Muscle, Connective Tissue, and Neonatal Disorders

Chapter Outline

• 17.1 Overview

• 17.2 Achondroplasia

• 17.3 Charcot-Marie-Tooth Syndrome

• 17.4 Duchenne Muscular Dystrophy

• 17.5 Ellis-Van Creveld Syndrome

• 17.6 Amyotrophic Lateral Sclerosis

• 17.7 Marfan Syndrome

• 17.8 Fibrodysplasia Ossificans Progressiva

• 17.9 Myotonic Dystrophy

• 17.10 Angelman Syndrome and Prader-Willi Syndrome

• 17.11 Fragile-X Syndrome

• 17.12 Waardenburg Syndrome

• Chapter Summary

Learning Outcomes

• •

  Identify each genetic disorder affecting each system

• •

  Outline the symptoms of each disorder

• •

  Explain the genetic basis of each disorder

• •

  Summarize the current therapies available to treat each disorder

17.1 Overview

Humans have endoskeletons which are rigid internal body parts made up of bone that receive the applied force of muscles. The skeleton provides the framework and anchor points against which muscles, attached via tendons, can exert force (Figure 1). It is made up of 206 bones divided into 2 systems: a) axial skeleton with skull bones, 12 pairs of ribs, the sternum, and the 26 vertebrae; b) appendicular skeleton which is made up of the pectoral girdles (shoulders); pelvic girdle (hips) and pairs of arms, hands, legs and feet. Bones are complex organs that function in movement, providing support by anchoring muscles, protecting internal organs, storage of minerals particularly calcium and phosphorous, and blood cell production (white blood cells, red blood cells and platelets). There are two types of bone tissue: compact bone which is found in the shaft and at both ends of long bones. Compact bone is made up many thin, cylindrical, dense layers around interconnected canals for blood vessels and nerves and it resists mechanical shock. Spongy bone tissue has abundant air spaces but very firm and is found inside both ends and shaft of bone. Spongy tissue contains red bone marrow where blood cells are formed. It also contains yellow bone marrow which is largely fat but can be converted to red marrow in severe blood loss cases.

Figure 1.

The structure and bones of the human skeleton

Source: Image used under license from Shutterstock.com

Three types of cells involved in making bone. 1) Osteoblasts: In the developing embryo cartilage models are first constructed, into which osteoblasts secrete organic substances which mineralize; cartilage then breaks down to form bone marrow cavities. Once osteoblasts are imprisoned by these secretions, they become osteocytes or mature living bone cells. In adults, large amounts of minerals and many osteocytes are removed and replaced routinely in a process called bone remodeling which adjusts bone strength and maintains calcium and phosphorous levels in the blood. 2) Osteoclasts secrete enzymes that digest bone in the routine bone remodeling activities in the body. 3) Cartilage are collagen fibres embedded in a rubbery matrix of protein and carbohydrate secreted by cells called chondrocytes. In the adult body cartilage is retained in the flexible parts of our skeleton (ears, nose, intervertebral discs, and windpipe). Physical exercise stresses bone such that the process of mineral deposition exceeds withdrawal—making the bones denser and stronger. With age, bones decline in mass where mineral deposits lag behind withdrawal making the bones hollow and brittle—a condition known as osteoporosis.