Growth abnormalities

• 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.

• 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). Café-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 (café) with milk (lait) because of their light tan color. In darker-skinned people, café-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 (café) 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.

• 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.

A

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.

B

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.

C

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.

D

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®.