DWARFISM,GIGANTISM and sign symptoms,causes

It best for identifying dwarfism and genetic problems patient

1. Dwarfism, Gigantism, and Acromegaly

2. Objectives By the end of this lecture, the students will be able to: Define dwarfism gigantism and acromegaly Describe the Pathophysiology of acromegaly and gigantism List the clinical features Elaborate the diagnostic criteria Discuss the medical management 3

3. Which Gland is involved? The Pituitary Gland is a pea- sized gland located at the base of the skull. This gland secretes many hormones and is referred to as the “Master Gland” because it controls hormone functions all over the body. The Pituitary Gland The GH gene is located on chromosome 17 (Chen et al., 1989). 4

4. What is growth hormone A hormone that stimulates growth in animal or plant cells, esp. (in animals) a hormone secreted by the pituitary gland. Growth hormone (GH) is a protein-based peptide hormone. It stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland. 5

5. Major functions of growth hormone Stimulate growth and cell production in humans. It is synthesized, stored, and secreted by the somatotroph cells within pituitary gland. Human growth hormone is used clinically to treat children's growth disorders and adult growth hormone issues. Recently human growth hormones (HGH) have become used against aging and weight loss. 6

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7. how does the growth hormone (gh) normally function? The Anterior Pituitary Gland produces human growth hormone ( hGH or GH), also known as somatotropin . GH binds to receptors on liver cells and they release insulin- like growth factor- 1 (IGF-1). This hormone causes body cells to grow and stimulates protein synthesis within cartilage, bones, and muscle. This hormone increases the growth rate of bones and muscles during childhood. GH also has many effects on metabolism GH stimulates the rate at which amino acids enter cells and protein synthesis occurs. GH stimulates fat and carbohydrate metabolism. 8

8. Negative Feedback loop of the Growth Hormone 9

9. Amount of Growth Hormone 10

10. Dwarfism Hypo secretion of the GH Condition caused by insufficient secretion of growth hormone during childhood. Short limb structure 11 Shortest Man to ever Live: Gul Mohammed: 22.5 inches tall, lived to age 29

11. Cont… 12 Caused by deficiency of Pituitary Gland Limited production of GH, called somatotrophin Growth failure, distorted facial appearance, delayed bone age and many organ problems Shortest Woman to ever Live: Pauline Musters: 23 inches tall, lived to age 19

12. Genetics Diastrophic dysplasia and usually spondyloepiphyseal dysplasias are inherited in a recessive manner. This means a child must receive two copies of the mutated gene -- one from the mother, one from the father -- to be affected. Achondroplasia, on the other hand, is inherited in a dominant manner. That means a child needs only one copy of the mutated gene to have that form of skeletal dysplasia. There is a 25% chance that a child born to a couple in which both members have achondroplasia will be of normal height. But there is also a 25% chance the child will inherit both dwarfism genes, a condition known as double-dominant syndrome. This is a fatal condition that usually results in miscarriage. 13

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16. Young female dwarf standing next to a boy of normal stature 17

17. Classification of Dwarfism Achondroplasia.   Achondroplasia is a form of short-limbed dwarfism. The word achondroplasia literally means "without cartilage formation The most common form of dwarfism, achondroplasia occurs in about one out of 26,000 to 40,000 babies and is evident at birth. People with achondroplasia have a relatively long trunk and shortened upper parts of their arms and legs. Other features of achondroplasia include: A large head with a prominent forehead A flattened bridge of the nose Protruding jaw Crowded and misaligned teeth Forward curvature of the lower spine Curved legs flat, short, broad feet 18

18. Mutations in the FGFR3 gene cause achondroplasia . The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia .

19. Cont… 2. Spondyloepiphyseal dysplasias (SED) . A less common form of dwarfism, SED affects approximately one in 95,000 babies. Spondyloepiphyseal dysplasia refers to a group of conditions characterized by a shortened trunk, which may not become apparent until a child is between 5 and 10 years old. Other features can include: Club feet Cleft palate Severe osteoarthritis in the hips Weak hands and feet Barrel-chested appearance 20

20. 3. Diastrophic dysplasia. An autosomal recessive dysplasia which affects cartilage and bone development. ("Diastrophism" is a general word referring to a twisting. Diastrophic dysplasia is due to mutations in the SLC26A2 gene A rare form of dwarfism, diastrophic dysplasia occurs in about one in 100,000 births. People who have it tend to have shortened forearms and calves (this is known as shortening of the middle of the bone (mesomelic) shortening). Other signs can include Deformed hands and feet Limited range of motion Cleft palate Ears with a cauliflower appearance    21

21. Diagnosis X rays of the long bones Blood tests for growth hormones MRI of the head 22

22. 23 Treatments for Dwarfism Daily injections of Human Growth Hormone (HGH)

23. 24 Gigantism "Pituitary gigantism" and Hyper secretion of the GH Bone growth in an excess amount Can result in “hoarseness, sleep apnea, joint pain, cardiovascular disease, hypertension, insulin resistance, visual impairment and severe headaches” Tallest Man to ever Live: Robert Wadlow: 8’11.1”, lived to age 22 Gene on the X chromosome, GPR101 , which was over expressed 1000-fold more than normal

24. Cont… Overproduction of growth hormone causes excessive growth. In children, the condition is called gigantism. In adults, it is called acromegaly . 25

25. Gigantism is an abnormally large growth due to excess growth hormone during childhood, before growth plates close. 26 Cont…

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27. Clinical features Excessive growth The child is large for their age Delayed puberty Double vision or difficulty with peripheral vision Headaches Increased sweating Large hands and feet Thickening of facial features Weakness 28

28. Investigations CT scan MRI GH raised level IGF-1 raised level 29

29. Treatment Surgery Transsphenoidal surgery to remove the pituitary adenoma Radiation therapy Drug therapy Bromocriptine 30

30. Acromegaly Acromegaly is a hormonal disorder that results when the pituitary gland produces excess growth hormone (GH) After puberty The name acromegaly comes from the Greek words for "extremities" and "enlargement“.

31. Cont... O verproduction of growth hormone causes excessive growth. In children, the condition is called gigantism. In adults, it is called acromegaly . Epidemiology of Acromegaly : Acromegaly is a relatively uncommon disease, and studies estimate that its prevalence is between 50 to 70 cases per million people 32

32. Pathophysiology of Acromegaly Characterized by growth hormone (GH) excess Typically caused by a GH-secreting pituitary adenoma Uncontrolled tumor GH production causes elevated serum IGF-I Increased GH and IGF-I levels cause the signs and symptoms of acromegaly . 33

33. Causes Caused by prolonged overproduction of GH by the pituitary gland. Pituitary tumors Pituitary adenoma Ectopic production of GH by other tumors (e.g., cancers of the pancreas or lung) 34

34. Sign and Symptoms Growth hormone stimulates the growth of bones, muscles, and many internal organs Swelling of the hands and feet Facial features become coarse as bones grow Protruding jaw Voice deepening (Cartilage in the voice box (larynx) may thicken) Enlarged lip, nose, and tongue Degenerative arthritis Thickened ribs (creating a barrel chest) Joint pain Enlarged heart  Offensive body odor Galactorrhea 35

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36. Cont… Enlargement of other organs Snoring Fatigue and weakness Headaches Loss of vision Irregular menstrual cycles in women Increased incidence of obstructive sleep apnea Frontal bossing Thickening of the nose Macroglossia Prognathism Women can have mild hirsutism. 37

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38. Supra orbital ridge 39

39. Investigations X-ray of the skull Show thickening of the bones and enlargement of the nasal sinuses. X-rays of the hands Show thickening of the bones under the fingertips and swelling of the tissue around the bones. Blood sugar Blood sugar levels high 40

40. Treatment Surgery Transsphenoidal surgery to remove the pituitary adenoma Radiation therapy Drug therapy Bromocriptine 41

41. References American Association of Clinical Endocrinologists Medical guidelines for clinical practice for the diagnosis and treatment of acromegaly. Endocrine Practice . 2004;10:213-225. Buehler BR, Henzen CM, de Zulueta MT, Ross RA. Acromegaly and colorectal cancer. J Applied Res. 2004;4:257-260. Melmed S, Kleinberg D. Anterior pituitary. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, eds. Williams Textbook of Endocrinology . 10th ed. Philadelphia Pa.: WB Saunders Company; 2003:177-260. Molitch ME. Clinical manifestations of acromegaly. Endocrinol & Metab Clin North Am . 1992;21:597-614. Melmed S, Casanueva F, Cavagnini F, Chanson P, et al. Consensus statement: Medical management of acromegaly. Eur J Endocrinol . 2005;153:737-740. 42

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