasting blood glucose. People Metabolic syndrome are in high risk of developing coronary arterial disease, diabetes mellitus and cerebrovascular accidents.
Stokes - Adam syndrome. This syndrome is a well established a century ago, when physicians used their well cultivated skill of observation and taking pulse over several minutes. Main features of Stokes - Adam syndrome is sudden loss of consciousness and fall to the ground and having epileptic seizures due to complete heart block ( third degree in new definition) and pulse rate of 35 or below. Ventricular fibrillation and ventricular tachycardia also unconsciousness and seizures. At one time it was called Cardiac seizure and that name was better known than Stokes-Adam syndrome.
Long Q-T syndrome. This is an electrocardiogram finding. The time interval between the beginning of q wave and end of T wave on the tracing of an ECG (EKG) is normally 0. 43 millisecond when the heart rate in 72/ minute. In slower heart rate Q-T interval increases in a predictable way. In several cardiac diseases and quinine, procainamid, digitalis, over the counter cold medicines and many other medications can cause undue prolongation of Q-T interval. More longer the interval is there is more chance of Ventricular ectopic beats and precipitation of ventricular tachycardia and ventricular fibrillation. A particular form of multifocal and multi directional ectopic ventricular beats called Torsades des pointes (a French word, meaning twisting around points) is a forerunner of Ventricular fibrillation and death.
Torsades des pointes
Sick sinus syndrome. This is another very significant ECG finding. The natural cardiac pacemaker is the sinus node. In oxygen deprivation from any reason, electrolyte imbalance and certain medications, sinus node fails to generate the electrical pulse wave for heart muscle to contract. This can manifest as slow heart rate over 3 seconds, 1st, 2nd and 3rd degree heart block. These changes are variable and in some cases variable cardic block can be intermittent. The detect the condition a special cardiac monitor is used, which can trace every cardiac beats and record on a preset program. This allows closer examination of any abnormal heart beat and suitable treatment can be offered – often a pacemaker. Main symptom of sick sinus syndrome is missing a heart beat, irregular pulse, palpitation, fluttering sensation in chest, confusion and loss of balance and fall.
Goodpasture syndrome. Goodpasture syndrome is an example how antibody, generated to fight an unidentifiable infection, mistakes its own kidneys as foreign and attacks the collagen tissue present in the the basement membrane of glomeruli and walls of alvioli of lungs, results in hemorrhage in the kidney and lungs. Main symptoms are bloody urine and coughing out of blood. Other significant symptoms are shortness of breath, chest pain, fatigue , anemia, high BP, fatigue , nausea and vomiting. It is a major illness and requires immediate medical attention.
Alport syndrome. Alport syndrome is multisystem inherited disorder involving collagen IV tissue and results in renal failure, deafness and visual impairment. The defective gene is carried on X chromosome. Male child develops glomerulonephritis at early age and progresses rapidly and unless treated dies by age 40, females are less frequently affected and disease progress slowly.
Nephrotic syndrome. Nephrotic syndrome is a stage in renal failure arises from protein loosing glomerulonephritis. Presence of large amount of proteinin the urine amkes urine foamy, hypoalbumia produces puffy eyes, pale puffy face, ankle edema and scrotal edema. With the further progression of disease ascites and plural effusion are seen. Anemia, fatigue, weight gain from accumulated water develop. Intercurrent infection is common.
Carcinoid syndrome. In a previous blog, carcinoid syndrome was discussed in details. See foot note.
Carcinoid syndrome is due production of a number polypeptides which have hormone like effects released from one variety of neuroendocrine tumor. Carcinoid tumors are generally arise in the small intestine, stomach, colon, appendix , rectum and liver and pancreas, and also arises in the bronchial tree of the lung. Carcinoid secrete serotonin, histamine, kallikrein, tachykinins and prostaglandin. These are potent vasodilators and produce intense vasodilatation, hypotension, watery diarrhea, asthma like bronchospasm and intense flushing of the face and body. The tumors are small and can be benign or malignant, but pathologically can not be determined whether a tumor is benign or maliganat. In malignant variety the tumor metastasize in the liver.
Dumping syndrome. Dumping syndrome is a number of gastrointestinal symptoms occur when a few minutes after a meal. Vagotomy and reducing stomach capacity by surgery are the principal causes of Dumping syndrome. Following any such stomach surgery, the food leaves the stomach prematurely and enters the duodenum in large amounts overstretching the duodenal wall causing upper abdominal crampy pain, sense of abdominal fullness, nausea, diarrhea, weakness and lightheadedness. And later develops palpitation and rapid heart beats.
Short bowel syndrome. Certain medical illnesses require taking out a part of the small intestine. The small intestine becomes shorter. This changes absorptive capacity of the small intestine and patients develop loss of weight and nutritional deficiency. Crohn disease and ischemic bowel are most common causes.
Zollinger-Ellsion syndrome ( Z-E Syndrome). Z-E syndrome is due to Gastrin producing tumor - Gastrinoma of the duodenum or pancreas. Gastrin stimulates gastric acid production. Majority of Z-E syndrome are spontaneous in origin but 25 % are due to Multiple endocrine neoplasm of type 1( MENS1). Several complication generally develop and are pretty serious – gastric perforation and profuse Gastric bleeding, esophagitis and esophageal atresia.
Budd Chiari syndrome. This syndrome is due to hepatic vein thrombosis which produces liver enlargement, upper abdominal pain, hepatic necrosis followed by cetrilobular fibrosis and jaundice and liver failure. Patients may develop this condition due to hypercoagulable state from inherited conditions like Factor V Leiden, Protein C and S deficiency or from acquired conditions like myeloproliferative disorders or Paroxysmal Nocturnal Hemoglobinuria.
Sjorgen syndrome. This syndrome is named after a Swedish physicians Dr Henrik Sjorgen who reported cases of chronic arthritis associated with dry eyes and dry mouth. It is an autoimmune disease producing chronic lymphocytic inflammation of salivary and lacrymal glands. The microvascular and ductal blockage results from inflammation produce dryness. In addition, exocrine glands of the skin, GI tract, joints, lungs, CNS and kidneys are involved. Arthritis of the hand resemble rheumatoid arthritis. ANA blood test is positive over 1:256 dilution and in addition SS-A, SS-B and RP serology are positive. Sjorgen patients run risk of B-cell lymphoma (non-Hodgkin lymphoma)and antiphospholipid antibody production results in vascular thrombosis.
Gullian Barry syndrome. This is an example of Autoimmune nervous system disease. Antibodies attack myelin sheath of the peripheral nerve and damaged sheath eventually damages the core nerve fibers of axons. Peripheral neuritis causes weakness of muscles of limbs, muscles of respiration and face. What triggers antibody production is not known but a viral infection is likely. From the onset of symptoms of muscle weakness and tingling numbness and pain, the disabilities reaches maximum in 3 weeks and respiratory failure develops.
Pickiwian syndrome. Nearly 200 years ago, Author Charles Dickens in his famous publication “The posthumous papers of the Pickwick club” described obese individual awake but hypoventilate due to reduced sensitivity to hypercapnia of the respiratory center and frequently dowsed off. Pickiwian syndrome is chosen to honor Dickens's astute observation of human nature. People with this syndrome have BMI over 30Kg/square M. Fat accumulates around neck, chest and upper abdomen, have blunt respiration drive even in presence of the strongest stimulus- respiratory acidosis and hypercapnia. Laptin insensitivity explaining the reason for obesity.
Premenstrual syndrome. Million of women suffers irritability, mood changes, weight gain and puffiness of face and hands and feet before the menstrual flow begins. These symptoms are due to hormonal changes necessary to induce shedding of extra growth of endometrium which developed in anticipation of fertilization of a ovum and the beginning of pregnancy.
Congenital Myesthenia syndrome. This syndrome is inherited by autosomal recessive pattern, and also rarely by autosomal dominant mode. Weakness of muscles of the eyelids, eye muscles that moves the eyes, muscles of chewing and swallowing are commonly affected. Repeated movements make weakness worse. Mutation of CHRN gene is responsible for over 50 % of cases, the rest of the cases are due to mutation of RAPSN, CHT, COLQ DBC7 genes. Children fails to suck breast milk. Swallowing and any normal physical activities are affected. Severity of disabilities varies depending upon the mutated genes. All these genes are responsible to provide codes of protein synthesis required for normal functioning of transmission of nerve signal across the neuromuscular junction.
Eaton-Lambert syndrome. Eaton-Lambert syndrome is an autoimmune disease. Immune system produces antibodies which mistakenly attack the Calcium Channels on the nerve endings. This results in fewer functional pathways for nerves to deliver signals to the effector sites involving both somatic and autonomic nervous system. In construst with Myesthenic syndrome, repeated action improves muscle functioning. Small cell carcinoma of the lung is the most commonly responsible for this syndrome, other malignancy also can produce this syndrome. The leg muscles are commonly affected, the effects of autonomic nervous system can be severe in cardiovascular system and urogenital system.
Wernicki - Korsakoff syndrome. This syndrome is a combination of Wernicki encephalopathy and Korsakoff psychosis. Chronic alcohol abuse is the underlying cause of Vitamin B1 deficiency which the cause of this syndrome however, other nutritional deficiency are associated. The symptoms are - inability to develop memory of current events, confabulation and talkativeness, lethargy, confusion and coma. MRI shows atrophy of the thalamus, hippocampus, hypothalamus and enlarged ventricles. The symptoms are reversible if treatment can be started before Wernicki encephalopathy sets in.
Ramsey Hunt syndrome. This is a special case of Shingles. The one side of the face develop palsy of lower motor neuron type and is associated with vesicular rashes on external auditory canal, pinna, mucous membrane of the oropharynx . This is due to reactivation of Vericella - zoster virus (chicken pox virus). The symptoms are pain in the ear, deafness, tinnitus, vertigo, balance and ambulatory difficulties.
Loefflers syndrome. Loefflers syndrome is due to very high eosinophil count in the blood associated with infiltrate of eosinophils in the lung tissue producing pneumonia like symptoms and bronchospasm. In early days it was due to ascaris lumbricoides parasitic infestation when ascaris larvae wondered around to find its fianl residing place in the small intestine. The alergic reaction generated an eosinophilic immune reaction. Now other parasites are known to produce similar reactions during their tissue migration.
Waterhouse- Federick syndrome. Waterhouse-Federick syndrome is a real emergency situation during a miningococcacal meningitis with bilateral adrenal hemorrhage due to toxemia. It produces acute adrenal insufficiency manifested as shock, hypotension, vascular collapse and cerebral, renal and pulmonary inefficiencies. Many other bacterial and viral infection are also known can also produce this syndrome. Immediate intervention to normalize blood volume and tissue oxygenation must be instituted and intravenous corticosteroids admistration is administered along with antibiotics and other therapeutic agents.
Gilbert syndrome. This is an inherited benign liver condition involving high blood unconjugated bilirubin level causing jaundice. Other parameter of liver functions are all normal and no treatment is required.
Osler-Weber- Rendu syndrome. This is also known as Heriditory Hemorrhagic Telangectasia. This inherited in an autosomal dominant mode. It is due to presence of multiple gene mutations. Arteriovenous malformation is present on skin, mainly on the face and mucous membrane of nose, mouth , stomach, GI tract, liver, lungs, spinal cord and brain. Bleeding from involved organs can produce a wide varieties of symptoms, bleeding in the brain can be fatal.
Footnote: For further reading see https://humihealth.blogspot.com/Medical matters.
1. Carcinoid syndrome, - Carcinoid and Neuroendocrine tumors. Blog. Medical matters dated 13 june 2011. 2. Loefflers syndrome. - Round worm Ascaris lumbricoides.Dec 6.2023 3. Korsakoff psychosis. - Speech disorder. Oct,16,202. 4. Sjorgen syndrome. - Collagen & mixed connective Tissue diseases.Dcc14,2022. 5.Zollinger- Ellison synfrome. - Perptic ulcers.Feb 16, 2023 .6.Polycystic Ovary syndrome.Insulin resistanceMarch10,2022. 7. Cushings synrome. Pituitary gland. August 20,2021. + Adrenal gland Oct22,2021. 8.Rumsey Hunt syndrome. Chicken pox Feb16,2023, 9.Myesthenic syndrome.Neuromusculat transmission, Dec22,2022. 10. Milk- Alkali syndrome. Kidney stones April16,2022.
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