Russell-Silver syndrome

Background

Growth is characterized by increases in height and weight as well as bodily changes that occur as a person develops. Other aspects of growth include the growth of hair and bones and the transition of baby teeth to adult teeth.
Human growth can be tracked through various stages beginning with conception and continuing as the fetus develops. Once born, a healthy human will progress from a newborn/infant (zero months to one year), to a toddler (1-4 years), child (5-12 years), adolescent (13-19 years), young adult (20-35 years), adult (35-40), middle-aged adult (40-59), and finally to an elderly adult or senior citizen (60+ years).
Biological development or growth begins when a child is conceived. Conception happens when sperm from a man fertilizes an egg in a female resulting in a human embryo which develops and grows for nine month's in the mother's womb.
According to the U.S. Centers for Disease Control and Prevention (CDC), childhood is a time of rapid growth and cognitive, social, and emotional development that is accompanied by changes in organ system functioning, metabolic capabilities, physical size, and behavior.
Human growth may be affected by heredity, gender, illness and medications, nutrition, hormones, and psychosocial environment, among other factors. A warning sign of a growth abnormality is below or above average height and/or weight. During the first year of life, an infant should grow an average of 7-10 inches. During the second year, a toddler will grow approximately five inches. During the third year, toddlers grow three inches on average. From age four years until puberty, growth should be at least two inches/year. During puberty, girls may grow 2.5-4.5 inches/year. Puberty occurs later in boys and is usually characterized by a growth of 3-5 inches/year. After puberty, there is little to no additional growth of bones.
Growth problems may be genetic or acquired. Genetic growth abnormalities can be generally categorized as overgrowth disorders or undergrowth disorders. Overgrowth syndromes can be diagnosed by unusually large size at birth, excessive postnatal growth, and increased weight, increased length, and/or increased head circumference. There is an increased risk of cancer in a number of the overgrowth syndromes.
Common overgrowth syndromes include Bannayan-Riley-Ruvalcaba syndrome, fragile X syndrome, gigantism, hemihyperplasia, Maffucci syndrome, neurofibromatosis, Proteus syndrome, and Weaver syndrome. A common cause of overgrowth syndromes is the overproduction of growth hormone by the pituitary gland before adolescence and a distinctive pattern of overgrowth called acromegaly.
Undergrowth syndromes may be caused by musculoskeletal and metabolic diseases, including those that cause alterations in the skeleton. Examples of undergrowth syndromes include dwarfism, Ellis Van Creveld syndrome, and Russell Silver syndrome.
Human growth disorders may affect growth symmetrically or may act regionally affecting the normal proportionality of the human body. Growth disorders may occur in infants, kids, or teens and may prevent them from meeting expectations of growth, such as failure to gain height and weight in young children to short stature or delayed sexual development in teens. Diseases of the kidneys, heart, gastrointestinal tract, lungs, bones, or other body systems may affect growth.

Signs and symptoms

Acromegaly: Symptoms of acromegaly include: abnormal growth of the hands and feet, swelling of the hands and feet, protrusion of the brow and lower jaw, enlargement of the nasal bone, and abnormal teeth spacing. Overgrowth of bone and cartilage often leads to arthritis. When tissue thickens, it may trap nerves, causing carpal tunnel syndrome, which results in numbness and weakness of the hands. Body organs, including the heart, may enlarge. Other symptoms of acromegaly include joint aches, thick, coarse, oily skin, skin tags, enlarged lips, nose, and tongue, deepening of the voice due to enlarged sinuses and vocal cords, sleep apnea, breaks in breathing during sleep due to obstruction of the airway, excessive sweating and skin odor, fatigue and weakness, headaches, impaired vision, abnormalities of the menstrual cycle and sometimes breast discharge in women, erectile dysfunction in men, and decreased libido.
Dwarfism: Signs and symptoms of dwarfism include short stature (an adult height of four feet 10 inches or under), a shortened trunk with longer limbs, an average-sized trunk but small arms and legs, a relatively long trunk and shortened upper parts of their arms and legs, a large head with a prominent forehead, a flattened bridge of the nose, shortened hands and fingers, and reduced muscle tone.
Ellis-van Creveld syndrome: Sign and symptoms of Ellis-van Creveld syndrome include: stillbirth (common); death in early infancy (common); dwarfism; short arms and legs, especially the forearm and lower leg; sparse, absent, or fine textured hair; cleft lip or palate; tooth abnormalities (peg teeth, widely spaced teeth, teeth present at birth (natal teeth), delayed teeth, or absent tooth formation); nail problems, including absent or deformed nails; limited range of motion; extra fingers (polydactyly); epispadias or an undescended testicle (cryptorchidism); and heart defects such as a hole in the heart (atrial septal defect).
Fragile x syndrome: Symptoms of fragile X are often milder in girls than in boys. Common signs of fragile X include: intellectual disabilities that range from mild learning disabilities to more severe mental retardation; long ears, faces, and jaws; loose, flexible joints; flat feet; ability to extend joints like the thumb, knee, and elbow further than normal; behavior challenges; a feeling of being afraid or anxious in new situations; trouble paying attention; overly-aggressive behavior; overly shy disposition; trouble speaking clearly; presence of a stutter; trouble understanding the speaker's tone of voice or that person's body language; irritation with bright light, loud noises, or the way something feels; a dislike of being touched; and difficulty making eye contact with other people.
Gigantism: Symptoms of gigantism include: excessive growth during childhood, frontal bossing and a prominent jaw, thickening of the facial features, disproportionately large hands and feet with thick fingers and toes, increased perspiration, weakness, secretion of breast milk, irregular menstruation, headache, delayed onset of puberty, and double vision or difficulty with peripheral vision.
Growth hormone deficiency (GHD): GHD is characterized by a slowed or absent increase in height; slow growth before age five; short stature (below fifth percentile on a standardized growth chart, or an adult less than five feet tall); absent or delayed sexual development in an adolescent; headaches; excessive thirst with excessive urination; and increased urine volume.
Neurofibromatosis: Neurofibromatosis (NF) is characterized by the presence of multiple neurofibromas (tumors). Caf?-au-lait spots, which are the most common sign of NF, are the flat, pigmented spots on the skin, which are named for the French term for coffee (caf?) with milk (lait) because of their light tan color. In darker-skinned people, caf?-au-lait spots appear darker in color than surrounding skin. Iris nevi, or Lisch nodules, are clumps of pigment in the colored part of the eye (iris) that usually appear around puberty.
Panhypopituitarism: Symptoms of panhypopituitarism include fatigue, weakness, sensitivity to cold, decreased appetite, weight loss, abdominal pain, low blood pressure, headache, visual disturbances, short stature (less than five feet) if onset is during a growth period, and loss of armpit or pubic hair. Symptoms distinct to women include cessation of menstrual periods, infertility, lack of sex drive, and failure to lactate. Male symptoms may include decreased sexual interest and loss of body or facial hair. Common symptoms in children include slowed growth and sexual development. Symptoms vary depending upon the severity of the disorder, the number of deficient hormones, and their target organs. Additional symptoms that may be associated with this disease include weight gain (unintentional), joint stiffness, hoarseness or changing voice, hair loss, and facial swelling.
Russell Silver syndrome: Symptoms of Russell Silver syndrome include low birth weight, poor growth, short height, delayed bone age, normal width of head, wide forehead with a small triangle-shaped face and small, narrow chin, arms and legs of differing lengths, curving of the pinky toward the ring finger, short, stubby fingers and toes, cafe-au-lait (flat, pigmented spots on the skin that are named for the French term for coffee (caf?) with milk (lait) because of their light tan color) spots, arm span less than height (short arms), kidney problems, gastroesophageal reflux disease, swelling of the esophagus (food pipe), and failure to thrive.
Sotos syndrome: Symptoms of Sotos syndrome include: a long, narrow face; a high forehead; flushed (reddened) cheeks; a small, pointed chin; down-slanting palpebral fissures; intellectual impairment; behavioral problems; attention deficit hyperactivity disorder (ADHD), phobias; obsessions and compulsions; tantrums; impulsive behaviors; problems with sound production; stuttering; a monotone voice; weak muscle tone (hypotonia); an abnormal side-to-side curvature of the spine (scoliosis); seizures; heart or kidney defects; hearing loss; and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.

Diagnosis

Acromegaly: Blood and imaging tests may be used to diagnose acromegaly. The growth hormone (GH) level in a person's blood can be tested to determine if it is elevated. However, fluctuations in GH levels make such testing less reliable. More accurate information is obtained when GH is measured under conditions that normally suppress GH secretion. The oral glucose tolerance test is often used to diagnose acromegaly in healthy people. IGF-I levels may also be measured; IGF-I levels are much more stable than GH levels over the course of the day making them a more practical and reliable screening measure. After acromegaly has been diagnosed with blood tests, a magnetic resonance imaging (MRI) scan of the pituitary can locate and detect the size of the tumor causing GH overproduction. Computerized tomography (CT) scans may also be used.
Dwarfism: Some types of dwarfism can be identified through prenatal testing. However, most cases are not identified until after the child is born. A diagnosis is based on the child's appearance, failure to grow, and X-rays of the bones.
Ellis-van Creveld syndrome: Skeletal X-rays, echocardiograms, urinalysis, chest X-rays, ultrasounds, and genetic testing may be available for diagnosis.
Fragile x syndrome: There is a Fragile X DNA test has that can be accompanied by genetic counseling. It has been available since 1991, provides accurate diagnosis of fragile X syndrome and extremely accurate carrier detection, and is reliable for people of any age (it can also be performed prenatally). The fragile X cytogenetic test is also available. Although fragile X syndrome is the most common cause of inherited intellectual impairment, it is underdiagnosed due to wide variability in the clinical presentation of the disorder. Although certain physical and behavioral features are often associated with fragile X syndrome, they are not always present. In at least 10% of cases in males, intellectual impairment is the only presenting sign. The classic triad of long face, prominent ears and macroorchidism is present in just 60% of cases. Mental retardation is not a constant, either. Approximately 15% of males with fragile X syndrome have an IQ above 70 (Hagerman et al., 1994). In cases such as these, the possibility of fragile X syndrome may not be considered. Similarly, females with fragile X syndrome may not be correctly diagnosed because symptoms may be subtle.
Gigantism: Blood tests that detect an increase in insulin growth factor-I (IGF-I) levels are used to diagnose gigantism. Imaging scans, such as MRI (magnetic resonance imaging) and CT (computerized tomography) scans, can detect pituitary tumors.
Growth hormone deficiency (GHD): A physical examination including weight, height, and body proportions will show signs of slowed growth rate and deviation from normal growth curves. Tests may include the following: hand X-rays, DEXA (Dual Energy X-ray Absorptiometry), measurement of growth hormone and associated binding protein levels (IGF-I and IGFBP-3), tests that measure other hormone levels (lack of growth hormone may not be an isolated problem), X-rays of the head, and MRIs of the head.
Neurofibromatosis: Tentative diagnostic criteria include: a family history of NF1, six or more light brown ("cafe-au-lait") spots on the skin, presence of pea-sized bumps (neurofibromas) on the skin, larger areas on the skin that look swollen (plexiform neurofibromas), freckling under the arms or in the groin area, pigmented bumps on the eye's iris (Lisch nodules), skeletal abnormalities such as tibial dysplasia (bowing of the legs) or thinning of the shin bone, and tumors on the optic nerve that may interfere with vision. Laboratory tests are now available in most cases to determine whether a person has NF 1 and 2. Gene linkage testing is available for families with NF1 and NF2. Direct gene testing is currently available for NF1 and may be available in the near future for NF2. These tests may be used for presymptomatic diagnosis.
Panhypopituitarism: Diagnosis of hypopituitarism must confirm low hormone levels due to an abnormality of the pituitary gland. The diagnosis must also rule out disease of the organ affected by this hormone. Diagnostic methods include: cranial CT (computerized tomography) scans; cranial MRIs (magnetic resonance imaging); and tests for serum luteinizing hormone (LH), serum follicle stimulating hormone (FSH), serum testosterone level, serum estradiol (estrogen), serum cortisol, serum ACTH, T4 (thyroid hormone), serum thyroid stimulating hormone (TSH), serum thyroid stimulating hormone response to thyroid-releasing hormone, serum growth hormone (GH), and serum insulin-like growth factor 1 (IGF-1) levels. In some cases, one of the hormones produced by the pituitary may be elevated in the blood stream if a patient has a pituitary tumor which is producing an excessive amount of that hormone. The tumor itself may be pressing against the rest of the cells of the pituitary, leading to low levels of other hormones.
Russell Silver syndrome: A physical exam is performed to detect the following symptoms of Russell-Silver syndrome: a triangle-shaped face with broad forehead, a small, pointed chin, and a thin, wide mouth. While specific laboratory tests for the diagnosis of Russell-Silver syndrome are not available, the following tests may be helpful: blood sugar, growth hormone, skeletal survey to rule out other conditions that may mimic Russell-Silver syndrome, chromosome testing, and bone age testing.
Sotos syndrome: Doctors may use the following signs of Sotos syndrome for diagnosis: a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). Other symptoms may include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.

Integrative therapies

Strong scientific evidence:
Arginine: Arginine is considered a semi-essential amino acid because although it is normally synthesized in sufficient amounts by the body, supplementation is sometimes required (for example, due to inborn errors of urea synthesis, protein malnutrition, excess ammonia production, excessive lysine intake, burns, infection, peritoneal dialysis, rapid growth, or sepsis). Symptoms of arginine deficiency include poor wound healing, hair loss, skin rash, constipation, and fatty liver.
Intravenously administered arginine can be used to evaluate levels of growth hormone in individuals with suspected growth hormone deficiency. This procedure is called the growth hormone reserve test. This test may be beneficial, for example, in patients with suspected pan-hypopituitarism, growth or stature abnormalities, gigantism or acromegaly, or pituitary adenoma. The U.S. Food and Drug Administration (FDA) has approved this indication for arginine; however, it should only be performed under the direction of a licensed doctor.
Arginine has been well tolerated by most people in studies lasting for up to six months, although there is a possibility of side effects in some individuals. Stomach discomfort, including nausea, stomach cramps, or an increased number of stools, may occur. People with asthma may experience a worsening of symptoms if arginine is inhaled, which may be related to allergy. Headache has also been reported.
Good scientific evidence:
Probiotics: Probiotics are beneficial bacteria (sometimes referred to as "friendly germs") that help to maintain the health of the intestinal tract and aid in digestion. They also help keep potentially harmful organisms in the intestines (harmful bacteria and yeasts) under control. Most probiotics come from food sources, especially cultured milk products. Probiotics can be consumed as capsules, tablets, beverages, powders, yogurts, and other foods. There is evidence that young children (ages 6-36 months) who receive infant formula with Bifidobacteria Bb12 supplementation may achieve faster growth than those who receive formula without the supplementation. Balanced intestinal health aids in the absorption of nutrients.
Probiotics are generally considered safe and well-tolerated. Use cautiously in patients prone to infections or those with compromised immune systems, such as those with HIV/AIDS, or in infants born prematurely or those with immune deficiency. Use cautiously in patients with gastrointestinal disorders or in those sensitive or intolerant to dairy products containing probiotics or to lactose. Avoid with known allergy or sensitivity to probiotics. Probiotics may cause diarrhea in sensitive individuals.
Unclear or conflicting scientific evidence:
Calcium: Calcium is the most abundant mineral in the human body and has several important functions. More than 99% of total body calcium is stored in the bones and teeth, where it supports the structure. The remaining 1% is found throughout the body in blood, muscle tissue, and intracellular fluid. Calcium is needed for muscle contraction, blood vessel constriction and relaxation, the secretion of hormones and enzymes, and nervous system signaling. A constant level of calcium is maintained in body fluid and tissues so that these vital body processes function efficiently. Calcium helps support proper bone growth and maintenance.
Growth of very low birth weight infants correlates with calcium intake and retention in the body. It is possible that human milk fortifiers commonly used may have inadequate levels of calcium for infants of very low birth weight. Bone mineralization is also lower in very low birth weight infants at theoretical term than infants born at term. Use of a formula containing higher levels of calcium has been suggested to allow improved bone mineralization in these infants.
Avoid if allergic or hypersensitive to calcium or lactose. High doses taken by mouth may cause kidney stones. Avoid with hypercalcaemia (high levels of calcium in the blood), hypercalciuria (high levels of calcium in urine), hyperparathyroidism (high levels of parathyroid hormone), bone tumors, digitalis toxicity, ventricular fibrillation (ventricles of the heart contract in unsynchronized rhythm), kidney stones, kidney disease, or sarcoidosis (inflammation of lymph nodes and various other tissues). Calcium supplements made from dolomite, oyster shells, or bone meal may contain unacceptable levels of lead. Use cautiously with achlorhydria (absence of hydrochloric acid in gastric juices) or arrhythmia (irregular heartbeat). Calcium appears to be safe in pregnant or breastfeeding women; however, it is suggested to consult with a healthcare provider to determine appropriate dosing during pregnancy and breastfeeding.
Copper: Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains, and fruits as well as shellfish, avocado, and beef (organs such as liver). Because copper is found in the earth's crust, most of the world's surface water and ground water used for drinking purposes contains small amounts of copper. Severe copper deficiency may retard growth. Adequate intake of micronutrients including copper and other vitamins may promote growth as measured by length gains. Copper deficiency may occur in infants fed only cow-milk formulas (which are relatively low in copper content) or synthetic low lactose diets, premature/low-birth weight infants, infants with prolonged diarrhea or malnutrition, malabsorption syndromes (including celiac disease, sprue, or short bowel syndrome), cystic fibrosis, or during intravenous total parenteral nutrition (TPN) or other restrictive diets.
Copper toxicity is rare in the general population. Excess copper consumption may lead to liver, kidney, or nerve damage.
Polydextrose: Prebiotics are nutrients fermented in the large bowel that favor the growth of desirable large bowel microflora (healthy bacteria). Polydextrose, a carbohydrate with low digestibility, has been shown to have prebiotic activity. More high-quality studies with polydextrose supplementation are needed in order to determine its usefulness as a prebiotic in infant formulas for childhood growth promotion.
Use cautiously in patients with gastrointestinal problems, diarrhea, pancreatic problems, kidney disease, skin conditions, diabetes, or in those using antidiabetic agents or lipid lowering medications. Avoid use in patients with an allergy or hypersensitivity to polydextrose.
Qi gong: Children are capable of receiving instruction in internal Qi gong as a health promotion activity and it may have some behavioral benefits. However, it is unclear whether Qi gong can promote physical growth in children. More research is needed.
Qi gong is generally considered to be safe when learned from a qualified instructor and practiced in moderation. In cases of potentially serious medical conditions, Qi gong should not be used in place of more proven therapies. Caution is advised in patients with diabetes, hypoglycemia, bleeding disorders, low blood pressure, or in patients taking agents for these disorders. Caution is advised in immune-compromised individuals, pregnant or breastfeeding women, in patients with pre existing psychoses, or in vulnerable individuals without a psychiatric history.
Fair negative scientific evidence:
Zinc: Some limited evidence suggests that supplementation with zinc plus iron (but not zinc alone) may improve linear growth (length) of stunted infants with low hemoglobin. Overall, studies using zinc alone do not suggest any effect on growth.
Zinc is generally considered safe when taken at the recommended dosages. Use amounts regularly exceeding the recommended upper tolerance levels (greater than 40 milligrams daily) under a physician's guidance only. Use cautiously in patients with bleeding disorders, diabetes, or low blood sugar levels, or in patients taking agents for these conditions. Use cautiously in patients with high cholesterol or blood fats, a high risk of developing heart disease, skin disorders, gastrointestinal disorders, liver disease, genitourinary conditions, blood disorders, nerve disorders, lung or respiratory disorders, immune disorders, or kidney disease, or in patients taking antidepressants, potassium-sparing diuretics, antibiotics (particularly tetracyclines and quinolones), iron, penicillamine, thyroid hormones, or copper. Avoid in patients who are homozygous for hemochromatosis (a metabolic disorder involving the deposition of iron-containing pigments in the tissues and characterized by bronzing of the skin, diabetes, and weakness) or with a known allergy or hypersensitivity to zinc compounds. Avoid use of intranasal Zicam?.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

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Types of the disease

General: The endocrine system helps control growth and development throughout the body. It consists of small organs that regulate body functions through the release of hormones.
The pituitary gland is a small, oval-shaped organ at the base of the brain that releases a variety of hormones into the blood stream, including growth hormone (GH). Growth hormone is a protein hormone that stimulates growth and cell reproduction in humans and other animals. Once in the blood, GH travels to bone, muscle, and other tissues where it has many effects. The hypothalamus, a small structure located at the base of the brain just above the pituitary gland, controls the release of growth hormone by the pituitary gland. The principal stimulator of growth hormone secretion is called growth hormone-releasing hormone (GHRH).
In children, GH stimulates linear growth (height) and contributes to the development of muscle and bone and the distribution of fat throughout the body. In adults, GH affects energy, muscle strength, bone health, and psychological well-being. Having either too much or too little GH can cause health problems, such as acromegaly, which is excessive growth. Excess GH in adults is most common in middle-aged men and women.
Acromegaly: Acromegaly is a hormonal disorder that occurs when the pituitary gland in the brain, which makes GH, produces excessive amounts of GH. The excess GH may come from benign, or noncancerous, tumors on the pituitary called adenomas. Symptoms of acromegaly may appear at any age although it is most often diagnosed in middle-aged adults. Acromegaly is treatable in most patients; however, because of its slow onset, it often is not diagnosed early or correctly and may lead to serious illness and premature death. According to the National Endocrine and Metabolic Diseases Information Service, the most serious health consequences of acromegaly are type 2 diabetes, high blood pressure, increased risk of cardiovascular disease, and arthritis. Patients with acromegaly may also have an increased risk for colon polyps, which can develop into colon cancer. According to The Hormone Foundation, approximately 60 out of every one million Americans have acromegaly.
Dwarfism: Dwarfism is generally defined as an abnormally short stature, usually an adult height of four feet, 10 inches or less. Adult height among people with dwarfism ranges from two feet eight inches to four feet eight inches. More than 200 different conditions can cause dwarfism. Achondroplasia, a genetic condition that causes the arms and legs to be short in comparison to the head and trunk, causes about 70% of all dwarfism. Other genetic conditions, kidney disease, and problems with metabolism or hormones can also cause short stature. Achondroplasia occurs most often in families where both parents are of average height; 85% of children with achondroplasia are born to average-size parents.
Ellis-van Creveld syndrome: Ellis-van Creveld syndrome, or chondroectodermal dysplasia, is a rare genetic disorder associated with short-limb dwarfism, polydactyly (additional fingers or toes), malformation of the bones of the wrist, dystrophy of the fingernails, partial hare-lip, cardiac malformation, and often prenatal eruption of the teeth.
Fragile x syndrome: Fragile X syndrome is the most common form of inherited mental retardation. A problem with a specific gene, called the Fragile X Mental Retardation 1 (FMR1) gene, causes the disease. Normally, the gene makes a protein needed for brain development. The mutation causes a person to make little or none of the protein, which results in the symptoms of fragile X. People with only a small change in the gene might not show any signs of fragile X; people with bigger changes may have severe symptoms. Common traits of fragile X syndrome include: intelligence problems, ranging from learning disabilities to severe mental retardation; social and emotional problems, such as aggression in boys or shyness in girls; and speech and language problems, especially in boys.
Gigantism: Gigantism is the result of an excessive secretion of growth hormone during childhood before the closure of the bone growth plates; it is characterized by the overgrowth of long bones and a very tall stature. The excess GH secretion is frequently caused by a benign (noncancerous) pituitary gland tumor. Underlying medical conditions, such as multiple endocrine neoplasia type 1 (MEN-1), McCune-Albright syndrome (MAS), neurofibromatosis, or Carney complex, may also cause gigantism. Gigantism is inherited and occurs in fewer than 100 children in the United States.
Growth hormone deficiency (GHD): Growth hormone deficiency (GHD) is the condition of having too little growth hormone (GH) characterized by abnormally short stature with normal body proportions. Growth hormone deficiency can be categorized as either congenital (present at birth) or acquired. In the United States, it is estimated that about 20,000 children and 35,000 adults have GHD.
Neurofibromatosis: Neurofibromatosis is a genetic disorder of the nervous system that affects how nerve cells form and grow, usually causing tumors to grow on nerves. Neurofibromatosis may be inherited or it can happen because of a genetic mutation. There are three types of neurofibromatosis: type 1 (NF1) causes skin changes and deformed bones and usually starts at birth; type 2 (NF2) causes hearing loss, ringing in the ears, and poor balance and often starts in the teen years; and schwannomatosis, which causes intense pain and is the rarest type.
Panhypopituitarism (hypopituitarism): Hypopituitarism is a rare condition caused by low levels of pituitary hormones. The pituitary gland is a small bean-shaped gland located at the base of the brain that secretes hormones that influence nearly every part of the body. In hypopituitarism, there is a short supply of one or more of these pituitary hormones. This deficiency may affect growth, blood pressure, and reproduction.
Russell Silver syndrome: Russell-Silver syndrome, which presents at birth, results in poor growth, low birth weight, short height, and differences in the size of the two sides of the body. Other symptoms include: delayed bone age, wide forehead with a small triangle-shaped face, small, narrow chin, arms and legs of differing lengths, curving of the pinky toward the ring finger, short, stubby fingers and toes, "cafe-au-lait" (flat, pigmented spots on the skin that are named for the French term for coffee (caf?) with milk (lait) because of their light tan color) spots, arm span less than height (short arms), kidney problems (hydronephrosis, renal tubular acidosis, posterior urethral valves, horseshoe kidney), gastroesophageal reflux disease, swelling of the esophagus (food pipe), and failure to thrive. An estimated 7-10% of patients with this syndrome have a defect in a gene called the maternal uniparental disomy (UPD) for chromosome 7. In the other 90-93% percent of patients, a cause cannot be identified; most cases occur in a person whose family has no history of the disease. Males and females are equally affected.
Sotos syndrome: Sotos syndrome, also called cerebral gigantism, is a rare genetic disorder that is associated with excessive physical growth during the first 2-3 years of life and may be accompanied by mild mental retardation, delayed motor, cognitive, and social development, low muscle tone, and speech impairments. Children with Sotos syndrome are typically large at birth and are often taller, heavier, and have larger heads than is normal for their age. Most cases of Sotos syndrome occur sporadically. However, familial cases have also been reported.

Causes and risk factors

Acromegaly: Acromegaly is caused by extended overproduction of growth hormone (GH) by the pituitary gland. The pituitary gland produces several important hormones that control body functions such as growth and development, reproduction, and metabolism.
In over 95 percent of acromegaly patients, a benign tumor of the pituitary gland, called an adenoma, produces excess GH. Pituitary tumors are labeled either micro- or macro-adenomas, depending on their size. Most GH-secreting tumors are macro-adenomas, which are larger than one centimeter. These larger tumors may compress surrounding brain structures depending on where they are located. For example, if the tumor grows to the side, it may enter an area of the brain called the cavernous sinus potentially damaging the nerves located there. If the surrounding normal pituitary tissue is compressed, the production of other hormones may be altered. These hormonal shifts can lead to changes in menstruation and breast discharge in women and erectile dysfunction in men. If the tumor affects the part of the pituitary that controls the thyroid, another hormone-producing gland, then thyroid hormones may decrease. Weight gain, fatigue, and hair and skin changes may result from too little thyroid hormone. If the tumor affects the part of the pituitary that controls the adrenal gland, the hormone cortisol may decrease. Weight loss, dizziness, fatigue, low blood pressure, and nausea often result from too little cortisol. Some GH-secreting tumors may also secrete too much of other pituitary hormones. In rare cases, adenomas may produce thyroid-stimulating hormone. Experts recommend that a qualified healthcare professional examine all pituitary hormones in acromegaly patients as rates of GH production and the aggressiveness of the tumor vary greatly. Some adenomas grow slowly and symptoms of GH excess are often not noticed for many years. Other adenomas grow more rapidly and invade surrounding brain areas or the venous sinuses, which are located near the pituitary gland. Younger patients tend to have more aggressive tumors. Most pituitary tumors develop spontaneously and are not genetically inherited. They are the result of a genetic mutation (not present at birth) in a single pituitary cell, which leads to increased cell division and tumor formation.
Rarely, acromegaly is caused by tumors of the pancreas, lungs, and other parts of the brain. These tumors also lead to excess GH, either because they produce GH themselves or, more frequently, because they produce GHRH, the hormone that stimulates the pituitary to make GH. Nonpituitary tumors can be surgically removed causing GH levels to fall thus improving the symptoms of acromegaly. In patients with GHRH-producing nonpituitary tumors, the pituitary may still be enlarged and may be mistaken for a tumor. It is recommended that a qualified health professional carefully analyze all pituitary tumors removed from patients with acromegaly in case a tumor elsewhere in the body is causing the disorder.
Dwarfism: Dwarfism may be caused by any one of more than 200 conditions, most of which are genetic. Achondroplasia is the most common type, accounting for 70% of all cases of short stature. Dwarfism is typically caused by a spontaneous genetic mutation in the egg or sperm cells prior to conception. In more rare cases, the condition is caused by genes inherited from one or both parents. Two average-sized parents can have a child with short stature (though this is far more likely to occur with a spontaneous mutation). Similarly, depending on the type of condition causing the short stature, it is possible for little people to have an average-size child. What prompts a gene to mutate is not yet clearly understood. The change is seemingly random and unpreventable and can occur in any pregnancy. Generally, when average-size parents have a child with short stature due to a spontaneous mutation, it is rare to have a second child who is also of short stature. However, if parents have some form of dwarfism themselves, the odds are much greater that their children will have it as well. A genetic counselor can help determine the likelihood of passing on the condition in these cases. Dwarfism has other causes, including metabolic or hormonal disorders in infancy or childhood. Chromosomal abnormalities, pituitary gland disorders (which influence growth and metabolism), absorptive problems (when the body can't absorb nutrients adequately), and kidney disease can all lead to short stature.
Ellis-van Creveld: Ellis-van Creveld, inherited as an autosomal recessive trait, results from defects in one of two Ellis van Creveld syndrome genes:EVC and EVC2. The two genes lie next to each other on chromosome 4. It is unclear how this unusual arrangement affects the presentation of the syndrome. The severity of the disease varies from person to person. The highest rate of the condition is seen among the Old Order Amish population of Lancaster County, Pennsylvania.
Fragile x syndrome: Fragile X syndrome is caused by a change, or mutation, in a single gene called the Fragile X Mental Retardation 1 (FMR1) gene. This gene normally makes a protein the body needs for the brain to develop. However, when there is a change in this gene, the body makes only a little bit or none of the protein, which can cause the symptoms of fragile X. Fragile X is inherited, which means it is passed down from parents to children. Also, parents can have children with fragile X even if the parents do not have fragile X themselves. The changes in the gene can become more serious when passed from parent to child. Some people may only have a small change in their FMR1 gene (called a premutation) and may not show any signs of fragile X. Other people may have bigger changes in the gene, called a full mutation.
Gigantism: Gigantism is caused by an excessive secretion of growth hormone during childhood, before the closure of the bone growth plates. This excess growth hormone causes overgrowth of the long bones and very tall stature.
Growth hormone deficiency (GHD): GHD can be caused by a variety of genetic mutations (such as in the Pit-1 gene, Prop-1 gene, growth hormone receptor gene, and the growth hormone gene), absence of the pituitary gland, or severe brain injury. However, in most cases, no underlying cause of the deficiency is found. Growth retardation may become evident in infancy and persist throughout childhood. The child's "growth curve," which is usually plotted on a standardized growth chart by the pediatrician, may range from flat (no growth) to very shallow (minimal growth). Normal puberty may or may not occur, depending on the degree to which the pituitary can produce adequate hormone levels other than growth hormone. Growth hormone deficiency may be associated with deficiencies of other hormones, including: thyrotropins (control production of thyroid hormones); vasopressin (controls water balance in the body); gonadotropins (control production of male and female sex hormones); and ACTH or adrenocorticotrophic hormone (controls the adrenal gland and its production of cortisol, DHEA, and other hormones). Physical defects of the face and skull can also be associated with abnormalities of the pituitary or pituitary function. A small percentage of infants with cleft lip and cleft palate have decreased growth hormone levels.
Neurofibromatosis: Neurofibromatosis (NF) is an extremely variable disorder. NF may be extremely mild with multiple "caf?-au-lait" (flat, pigmented spots on the skin that are named for the French term for coffee (caf?) with milk (lait) because of their light tan color) spots and a few dermal neurofibromas. More severe cases may result in one or more serious complications. The majority of people with NF (an estimated 60%) have mild forms of the disorder. Another 20% have correctable problems and 20% have serious and persistent problems. Many of the serious problems in NF, such as congenital defects of the bone, scoliosis, optic glioma, and neurological impairment leading to learning disability or mental retardation, may be evident at birth or may develop prior to adolescence. People with NF who have reached adulthood without having these problems are unlikely to develop them.
Panhypopituitarism: In hypopituitarism, there is an absence of one or more pituitary hormones, which leads to loss of function in the gland or organ that it controls. The hormones secreted by the pituitary gland (and their functions) are: growth hormone (GH), which stimulates growth of tissues and bone; thyroid stimulating hormone (TSH), which stimulates the thyroid gland to secrete hormones that affect the body's metabolism; adrenocorticotropic hormone (ACTH), which stimulates the adrenal gland to secrete cortisol; cortisol, which helps to maintain blood pressure and blood sugar; prolactin, which stimulates female breast development and milk production; luteinizing hormone (LH), which controls sexual function in males and females; follicle stimulating hormone (FSH), which controls sexual function in males and females; antidiuretic hormone (ADH), which controls water loss by the kidneys; and oxytocin, which stimulates contraction of the uterus during labor and milk release from the breasts. Causes of hypopituitarism may be: tumors of the pituitary gland or hypothalamus, head trauma, brain tumor, radiation, brain surgery, stroke, subarachnoid hemorrhage (from a burst aneurysm), or infections of the brain and the tissues that support the brain. Occasionally, hypopituitarism may be caused by uncommon immune system or metabolic diseases, such as sarcoidosis, histiocytosis X, and hemochromatosis. Hypopituitarism can also be part of a rare complication following pregnancy, a condition called Sheehan's syndrome.
Russell Silver syndrome: In 7-10% of patients with this syndrome, there is a defect in a gene called the maternal uniparental disomy (UPD) for chromosome 7. However, the cause of this genetic defect has not been identified for most patients. Most cases of this syndrome occur in an individual whose family has no history of the disease. The features associated with Russell-Silver syndrome have been linked to many other genetic problems such as: chromosome rearrangements, autosomal dominant and recessive families (rarely reported), and abnormal methylation of chromosome 11p15. The estimated number of people who develop this condition varies greatly. Some estimates suggest it affects about one in 3,000. Other reports suggest it affects one in 100,000 people. Males and females are equally affected.
Sotos syndrome: Mutations in the NSD1 gene, which provides instructions for making a protein that is involved in normal growth and development, cause Sotos syndrome. About 95 percent of Sotos syndrome cases occur in people with no history of the disorder in their family. A few families have been described with more than one affected family member. Sotos syndrome has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Sotos syndrome is reported to occur in one in 10,000 to 14,000 newborns. Many cases of this disorder remain undiagnosed however, so the true incidence may be closer to one in 5,000.

Prevention and self-management

There are several things an individual can do to help ensure that a child grows and develops normally. These include proper rest, proper nutrition, and adequate exercise. Growth disorders that are inherited may still be manageable with the help of doctors and therapists.
Adequate exercise: Because obesity is a growing problem in children, parents should ensure that children exercise regularly, in combination with receiving proper nutrition. Bicycling, hiking, in-line skating, sports, or other enjoyable physical activities can motivate a child to stay active and can help promote good health and fitness habits to help the child maintain a healthy weight.
Height measurement: Measuring height can ensure that a child is growing at a normal rate. The best height measurement is done by having the child stand in bare feet against a wall without a baseboard with knees straight, and hips and shoulders touching the wall. The head should be facing straight ahead. Children under two years may be measured lying on their backs on a flat surface with a measuring device that has adjustable ends. It is normal to see a decrease in height when switching from lying to standing measurements (approximately one-half to one inch).
Proper nutrition: A balanced diet, including limiting refined carbohydrates (such as sugars and white breads), eating less saturated fats, and eating plenty of fresh vegetables will help a child reach his or her full growth potential.
Rest: Sleep patterns vary by age and individual child, but most kids need an average of 10 - 12 hours of sleep per night. Sleep gives growing bodies the rest they need to continue growing properly. Sleep also helps regulate the release of growth hormone.

Related terms

Achondroplasia, acromegaly, adrenal, cerebral gigantism, childhood growth promotion, chondroectodermal dysplasia, congenital, cortisol, Creutzfeldt-Jacob disease, Down's syndrome, dwarfism, Ellis-van Creveld syndrome, fragile X syndrome, endocrinologist, GH, GHD, GHRH, gigantism, growth, growth hormone, growth hormone deficiency, growth hormone reserve test, growth hormone stimulation, growth hormone-releasing hormone, hormone, hypopituitarism, hypothalamus, IGF-1, insulin-like growth factor-1, mad cow disease, neurofibromatosis, panhypopituitarism, pituitary disorder diagnosis, pituitary gland, Russell Silver syndrome, sleep apnea, thyroxine, Sotos syndrome, Turner's syndrome.

Treatment and complications

Acromegaly: Current treatment options for acromegaly usually include surgery to remove the tumor, radiation of the pituitary gland, or prescription medications including somatostatin analogues (SSAs), growth hormone receptor antagonists (GHRAs), or dopamine agonists. A possible complication of surgery is damage to the surrounding normal pituitary tissue, which requires lifelong use of pituitary hormone replacement. The part of the pituitary that stores antidiuretic hormone important in water balance may be temporarily or, rarely, permanently damaged and the patient may require medical therapy. Other potential problems include cerebrospinal fluid leaks and, rarely, meningitis, a bacterial or viral infection of the meninges, the outer covering of the brain.
Dwarfism: Treatments for dwarfism focus on alleviating symptoms and complications. Current treatment options include hormone therapy and surgery for correcting bone problems or for limb lengthening. Complications of dwarfism-related disorders can vary greatly, but some complications are common among a number of conditions. Women with disproportionate dwarfism may develop respiratory problems during pregnancy. A caesarean delivery is almost always necessary because the size and shape of the pelvis doesn't allow for vaginal delivery. People of average height often hold misconceptions about people with dwarfism. Children with dwarfism are particularly vulnerable to teasing and ridicule.
The characteristic features of the skull, spine, and limbs shared by most forms of disproportionate dwarfism result in some common problems. These may include: delays in motor skill development, such as sitting up, crawling, and walking; frequent ear infections (otitis media) and risk of hearing loss; bowing of the legs (genu varum); difficulty breathing during sleep (sleep apnea); pressure on the spinal cord at the base of the skull; crowded teeth; progressive severe hunching (kyphoscoliosis) or swaying (lordosis) of the back; in adulthood, narrowing of the channel in the lower spine (lumbosacral spinal stenosis), resulting in pressure on the spinal cord and subsequent pain or numbness in the legs; arthritis in adulthood; weight gain that can further complicate problems with joints and the spine and place pressure on nerves.
With disorders causing proportionate dwarfism, problems in overall growth often result in complications with other poorly developed organs. For example, kidney or heart problems often present in Turner syndrome can have a significant effect on a child's general health. An absence of sexual maturation associated with growth hormone deficiency or Turner syndrome affects not only physical development but also social functioning.
Ellis-van Creveld syndrome: There is currently no known single treatment for Ellis-van Creveld syndrome. Current treatment options vary widely and depend on which body system is affected and severity of symptoms and complications. Complications of Ellis-van Creveld syndrome include breathing difficulty, congenital heart disease (CHD), atrial septal defect (ASD), kidney disease, and bone abnormalities.
Fragile x syndrome: Currently, there is no known cure for fragile X syndrome, however, there are a variety of ways to help minimize the symptoms of the condition. Education, behavioral or physical therapy, and medication may give children the best chance of using their individual capabilities and skills. Those with significant mental retardation may master many self-help skills. Early intervention gives children the best start possible and the best chance of developing their full potential.
Gigantism: In Gigantism, surgery and radiation may be used to treat symptoms. Surgery is curative in about 80% of cases of pituitary tumors with well-defined borders. For situations in which surgery cannot completely remove the tumor, medication may be used, such as somatostatin analogs, which reduce growth hormone secretion. Dopamine agonists (bromocriptine mesylate, cabergoline) have also been used to reduce growth hormone secretion, but are generally less effective. Recently, pegvisomant, a medication that blocks the effect of growth hormone, has become available. Radiation therapy has been used to normalize growth hormone levels. Drawbacks to radiation therapy are that it can take 5-10 years for the full effects to be seen and is almost always associated with deficiencies in other pituitary hormones. Additionally, radiation has been associated with learning disabilities, obesity, and emotional changes in children. Many experts use radiation only if surgery and medication fail.
Growth hormone deficiency (GHD): Various medications may be used to treat GHD. If left untreated, extremely short stature and delayed puberty will result from this condition. In the past, some patients acquired Creutzfeldt-Jacob disease (the human form of "mad cow" disease) from human-derived growth hormone that was used to treat growth deficiencies. This medication has been removed from the market. Synthetic growth hormone is used instead and does not carry risk of infectious disease.
Neurofibromatosis: Treatment for neurofibromatosis may include surgery, radiation, or chemotherapy. Complications of NF1 neurofibromatosis include disfigurement, scoliosis, learning disabilities, large heads, optic gliomas, and congenital defects of bone. NF1 can result in disfigurement in a number of ways. Skin neurofibromas may develop on the face or on exposed areas of the arms or legs. Larger and deeper plexiform neurofibromas may grow around the eye or eyelid, and may affect the growth of one side of the face. Evidence that diet, exercise, or vitamins affect the growth of neurofibromas is currently lacking. Support and discussion groups may be helpful to those who are upset by the problems of disfigurement. Plastic surgery may also be an option. Plexiform neurofibromas around the eye are often managed jointly by an eye (ophthalmic) surgeon and a plastic surgeon. Children with NF1 should have routine eye examinations by an ophthalmologist, neurologist, or physician familiar with this problem.
Panhypopituitarism: Hypopituitarism is usually permanent and requires life-long treatment; however, a normal life span can be expected. Drug therapy may be used but may also cause side effects.
Russell Silver syndrome: Treatments for Russell Silver syndrome include physical therapy, special education, nutritional therapy, and growth hormone replacement. Russell Silver syndrome may cause self esteem and emotional problems related to appearance, chewing or speaking difficulty if the jaw is very small, and learning disabilities. Older children and adults do not show typical features as clearly as infants or younger children. Intelligence may be normal, although the patient may have a learning disability.
Sotos syndrome: There is currently no known single or standard treatment for Sotos syndrome and available treatment options are focused on alleviation of symptoms. Sotos syndrome is not a life-threatening disorder and patients may have a normal life expectancy. The initial abnormalities of Sotos syndrome usually resolve as the growth rate becomes normal after the first few years of life. Developmental delays may improve in the school-age years, however, coordination problems may persist into adulthood.