Down Syndrome

Todd T. Eckdahl

• Publisher: Momentum Press
• Year: 2017
• ISBN:
  9781944749620
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

This book presents Down syndrome, which is the most common chromosomal disorder in humans, occurring at a rate of about 1 in 700 births. It describes the characteristic physical features caused by Down syndrome and the myriad of symptoms and health complications it brings, including heart defects, congenital vision and hearing loss, abnormalities of the musculoskeletal system, digestive problems, epilepsy, leukemia, an increased risk of infectious disease, dementia, and intellectual disability. Readers will learn about methods by which Down syndrome can be diagnosed prenatally or at birth, and the cause of Down syndrome as extra copies of the approximately 250 genes on chromosome 21. The book describes treatments and therapies for Down syndrome, and approaches to the education of children with it. Future prospects for the diagnosis and treatment of Down syndrome are presented, including experimental drugs, stem cell therapies, a process by which embryos produced in a clinical laboratory can be screened for Down syndrome before being used to establish a preg­nancy, and several Down syndrome gene therapy strategies.

CHAPTER 1

Symptoms and Diagnosis

Down syndrome is called a syndrome because it affects a wide variety of organ systems. This chapter describes the effects of Down syndrome on physical appearance; catalogs its symptoms, including heart defects, congenital conditions affecting the musculoskeletal, digestive, and immune systems, intellectual disability, and dementia from Alzheimer’s disease; and describes additional health complications caused by Down syndrome. The chapter also explains methods by which Down syndrome can be diagnosed prenatally or after birth.

Down Syndrome Results in Characteristic Physical Features

All of us have physical features that are strongly influenced by our DNA. We have tendencies to resemble our siblings and parents, and members of our extended families. The influence of family background on the appearance of people with Down syndrome is overshadowed by the occurrence of characteristic physical features (see Table 1.1), and the effect is strong enough that people with Down syndrome often appear to be more closely related to each other than to their families. The illusion of a close relationship among people with Down syndrome comes from distinctive facial features, including a more rounded face, upwardly slanted eyes that have pronounced epicanthal folds, a flattened nasal bridge, a small nose, a small mouth with a large tongue that tends to stick out more often, and crooked teeth that are irregularly shaped. The eyes often have lightly or darkly colored spots on the iris, which are called Brushfield spots. People with Down syndrome tend to have small ears that are set lower on the head. The back of the head is often flattened, and the neck is shorter and wider. Characteristic body shape features caused by Down syndrome include short stature, short and stocky arms and legs with hyperflexible joints, and a stomach that sticks out from poor abdominal muscle tone. The hands tend to be broad with short fingers, and only one crease across the palm. The feet often have a larger gap between the first and the second toe.

Table 1.1 Common Down syndrome physical features

Body part	Description
Skull	Small, shortened skull that is flattened on the back, sloping forehead, missing or underdeveloped sinuses
Eyes	Upward slanted and wide-set eyes, epicanthal folds, Brushfield spots
Ears	Smaller ears with extra folds, ears set lower on the head
Nose	Smaller nose, flattened nasal bridge
Mouth	Smaller mouth, large tongue that tends to stick out more often, undersized teeth, crooked teeth, irregularly shaped teeth
Hands	Broad hands, only one crease across the palm, short fingers, curved fifth finger
Feet	Larger gap between the first and the second toe
Limbs	Short and stocky arms and legs with hyperflexible joints
Body	Short stature, shorter and wider neck, protruding stomach

Congenital Heart Defects from Down Syndrome

Down syndrome affects the process by which the fetal heart is formed during pregnancy. All early embryos are divided into three primary germ layers that establish the overall spatial organization of the body and contain the progenitor cells for all tissues and organs. The heart forms during the third week after fertilization from mesoderm, the middle of the three primary germ layers that also gives rise to skeletal muscle, smooth muscle, bone, cartilage, and blood. Mesoderm cells grow, divide, migrate, and communicate with other cells to form a primitive heart that pumps blood throughout the fetal circulatory system to provide nutrients and oxygen to the developing embryo, and remove carbon dioxide and other wastes. The straight tube of cells that forms the primitive heart bends into an “S” shape during the fourth week of development, after which septa develop to separate the heart into four chambers. By week nine post-conception, four valves take shape that control blood flow between the heart chambers, between the heart and the lungs, and between the heart and the rest of the developing embryo. The fully formed heart pumps blood through the circulatory system, which includes arteries to deliver oxygen and nutrients to cells and tissues, and veins to return blood carrying carbon dioxide and waste back to the heart for removal by other organs. The circulatory system has a second circulatory circuit that delivers blood from the heart to the lungs for the exchange of oxygen and carbon dioxide and returns blood to the heart for delivery to the rest of the body.

About 50 percent of all infants born with Down syndrome have some type of heart defect. A common heart defect among Down syndrome infants is atrioventricular septal defect (AVSD), which occurs when the septa that normally separate the chambers of the heart, or the valves that control blood flow between the chambers, fail to develop properly. A complete AVSD incudes a hole in the septum between the two atria, a hole in the septum between the two ventricles, and abnormal valves between the atrial and ventricular chambers. An incomplete AVSD occurs when there is a hole in the atrial septum and one abnormal valve. AVSD reduces the ability of the heart to properly circulate oxygenated blood to the body, and deoxygenated blood to the lungs, which places an extra demand on the heart. The left ventricle normally generates high blood pressure to circulate blood to the whole body, but the hole in the septum between the two ventricles causes an abnormal increase in the pressure of blood in the pulmonary artery that leads to the lungs. The resulting pulmonary hypertension causes the lungs to fill with blood and results in breathing difficulty, increased heart rate, swelling of extremities, and cyanosis, which is a bluish skin color around the mouth, fingers, and toes. The combined effects of AVSD on the heart and lungs often result in congestive heart failure, during which infants develop symptoms such as faster and heavier breathing, sweating, and tiredness that gradually worsen over a period of one or two months. Some infants with a complete AVSD do not develop congestive heart failure because the lungs are protected from increased blood pressure by constricted blood vessels. Constricted blood vessels lead to pulmonary vascular disease because of the reduced capacity to deliver oxygen to tissue throughout the body. Some infants born with Down syndrome have a ventricular septal defect (VSD) or an atrial septal defect (ASD), the severity of which depends on the size and location of the hole in the septum. A small hole may produce no symptoms, whereas larger holes cause breathlessness and poor weight gain. Infants with Down syndrome are sometimes born with patent ductus arteriosus (PDA), which is caused by the abnormal persistence of a fetal channel that connects the pulmonary artery and the aorta prior to birth. The ductus arteriosus directs blood away from the nonfunctioning fetal lungs that do not have access to air yet. At birth, when the lungs fill with air and begin to function, the ductus arteriosus normally closes within one or two days. PDA occurs when the ductus arteriosus remains open, and the consequence is pulmonary hypertension, with symptoms that include breathing difficulty, tiredness, and increased heart rate. Some Down syndrome infants are born with tetralogy of Fallot (TOF), which includes the four congenital heart abnormalities of VSD, narrowing of the passageway to the pulmonary artery, enlargement of the right ventricle, and an enlargement of the valve leading to the aorta. These heart defects cause reduced blood flow to the lungs, which results in rapid breathing and cyanosis.

What Other Congenital Conditions Result from Down Syndrome?

Down syndrome results in congenital conditions that affect a variety of body systems (Table 1.2). More than 60 percent of Down syndrome infants are born with vision problems, such as congenital cataracts that cause the lens of the eye to become opaque and result in sensitivity to bright light, poor night vision, and double vision. The severity of congenital cataracts varies from mild cases of dulled vision to severe cases of complete blindness. Cataracts can also develop during childhood or adulthood. Down syndrome infants are often born with amblyopia, which is commonly called “lazy eye” because one eye does not move normally and makes a much smaller contribution to vision than the other eye. Amblyopia occurs when the brain receives better visual input from one eye than the other eye due to nearsightedness, cataracts, or permanently crossed eyes. The symptoms of amblyopia include blurred vision, double vision, and poor depth perception. Amblyopia often causes the eyes to move independently of one another, instead of coordinately, which compromises depth perception. Down syndrome also produces a higher incidence of refractive errors that are present at birth or develop during childhood, including farsightedness, nearsightedness, and astigmatism. Children and adults with Down syndrome are more likely to need corrective lenses. Down syndrome infants are often born with abnormal tear ducts that easily become clogged, which causes excessive watering of the eyes, or with blepharitis, which is recurrent inflammation of the eyelids. Down syndrome also increases the prevalence of glaucoma, during which abnormal drainage of the fluid inside the eye places pressure on the optic nerve, producing the symptoms of moderate to severe eye pain, eye redness, cloudy vision, and tunnel vision. Glaucoma can lead to permanently blurred vision and eventual blindness.

Table 1.2 Common Down syndrome congenital conditions

Body system	Congenital conditions
Heart	Septal defects (ASD, VSD, AVSD), PDA, TOF
Vision	Refractive errors, cataracts, amblyopia, blepharitis, glaucoma
Hearing	Hearing loss (conductive and sensorineural), glue ear, otitis media
Musculoskeletal	Hypotonia, ligamentous laxity, atlantoaxial instability, hip abnormalities, kneecap instability, flat feet
Digestive	Hirschsprung disease, tracheoesophageal fistula, esophageal atresia, duodenal atresia, imperforate anus, GERD
Immune	Hypothyroidism, celiac disease, respiratory infections

Over 70 percent of Down syndrome infants are born with hearing problems. Hearing problems are categorized as conductive hearing loss when sound waves are not conducted properly from the outer ear to the eardrum and the bones of the middle ear. Sensorineural hearing loss results from dysfunction of the inner ear or its connection to the nervous system. Most cases of hearing loss in Down syndrome infants are conductive hearing loss, which is often caused by an abnormal buildup of wax in the ear canal that prevents the conduction of sound. Down syndrome can cause the development of a smaller ear canal that is more susceptible to wax blockage. Conductive hearing loss in Down syndrome infants can be also caused by glue ear, an abnormal accumulation of fluid in the middle ear, or by otitis media, infection of the middle ear. Glue ear and otitis media prevent the conduction of sound by the tiny bones of the middle ear. Both causes of conductive hearing loss occur because Down syndrome causes abnormal development of the Eustachian tube that normally drains mucus from the middle ear. The cause of sensorineural hearing loss is unknown for most people. The severity of sensorineural hearing loss ranges from mild to profound, and it can cause hearing loss of all sound frequencies, or it can selectively reduce hearing in the high, medium, or low frequency ranges. Sometimes sensorineural hearing loss develops later during childhood. It is important to distinguish between prelingual hearing loss that occurs before a child learns to speak and postlingual hearing loss because they present very different challenges to language acquisition.

Another congenital problem that many Down syndrome infants have is hypotonia, which is the occurrence of weak muscles throughout the body. Infants with hypotonia seem “floppy” because of their weaker muscles, and are often delayed in meeting developmental milestones such as rolling over, sitting up, crawling, and walking. Hypotonia in the mouth and throat makes it difficult for Down syndrome infants to take in and swallow breast milk or formula, and weak muscles throughout the digestive tract impair digestion and can lead to constipation and poor weight gain. Infants with Down syndrome are often born with ligamentous laxity due to loose ligaments in joints throughout the body. Ligamentous laxity impairs the stability of...

Table of contents

• Cover
• Half Title Page
• Title Page
• Copyright Page
• Contents
• Acknowledgments
• Introduction
• Chapter 1 Symptoms and Diagnosis
• Chapter 2 Causes and Contributing Factors
• Chapter 3 Treatment and Therapy
• Chapter 4 Future Prospects
• Conclusion
• Glossary
• Bibliography
• Index