MICRO-CEPHALY

What is microcephaly?

Microcephaly is a condition that is present at birth in which the baby’s head is much smaller than normal for an infant of that age and gender. “Micro” means small and cephaly refers to head. Most children with microcephaly also have a small brain and mental retardation. However, some children with small heads have normal intelligence.

What causes microcephaly?

Microcephaly is either caused by exposure to harmful substance during the fetal development, or it may be associated with genetic problems or syndromes that may have a tendency to run in families.

Theories suggest that the following ay predispose a fetus to problems that affect the normal development of the head during pregnancy:

• Exposure to hazardous chemicals/substance
• Exposure to retardation
• Lack of proper vitamins and nutrients in the diet
• Infection
• Prescription or illegal drug and alcohol consumption
• Maternal diabetes

Microcephaly can occur alone or in association with other health problems, and may occur from inheritance of an auto-somal recessive, or rarely, an auto-somal dominant gene. Acquired microcephaly may occur after birth due to various brains injuries such as lack of oxygen or infection.

Auto-somal recessive and auto-somal dominant are to patterns in which genes are inherited in a family. Genes determine out traits, such as eye color and blood type, and can also cause disease. Auto-somal means that both males and females are equally affected. Recessive means that two copies of the gene, one inherited from each parent, are necessary to have the condition (in this case, microcephaly). After parents have had one child with auto-somal recessive microcephaly, there is a 25 percent chance, or one in

four chances, with each pregnancy, to have another child with microcephaly.

What are symptoms of Microcephaly?

The following are the most common symptoms of microcephaly. However, each child may experience symptoms differently. Symptoms may include:

• Appearance of the baby’s head is very small
• High-pitched cry
• Poor feeding
• Seizures
• Increased movement of the arms and legs (spasticity)
• Developmental delays
• Mental retardation

The symptoms of microcephaly may resemble other conditions or medical problems. Always consult your child’s physician for a diagnosis.

How is microcephaly diagnosed?

Microcephaly may be diagnosed before the birth by prenatal ultrasound, a diagnostic imaging technique which uses the high frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view the internal organs as they function, and to assess the blood flow through various vessels.

In many cases, microcephaly may not be evident by ultrasound until the third trimester, and therefore may not be seen on ultrasound preformed earlier in pregnancy. The diagnosis of microcephaly may be made at birth or later in the infancy. The baby’s head circumference is much smaller than normal. During the physical examination, the physician obtains a complete prenatal and birth history of the child. In older babies and children, the physician may also risk if there are a family history of the microcephaly or others medical problems. The physician will also ask about developmental milestones since microcephaly can be associated with other problems, such as mental retardation. Developmental delays may require further medical follow up for underlying problems.

A measurement of the circumference of the child’s head is taken and compared to a scale that can identify normal and abnormal ranges.

Diagnostic tests that may be performed to confirm the diagnosis of microcephaly and identify abnormalities in the brain include:

• Head circumference – this measurement is compared with a scale for normal growth and size
• X-ray – a diagnostic test which uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.
• Computed tomography scan (also called a CT or a CAT scan). – A diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including bones, muscles, fat and organs. CT scan are more detailed than the x-rays.
• Magnetic resonance imaging (MRI) – a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.
• Blood tests
• Urine tests

Life-long considerations for a child with microcephaly:

There is no treatment for microcephaly that will return the baby’s head to a normal size or shape. Since microcephaly is a life-long condition that is not correctable, management includes focusing on preventing or minimizing deformities and maximizing the child’s capabilities at home and in the community. Positive reinforcement will encourage the child to strengthen his/her self-esteem and promote as much independence as possible.

The full extent of the problem is usually not completely understood immediately after birth, but may be revealed as the child grows and develops.

Children born with microcephaly require frequent examination and diagnostic testing by their physician to monitor the development of the head as the child grows. The medical team work hard with the child’s family to provide education and guidance to improve the health and well being of the child.

Genetic counseling may be recommended by the physician to provide information on the recurrence risks for the disorder and any available testing.

MANIFESTATIONS BEFORE THE AGE OF EIGHTEEN

Mental retardation is present from childhood. It can be caused by any condition which impairs development of the brain before, during, or after birth. The causes are numerous: hereditary factors; genetic abnormalities (e.g. Down’s syndrome); poor prenatal care; infections during pregnancy; abnormal delivery; illness during infancy; toxic substances )e.g. consumption of alcohol by the pregnant mother; exposure of the child to lead, mercury or other environmental toxins); physical abuse; and malnutrition, among others. Regardless of the cause, part of the definition of mental retardation is that it manifests itself during an individual’s developmental period, usually deemed to be birth through age eighteen. Many psychiatrists argue that the age before which signs of retardation must become manifest should be raised from eighteen to twenty-two, to reflect the difficulties in obtaining accurate age records for many people with this disability and the differing rates at which people develop.

An ordinary adult cannot suddenly “become” mentally retarded. An adult may, for reasons related to accident or illness, suffer a catastrophic loss in intellectual functioning and adaptive skills, but this would not make him or her “mentally retarded.” Since by definition mental retardation starts during childhood. One implications of this is that mental retardation is virtually impossible for an adult to fake: when evaluating whether an adult is mentally retarded, testers look not only at I.Q. test results, but also at school reports, childhood test records, and other evidence that would show whether his or her intellectual and adaptive problems developed during childhood.

Early diagnosis can help the person with mental retardation obtain access to appropriate special education, training, clinical programs, and social services during important developmental years – as well as through life. With help from family, social workers, teachers, and friends, many mentally retarded people succeed in simple jobs, maintain their own households, marry, and give birth to children of normal intelligence. But, although support and services can improve the life functioning and opportunities for a person with retardation, they cannot cure the condition. There is no “Cure’ or mental retardation.

FACTORS IN LIFESTYLES OR ENVIRONMENT

One study has reported an association between low socioeconomics status and holo-prosencephaly risk. However, this observation has not been confirmed.

A case-control study found a suggestion of an association between cytogenetically normal holo-prosencephaly and maternal alcohol consumption during early pregnancy. Maternal smoking, respiratory illness medications, and salicylate-containing medication have also shown tera-togenic effects (Coren 2000). However, some of these associations were not statistically significant. Another study reported no significant link between alcohol, smoking, or x-ray exposure and holo-prosencephaly risk (Cohen 1989). An investigation failed identifies any significant association between holo-prosencephaly and proximity to various types of industry (Castilla 2000).

Maternal diabetes has been reported by several studies to increase holo-prosencephaly (Becerra 1990). It should be noticed that diabetes causes a series of metabolic disturbances, and these disturbances interfere with fetal development. Other metabolic disturbances, including cholesterol production, can affect the sonic Hedgehog (Shh) signaling pathway (Cohen 2002).

Other maternal factors that have been tentatively associated with holo-prosencephaly, based on anecdotal evidence or studies involving small numbers of cases, include retinoic acid, salicylate, estrogen/progestin, anticonvulsant, weight reduction diets and/or low maternal weight, previous pregnancy loss, and congenital infection with cytomegalovirus, rubella, and toxoplasmosis (Croen 1996).  One survey that involved a small number of cases failed to identify any association between holo-prosencephaly and retinoic acid (De Wals 1991). A case-control study suggests that risk of holo-prosencephaly may be increased with maternal use of misoprostol, a synthetic prostaglandin used for elective termination (Orioli 2000).

There is no information available about the use of multivitamins and folic acid to reduce the incidence of holo-prosencephaly (Czeizel 2004). Maternal residence and vicinity to solid waste incinerators or landfills does not increase the incidence of holo-prosencephaly (Cordier 2004), nor does maternal exposure to pesticides (Berkowitz 2003), biological solvents (Wennborg 2005), or marijuana (Fried 2000).

Prevalence

Birth prevalence in the United States for hypo-plastic left heart syndrome is no currently known. The rate in Texas for 1999-2002 deliveries was 1.21 cases per 10,000 live births (Texas Department of State Health Services 2005). Differences in prevalence may be due to differences in case inclusion criteria.

Diagnosis, Treatment and Prevention of Mental Retardation

Diagnosis

If mental retardation is suspected, a comprehensive physical examination and medical history should be done immediately to discover any organic cause of symptoms. Such conditions as hyperthyroidism and PKU are treatable. If these conditions are discovered early, the progression of retardation can be stopped and, in some cases, partially reversed. If a neurological or neurophychologist for testing.

A complete medical, family, social, and educational history is compiled from existing medical and school records (if applicable) and from interviews with parents. Children are given intelligence tests to measure their learning abilities and intellectual functioning. Such tests include the Stanford-Binet Intelligence

Scale, the Wechsler Intelligence scales, the Wechsler Preschool and Primary scale of Intelligence, and the Kaufman Assessment battery for Children. For infants, the Bayley Scales of Infant Development may be used to access motor, language, and problem-solving skills. Interviews with parents or other caregivers are used to access the child’s daily living, muscle control, communication, and social skills. The Woodcock-Johnson Scales of Independent Behavior and the Vineland Adaptive Behavior Scales (VABS) are frequently used to evaluate these skills.

Treatment

Federal legislation entitles mentally retarded children to free testing and appropriate, individualized education and skills training within the school system from ages three to 21. For children under age of three, many states have established early intervention programs that assess children, make recommendation, and begin treatment programs. Many day school are available to help train retarded children in such basic skills as bathing and feeding themselves.

Extracurricular activities and social programs are also important in helping retarded children and adolescents gain self-esteem.

Training n independent living and job skills is often begun in early adulthood.

The level of training depends on the degree of retardation. Mildly retarded people can often acquire the skills needed to live independently and hold an outside job. Moderate to profoundly retarded persons usually require supervised community living in a group home or other residential setting.

Family therapy can help relatives of the mentally retarded develop coping skills. It can also help parents deal with feeling of guilt or anger. A supportive, warm home environment is essential to help mentally retarded reach their full potential.

Prognosis

People with meld to moderate mental retardation are frequently able to achieve some self-sufficiency and to lead happy and fulfilling lives. To reach these goals, they need appropriate and consistent educational, community, social, family and vocational supports. The outlook is less promising for those with severe to profound retardation. Studies have shown that these persons have a shortened life expectancy. The diseases that are usually associated with severe retardation may cause the shorter life span. People with Down syndrome will develop the brain changes that characterize Alzheimer’s disease in later life and may develop the clinical symptoms of this disease as well.

Prevention

Immunization against disease such as measles and Hib prevents many of the illness that can cause mental retardation. In addition, all children should undergo routine developmental screening as part of their pediatric care. Screening is particularly critical for those children who may be neglected or undernourished or may live in disease-producing condition. Newborn screening and immediate treatment for PKU and hyperthyroidism can usually catch these disorders early enough to prevent retardation.

Good prenatal care can also help prevent mental retardation. Pregnant women should be educated about the risks of alcohol consumption and the need to maintain good nutrition during pregnancy. Such tests as amniocentesis and Ultrasonography can determine whether a fetus is developing normally in the womb.

** DOWN SYNDROME **

Down syndrome or trisomy 21 (in British its called Down’s syndrome) is a genetic condition resulting from the presence of all or part of an extra 21^st chromosome. Down syndrome is characterized by a combination of major and minor abnormalities of body structure and function. Among features present in nearly all cases are impairment of learning and physical growth, and a recognizable facial appearance usually identified at birth. It is named after John Langdon Down, the British doctor who first described it in 1866.

Individuals with Down syndrome have lower than average cognitive ability, normally ranging from mild to moderate retardation. Some individuals may have low intelligence overall, but will generally have some amount of developmental disability, such as a tendency toward concrete thinking or naiveté. There are also a small number of individuals with Down syndrome with severe to profound mental retardation. The incidence of Down syndrome is estimated at 1 per 800 to 1 per 1000 births.

The common physical features of Down’s syndrome also appear in people with a standard set of chromosomes. They include a simian crease (a single crease across one or both palms), almond shaped eyes, shorter limbs, speech impairment, and protruding tongue. Health concerns for individuals with Down syndrome include a higher risk for congenital heart defects, gastro-esophageal reflux disease, recurrent ear infections, obstructive sleep apnea, and thyroid dysfunctions.

Early childhood intervention, screening for common problems, medical treatment where indicated, a conductive family environment, and vocational training can improve the overall development of children with Down syndrome. While some of the genetic limitations of Down syndrome cannot be overcome, education and proper care, initiated at any time, can improve quality of life.

History

Down syndrome is firstly characterized by English physician John Langdon Down as a distinct from of mental retardation in 1862, and in a more widely published report in 1866 entitles “Observation on an ethnic classification of idiots”. Due to John Langdon’s perception that children with Down syndrome shared physical facial similarities with those of Blumenbach’s Mongolian race, Down used terms such as mongolism and Mongolian idiocy. Idiocy was a medical term used at that time to refer to a severe degree of intellectual impairment. Down wrote that mongolism represented “retrogression”, the appearance of Mongoloid traits in the children of allegedly more advanced Caucasian parents.

By the 20^th century, Mongolian idiocy had become the most recognizable form of mental retardation. Most people with it were institutionalized. Few of the associated medical problems were treated, and most died in infancy or early adult life. With the rise of the eugenics movement, 22 of the 48 United States and a number of countries began programs of involuntary sterilization of individuals with Down syndrome and comparable degree of disability. The ultimate expression of this type of public policy was the German euthanasia program Aktion T-4 begun in 1940. Court challenges and public revulsion led to discontinuation or repeal of such programs during the decades after World War II.

Until the middle of the 20^th century, the cause of Down syndrome remained unknown, although the presence in all races the association with older maternal

Age, and the rarity of recurrence had been noticed. Standard medical texts assumed it was due to combination of inheritable factors which had not been identified. Other theories focused on injuries sustained during birth.

With the discovery of Karyotype techniques in the 1950s it became possible to identify abnormalities of chromosomal number or shape. In 1959, Professor Jerome Lejeune discovered that Down syndrome result from an extra chromosome. The extra chromosome was subsequently labeled as the 21^st,  and the condition as trisomy 21.

In 1961, a group of nineteen geneticists wrote to the editor of The Lancet suggesting that Mongolian idiocy had misleading can-notations, had become as embarrassing term, and should changed. The lancet supported Down’s syndrome. The World Health Organization (WHO) officially dropped references to mongolism in 1965 after a request by the Mongolian delegate.

In 1975, the United States National Institute of Health convened a conference to standardize the nomenclature of malformations. They recommended eliminating the possessive form: “the possessive use of an eponym should be discontinued, since the author neither had nor owned the disorder. While both the possessive and non-possessive forms are used in the general population, Down syndrome is the accepted term among professionals in the USA, Canada and other countries, While Down syndrome continues to be used in the United Kingdom and other areas.

Characteristics of Down syndrome

Example with Down syndrome may have some or all of the following physical characteristics: oblige eye fissures with small skin folds on the inner corner of the eyes, muscle hypotonia, a flat nasal bridge, a single palmar fold (simian crease), a protruding tongue (due to small oral cavity, poor muscle tone, and an enlarged tongue near the tonsils), a short neck, white spots on the iris known as Brush-field spots, excessive flexibility in joints, congenital heart defects, excessive space between large and second toe, and a single flexion furrow of the fifth finger. Most individuals with Down syndrome have mental retardation n the mild (IQ 50-70) to moderate range (IQ 35-50), with scores for children with Mosaic Down syndrome (explained below) some 10-30 points higher. In addition, individuals with Down syndrome can have serious abnormalities affecting any body system.

Cognitive development

Cognitive development in children with Down syndrome is quite variable. Many can be successful in school, while others struggle. Because of this variability in expression of Down syndrome, it is important to evaluate children individually. The cognitive problems that are found among children with Down syndrome can also be found among typical children. This means that parents can take advantage of general programs that are offered through the schools or other means. Children with Down syndrome have a wide range of abilities. It is not possible at birth to predict their capabilities. The identification of the best methods of teaching each particular child ideally begins soon after birth through early intervention programs.

Language skills show a difference between understanding speech and expressing speech. It is common for children with Down syndrome to need speech therapy to help with expressive language. Fine motor skills are delayed and often lag behind gross motor skills and can interfere with cognitive development. Occupational therapy can address these issues.

In education, mainstreaming of children with Down syndrome is controversial. Mainstreaming is when students of differing abilities are placed in classes with their chronological peers. Children with Down syndrome do not age emotionally/socially and intellectually at the same rates as children with out Down syndrome, so eventually the intellectual and emotional gap between children with as with out Down syndrome widens. Complex thinking as required in sciences but also in history, the arts, and the other subjects is often beyond their abilities, or achieved much later than in most children. Therefore, if they are to benefit from mainstreaming without feeling inferior most of the time, special adjustments must be made to the curriculum.

Some European countries such as Germany and Denmark advise two-teacher system, whereby the second teacher takes over a group of children with disabilities within the class. A popular alternative is cooperation between special education schools and mainstream schools. In cooperation, the core subjects are taught in separate a class, which neither slows down the typical students nor neglects the students with disabilities. Social activities, outgoings, and any sports and arts activities are performed together, as are all breaks and meals.

Health

The medical consequences of the extra material in DS are highly variable and may affect the function of any organ system or bodily process. The health aspects of Down syndrome encompass anticipating and preventing effects of the condition, recognizing complications of the disorder, managing individual symptoms, and assisting the individual and his/her family in coping and thriving with any retarded disability or illness

The most common manifestation of Down syndrome are the characteristics facial features, cognitive impairment, congenital heart disease, hearing deficits, short stature, thyroid disorders, and Alzheimer’s disease. Other less common serious illness includes leukemia, immune deficiencies, and epilepsy. Down syndrome can result from several different genetic mechanisms. This results in a wide variability in individual symptoms due to complex gene and environment interactions. Prior to birth, it is not possible to predict the symptoms that an individual with Down syndrome will develop. Some problems are present at birth, such as certain heart malformations. Others become apparent over time, such as epilepsy.

These factors contribute to a significantly shorter lifespan for people with Down syndrome. One study, carried out in United States, shows an average lifespan of 49 years.

Genetic research

 Down syndrome disorders are based on having too many copes of the genes located on chromosome 21. in general, this leads to an over-expression of the genes. Understanding the genes involved may help to target the medical treatment to individuals with Down syndrome. It is estimated that chromosome 21 contains 200 to 250 genes. Recent search has identified a region of the chromosome that contains the main genes responsible for the pathogenesis of Down syndrome, located proximal to 21q22.3. The search for major genes involved in Down syndrome characteristics is normally in the region 21q21-21q22.3

Recent use of transgenic mice to study specific genes in the Down syndrome critical region is had yielded some result. APP (Mendelian Inheritance in Man (OOIM) 104760, located at 21q21) is an Amyloid beta A4 precursor protein.

It is suspected to have a major role in cognitive difficulties. Another gene, ETS2 (Mendelian Inheritance in Man (OMIM 164740, located at 21q22.3) is Avian

Erythroblastsis Virus E26 Oncogene Homolog 2. Researchers have “demonstrated that over-expression of ETS2 result in apoptosis. Transgenic mice over-expressing ETS2 developed a smaller thymus and lymphocyte abnormalities, similar to features observed in Down syndrome.

Sociological and Cultural aspects

Advocates for people with Down syndrome points to various factors, such as special education and parental supports groups which make life easier for parents.

There are also great strides being made in education, housing, and social setting to create “Down-friendly” environments. In most developed countries, since the early 20^th century many people with Down syndrome were housed in institutions or colonies and excluded from society. However, in the 21^st century there is a change among parents, educators and other professionals generally advocating a policy of inclusion, bringing people with any form of mental or physical disability into general society as much as possible. In many countries people with Down syndrome are educated in the normal school system and there are increasingly higher quality opportunities to mix special education with regular education settings.

Despite this change, reduced abilities of people with Down syndrome pose a challenge to their parents and families. While living with their parents is preferable to institutionalization for most people wit Down syndrome, they often encounter patronizing attitudes and discrimination in the wider community. In the past decade, many couples with Down syndrome have married and started homes of their own, overcoming many of the stereotypes associated with this condition.

The first World Down Syndrome Day was held on 21 March 2006. The day and month were chosen to correspond with 21 and trisomy respectively. It was proclaimed by Down syndrome International.

CAUSES AND SYMPTOMS (Mental Retardation)

Low IQ scores and limitations in adaptive skills are the hallmarks of mental retardation. Aggression, self-injury, and mood disorders are sometimes associated with the disability. The severity of the symptoms and the age at which they first appear depend on the cause. Children who are mentally retarded reach developmental milestones significantly later than expected, if at all. If retardation is caused by chromosomal or other generic disorders, it is often apparent from infancy. If retardation is caused by childhood illness or injuries, learning and adaptive skills that were once easy may suddenly become difficult or impossible to master.

In about 40% of cases, the cause of mental retardation cannot be found. Biological and environmental factors that can cause mental retardation include:

Genetic Factors

About 30% of cases of mental retardation is caused by hereditary factors. Mental retardation may be caused by an inherited genetic abnormality, such as fragile X syndrome. Fragile X, a defect in the chromosome that determines sex, is the most common inherited cause of mental retardation. Single-gene defects such as phenylketonuria (PKU) and other inborn errors of metabolism may also cause mental retardation if they are not discovered and treated early. An accident or mutation in genetic development may also cause retardation. Example of such accidents is development of an extra.

An accident or mutation in genetic development may cause retardation. An example of such a mutation is the development of an extra chromosome 21 that cause Down syndrome.

Prenatal illness and issues

Fetal alcohol syndrome (FAS) affects one in 3,000 children in Western countries. It is caused by the mother’s heavy drinking during the first twelve weeks (trimester) of pregnancy. Some studies have shown that even moderate alcohol use during the pregnancy may cause learning disabilities in children. Drug abuse and cigarette smoking during pregnancy have also been linked to mental retardation.

Maternal infections and such illness as glandular disorders, rubella, toxoplasmosis, and cytomegalovirus (CMV) infection may cause mental retardation. When the mother has high blood pressure (hypertension) or blood poising (toxemia), the flow of oxygen to the fetus may be reduced, causing Brain damage and mental retardation.

Birth defects that cause physical deformities of the head, brain, and central nervous system frequently cause mental retardation. Neural tube defect, for example, is a birth defect in which the neural tube that forms the spinal cord does not close completely. This defect may cause children to develop an accumulation of cerebrospinal fluid inside the skull (hydrocephalus). Hydrocephalus can cause learning impairment by putting pressure on the brain.

Childhood illness and injuries

Hyperthyroidism, whooping cough, chickenpox, measles, and Hib disease

(A bacterial infection) may cause mental retardation if they are not treated adequately. An infection of the membrane conversing the brain (meningitis)

or an inflammation of the brain itself (encephalitis) can cause swelling that in turn may cause brain damage and mental retardation. Traumatic brain injury caused by a blow to the head or by violent shaking of the upper body may also cause brain damage and mental retardation in children.

Environmental factors

Ignored or neglected infants who are not provided with mental retardation and physical stimulation required for normal development may suffer irreversible learning impairment. Children who live in poverty and suffer from malnutrition, unhealthy living conditions, abuse, and improper or inadequate medical care are at a higher risk. Exposure to lead or mercury can also cause mental retardation. Many children have developed lead poisoning from eating the flaking lead-based paint often found in older building.