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Genetic Drift And The Founder Effect:

Eastern Pennsylvania is home to beautiful farmlands and countryside, but it's also a gold mine of information for geneticists, who have studied the region's Amish culture for decades. Because of their closed population stemming from a small number of German immigrants -- about 200 individuals -- the Amish carry unusual concentrations of gene mutations that cause a number of otherwise rare inherited disorders, including forms of dwarfism.

One form of dwarfism, Ellis-van Creveld syndrome, involves not only short stature but polydactyly (extra fingers or toes), abnormalities of the nails and teeth, and, in about half of individuals, a hole between the two upper chambers of the heart. The syndrome is common in the Amish because of the "founder effect."

When a small part of a population moves to a new locale, or when the population is reduced to a small size because of some environmental change, the genes of the "founders" of the new society are disproportionately frequent in the resulting population.

If individuals in the group tend to marry within it, there's a greater likelihood that the recessive genes of the founders will come together in the cells that produce offspring. Thus diseases of recessive genes, which require two copies of the gene to cause the disease, will show up more frequently than they would if the population married outside the group.

In the Amish, in fact, Ellis-van Creveld syndrome has been traced back to one couple, Samuel King and his wife, who came to the area in 1744. The mutated gene that causes the syndrome was passed along from the Kings and their offspring, and today it is many times more common in the Amish population than in the American population at large.

The founder effect is an extreme example of "genetic drift." Genes occurring at a certain frequency in the larger population will occur at a different frequency -- more or less often -- in a smaller subset of that population. As in the example of human diseases, genetically determined traits that would ordinarily be uncommon in the overall gene pool might crop up with distressing frequency in a small subset of that pool.

Dwarfism

Overview

Dwarfism is short stature that results from a genetic or medical condition. Dwarfism is generally defined as an adult height of 4 feet 10 inches (147 centimeters) or less. The average adult height among people with dwarfism is 4 feet (122 cm).

Many different medical conditions cause dwarfism. In general, the disorders are divided into two broad categories:

Disproportionate dwarfism. If body size is disproportionate, some parts of the body are small, and others are of average size or above-average size. Disorders causing disproportionate dwarfism inhibit the development of bones.

Proportionate dwarfism. A body is proportionately small if all parts of the body are small to the same degree and appear to be proportioned like a body of average stature. Medical conditions present at birth or appearing in early childhood limit overall growth and development.

Some people prefer the term "short stature" or "little people" rather than "dwarf" or "dwarfism." So it's important to be sensitive to the preference of someone who has this disorder. Short stature disorders do not include familial short stature -- short height that's considered a normal variation with normal bone development.

Symptoms

Signs and symptoms -- other than short stature -- vary considerably across the spectrum of disorders.

Disproportionate dwarfism

Most people with dwarfism have disorders that cause disproportionately short stature. Usually, this means that a person has an average-size trunk and very short limbs, but some people may have a very short trunk and shortened (but disproportionately large) limbs. In these disorders, the head is disproportionately large compared with the body.

Almost all people with disproportionate dwarfism have normal intellectual capacities. Rare exceptions are usually the result of a secondary factor, such as excess fluid around the brain (hydrocephalus).

The most common cause of dwarfism is a disorder called achondroplasia, which causes disproportionately short stature. This disorder usually results in the following:

An average-size trunk

Short arms and legs, with particularly short upper arms and upper legs

Short fingers, often with a wide separation between the middle and ring fingers

Limited mobility at the elbows

A disproportionately large head, with a prominent forehead and a flattened bridge of the nose

Progressive development of bowed legs

Progressive development of swayed lower back

An adult height around 4 feet (122 cm)

Another cause of disproportionate dwarfism is a rare disorder called spondyloepiphyseal dysplasia congenita (SEDC). Signs may include:

A very short trunk

A short neck

Shortened arms and legs

Average-size hands and feet

Broad, rounded chest

Slightly flattened cheekbones

Opening in the roof of the mouth (cleft palate)

Hip deformities that result in thighbones turning inward

A foot that's twisted or out of shape

Instability of the neck bones

Progressive hunching curvature of the upper spine

Progressive development of swayed lower back

Vision and hearing problems

Arthritis and problems with joint movement

Adult height ranging from 3 feet (91 cm) to just over 4 feet (122 cm)

Proportionate dwarfism

Proportionate dwarfism results from medical conditions present at birth or appearing in early childhood that limit overall growth and development. So the head, trunk and limbs are all small, but they're proportionate to each other. Because these disorders affect overall growth, many of them result in poor development of one or more body systems.

Growth hormone deficiency is a relatively common cause of proportionate dwarfism. It occurs when the pituitary gland fails to produce an adequate supply of growth hormone, which is essential for normal childhood growth. Signs include:

Height below the third percentile on standard pediatric growth charts

Growth rate slower than expected for age

Delayed or no sexual development during the teen years

When to see a doctor

Signs and symptoms of disproportionate dwarfism are often present at birth or in early infancy. Proportionate dwarfism may not be immediately apparent. See your child's doctor if you have any concerns about your child's growth or overall development.

Causes

Most dwarfism-related conditions are genetic disorders, but the causes of some disorders are unknown. Most occurrences of dwarfism result from a random genetic mutation in either the father's sperm or the mother's egg rather than from either parent's complete genetic makeup.

Achondroplasia

About 80 percent of people with achondroplasia are born to parents of average height. A person with achondroplasia and with two average-size parents received one mutated copy of the gene associated with the disorder and one normal copy of the gene. A person with the disorder may pass along either a mutated or normal copy to his or her own children.

Turner syndrome

Turner syndrome, a condition that affects only girls and women, results when a sex chromosome (the X chromosome) is missing or partially missing. A female inherits an X chromosome from each parent. A girl with Turner syndrome has only one fully functioning copy of the female sex chromosome rather than two.

Growth hormone deficiency

The cause of growth hormone deficiency can sometimes be traced to a genetic mutation or injury, but for most people with the disorder, no cause can be identified.

Other causes

Other causes of dwarfism include other genetic disorders, deficiencies in other hormones or poor nutrition. Sometimes the cause is unknown.

Complications

Complications of dwarfism-related disorders can vary greatly, but some complications are common to a number of conditions.

Disproportionate dwarfism

The characteristic features of the skull, spine and limbs shared by most forms of disproportionate dwarfism result in some common problems:

Delays in motor skills development, such as sitting up, crawling and walking

Frequent ear infections and risk of hearing loss

Bowing of the legs

Difficulty breathing during sleep (sleep apnea)

Pressure on the spinal cord at the base of the skull

Excess fluid around the brain (hydrocephalus)

Crowded teeth

Progressive severe hunching or swaying of the back with back pain or problems breathing

Narrowing of the channel in the lower spine (spinal stenosis), resulting in pressure on the spinal cord and subsequent pain or numbness in the legs

Arthritis

Weight gain that can further complicate problems with joints and the spine and place pressure on nerves

Proportionate dwarfism

With proportionate dwarfism, problems in growth and development often result in complications with poorly developed organs. For example, heart problems that often occur with Turner syndrome can have a significant effect on health. An absence of sexual maturation associated with growth hormone deficiency or Turner syndrome affects both physical development and social functioning.

Pregnancy

Women with disproportionate dwarfism may develop respiratory problems during pregnancy. A C-section (cesarean delivery) is almost always necessary because the size and shape of the pelvis doesn't allow for successful vaginal delivery.

Public perceptions

Most people with dwarfism prefer not to be labeled by a condition. However, some people may refer to themselves as dwarfs, little people or people of short stature. The word "midget" is generally considered an offensive term.

People of average height may have misconceptions about people with dwarfism. And the portrayal of people with dwarfism in modern movies often includes stereotypes. Misconceptions can impact a person's self-esteem and limit opportunities for success in school or employment.

Children with dwarfism are particularly vulnerable to teasing and ridicule from classmates. Because dwarfism is relatively uncommon, children may feel isolated from their peers.

Diagnosis

Your pediatrician will likely examine a number of factors to assess your child's growth and determine whether he or she has a dwarfism-related disorder. In some cases, disproportionate dwarfism may be suspected during a prenatal ultrasound if very short limbs disproportionate to the trunk are noted.

Diagnostic tests may include:

Measurements. A regular part of a well-baby medical exam is the measurement of height, weight and head circumference. At each visit, your pediatrician will plot these measurements on a chart to show your child's current percentile ranking for each one. This is important for identifying abnormal growth, such as delayed growth or a disproportionately large head. If any trends in these charts are a concern, your pediatrician may make more-frequent measurements.

Appearance. Many distinct facial and skeletal features are associated with each of several dwarfism disorders. Your child's appearance also may help your pediatrician to make a diagnosis.

Imaging technology. Your doctor may order imaging studies, such as X-rays, because certain abnormalities of the skull and skeleton can indicate which disorder your child may have. Various imaging devices may also reveal delayed maturation of bones, as is the case in growth hormone deficiency. A magnetic resonance imaging (MRI) scan may reveal abnormalities of the pituitary gland or hypothalamus, both of which play a role in hormone function.

Genetic tests. Genetic tests are available for many of the known causal genes of dwarfism-related disorders, but these tests often aren't necessary to make an accurate diagnosis. Your doctor is likely to suggest a test only to distinguish among possible diagnoses when other evidence is unclear or as a part of further family planning. If your pediatrician believes your daughter may have Turner syndrome, then a special lab test may be done that assesses the X chromosomes extracted from blood cells.

Family history. Your pediatrician may take a history of stature in siblings, parents, grandparents or other relatives to help determine whether the average range of height in your family includes short stature.

Hormone tests. Your doctor may order tests that assess levels of growth hormone or other hormones that are critical for childhood growth and development.

Health care team

A number of disorders causing dwarfism can cause a variety of developmental problems and medical complications. Several specialists may be involved in screening for specific conditions, making diagnoses, recommending treatments and providing care. This team may evolve as your child's needs change, and your family doctor or pediatrician can coordinate the care.

Specialists in your care team may include:

Hormone disorder specialist (endocrinologist)

Ear, nose and throat (ENT) specialist

Specialist in skeletal disorders (orthopedist)

Specialist in genetic disorders (medical geneticist)

Heart specialist (cardiologist)

Eye specialist (ophthalmologist)

Mental health provider, such as a psychologist or psychiatrist

Nervous system abnormalities specialist (neurologist)

Dental specialist in correcting problems with teeth alignment (orthodontist)

Developmental therapist, who specializes in therapy to help your child develop age-appropriate behaviors, social skills and interpersonal skills

Occupational therapist, who specializes in therapy to develop everyday skills and to use adaptive products that help with everyday activities

Treatment

The goal of treatment is to maximize functioning and independence. Most dwarfism treatments don't increase stature but may correct or relieve problems caused by complications.

Surgical treatments

Surgical procedures that may correct problems in people with disproportionate dwarfism include:

Correcting the direction in which bones are growing

Stabilizing and correcting the shape of the spine

Increasing the size of the opening in bones of the spine (vertebrae) to alleviate pressure on the spinal cord

Placing a shunt to remove excess fluid around the brain (hydrocephalus), if it occurs

Hormone therapy

For individuals with dwarfism due to growth hormone deficiency, treatment with injections of a synthetic version of the hormone may increase final height. In most cases, children receive daily injections for several years until they reach a maximum adult height -- often within the average adult range for their family.

Treatment may continue throughout the teen years and early adulthood to ensure adult maturation, such as appropriate gain in muscle or fat. Some individuals may need lifelong therapy. The treatment may be supplemented with other related hormones if they are also deficient.

Treatment for girls with Turner syndrome also requires estrogen and related hormone therapy in order for them to begin puberty and achieve adult sexual development. Estrogen replacement therapy usually continues throughout life until women with Turner syndrome reach the average age of menopause.

Growth hormone supplementation for children with achondroplasia does not increase final adult height.

Ongoing health care

Regular checkups and ongoing care by a doctor familiar with dwarfism can improve quality of life. Because of the range of symptoms and complications, treatments are tailored to address problems as they occur, such as assessment and treatment for ear infections, spinal stenosis or sleep apnea.

Adults with dwarfism should continue to be monitored and treated for problems that occur throughout life.

Limb lengthening

Some people with dwarfism choose to undergo surgery called extended limb lengthening. This procedure is controversial for many people with dwarfism because, as with all surgeries, there are risks. Waiting to decide about limb lengthening until the person with dwarfism is old enough to participate in the decision is recommended because of the emotional and physical stress involved with multiple procedures.

Lifestyle and home remedies

Talk with your pediatrician or a specialist about at-home care. Issues particularly critical for children with disproportionate dwarfism include:

Car seats. Use an infant car seat with firm back and neck supports. Continue using a car seat in the rear-facing direction to the highest weight and height possible (and beyond the recommended age limit).

Infant carriers and play equipment. Avoid infant devices -- such as swings, umbrella strollers, carrying slings, jumper seats and backpack carriers -- that don't support the neck or that curve the back into a C shape.

Adequate head and neck support. Support your child's head and neck when he or she is seated by holding the head, neck and upper back in a safe and stable position. Padding can help to provide the right position and support.

Complications. Monitor your child for signs of complications, such as ear infection or sleep apnea.

Posture. Promote good posture by providing a pillow for the lower back and a footstool when your child is sitting.

Healthy diet. Begin healthy-eating habits early to avoid later problems with weight gain.

Healthy activities. Encourage participation in appropriate recreational activities, such as swimming or bicycling, but avoid sports that involve collision or impact, such as football, diving or gymnastics.

Coping and support

If your child has dwarfism, you can take a number of steps to help him or her cope with challenges and function independently:

Seek help. The nonprofit organization Little People of America provides social support, information about disorders, advocacy opportunities and resources. Many people with dwarfism stay actively involved in this organization throughout their lives.

Modify your home. Make changes to your home, such as putting specially designed extensions on light switches, installing lower handrails in stairways and replacing doorknobs with levers. The Little People of America website provides links to companies that sell adaptive products, such as size-appropriate furniture and everyday household tools.

Provide personal adaptive tools. Everyday activities and self-care can be a problem with limited arm reach and problems with dexterity. The Little People of America website provides links to companies that sell adaptive personal products and clothing. An occupational therapist also may be able to recommend appropriate tools for home and school use.

Talk to educators. Talk to school personnel about what dwarfism is, how it affects your child, what needs your child may have in the classroom and how the school can help meet those needs.

Talk about teasing. Encourage your child to talk to you about his or her feelings, and practice responses to insensitive questions and teasing. If your child tells you that bullying occurs in school, seek help from your child's teacher, principal or the school guidance counselor and ask for a copy of the school's policy on bullying.

Preparing for an appointment

How you learn whether your child has dwarfism will depend on the degree to which it affects his or her development. Disproportionate dwarfism is usually apparent at birth or early in infancy. Proportionate dwarfism may not be diagnosed until later in childhood or the teenage years if your child isn't growing at an expected rate.

Well-baby visits and annual checkups

It's important to take your child to all regularly scheduled well-baby visits and annual appointments throughout childhood. These visits are an opportunity for your child's doctor to track growth, note delays in expected growth and identify other problems in physical development.

Questions your child's doctor may ask include:

What concerns do you have about your child's growth or development?

How well does he or she eat?

Is your child reaching certain milestones in development, such as rolling over, pushing up, sitting up, crawling, walking or speaking?

Are other members of the family very short, or have others experienced growth delays?

Do you have your child's height marked on a measuring chart that you brought with you?

Do you have photographs of your child at various ages that you brought with you?

Talking to your doctor about dwarfism

If your family doctor or pediatrician believes that your child exhibits signs of dwarfism, you may want to discuss these questions:

What diagnostic tests will be needed?

When will we learn the results of the tests?

What specialists will we need to see?

How will you screen for disorders or complications that are commonly associated with the type of dwarfism affecting my child?

How will you monitor my child's health and development?

Can you suggest educational materials and local support services for dwarfism?

Preparing and anticipating questions will help you make the most of your appointment time.

©2023 Mayo Foundation for Medical Education and Research (MRMER). All rights reserved.

10 Celebrities With Real Genetic Mutations

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The 'Bride Wars' actress has a unique physical feature, extra toes. Hudson possesses polydactyly, a condition characterized by having more than the usual number of fingers or toes. Polydactyly is caused by genetic mutations in multiple genes and can occur even without a family history of the condition.

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