Common Chromosomal and Genetic Disorders in Children

by T. M McDevitt|J. E. Ormrod
Source: Pearson Allyn Bacon Prentice Hall
Topics: Genetic, Chromosomal, and Metabolic Conditions

Chromosome Abnormalities

Children with chromosome abnormalities are born with an irregular number of chromosomes (more than or fewer than 46) or with one or more chromosomes that have irregular structures (deletions from or duplications to parts of an individual chromosome, or with a part of one chromosome moved to another location).

Down Syndrome

Incidence

1 per 700-1,000 births

Characteristics^a

Children with Down syndrome have one extra chromosome. Physical characteristics include a protruding tongue, thick lips, flat nose, short neck, wide gaps between toes, short fingers, specific health problems, and risks for heart problems and hearing loss. Mental retardation can range from mild to severe. Children often have good visual discrimination skills and may be better at understanding verbal language than producing it.

Implications for Care

Provide explicit instruction in any delayed skills (e.g., in language). Address health issues such as heart problems and potential feeding difficulties.

Klinefelter Syndrome

Incidence

1 per 500-1,000 boys

Characteristics^a

Only boys have Klinefelter syndrome; they have one Y chromosome and two X chromosomes. Diagnosis may not occur until adolescence, when testes fail to enlarge. Affected boys tend to have long legs, to grow modest breast tissue, a/1d to remain sterile. They tend to show lower than average verbal ability and some speech and language delays.

Implications for Care

Offer an enriched verbal environment. Medical treatment may be given to support development of male sexual characteristics.

Turner Syndrome

Incidence

1 per 2,500-5,000 girls

Characteristics^a

Only girls have Turner syndrome; they have one X chromosome and are missing the second sex chromosome. Affected girls have broad chests, webbed necks, short stature, and specific health problems. They do not show normal sexual development. They may show normal verbal ability but lower than average ability in processing visual and spatial information.

Implications for Care

Provide instruction and support related to visual and spatial processing. Hormone therapy helps with bone growth and development of female characteristics.

Prader-Willi Syndrome

Incidence

1 per 10,000-25,000 births

Characteristics^a

A deletion from a gene segment on chromosome 15 is inherited from the father. Children with this syndrome tend to become obese and show mental retardation; they also have small hands and feet and are short in stature. They may develop maladaptive behaviors such as throwing frequent temper tantrums and picking at their own skin. Beginning at ages 1-6, children may eat excessively, hoard food, and eat unappealing substances.

Implications for Care

Create developmentally appropriate plans to help children regulate eating, decrease inappropriate behaviors, and increase acceptable emotional expression. Seek medical care as necessary.

Angelman Syndrome

Incidence

1 per 10,000-30,000 births

Characteristics^a

A deletion from a gene segment on chromosome 1 5 is inherited from the mother. Children with this syndrome show mental retardation, a small head, seizures, and jerky movements. They have unusual, recurrent bouts of laughter not associated with happiness.

Implications for Care

Provide appropriate educational support suited to children's skills and developmental levels. Seek medical care as necessary.

Single-Gene Defects

Children with single-gene defects have a problem on a dominant gene (an error on one of the 22 paired chromosomes, that is, on any chromosome except X or Y^b), a recessive defect on both chromosomes in One of the 22 matched pairs, or a problem in a recessive gene on the X chromosome (boys) or a problem in a gene on both X chromosomes (girls).

Neurofibromatosis

Incidence

Mild form occurs in 1 per 2,500-4,000 births; severe form occurs in 1 per 40,000-50,000 births

Characteristics^a

Children with this dominant-gene defect develop benign and malignant tumors in the central nervous system. The condition may be caused by an error in a gene that would normally suppress tumor growth. Learning disabilities are somewhat common and mental retardation occurs occasionally. Most individuals experience only minor symptoms, such as having colored and elevated spots on their skin.

Implications for Care

Address learning disabilities; offer adaptive services to children with mental retardation. Tumors may need to be removed or treated. Surgery or braces may be needed if the spine becomes twisted.

Huntington Disease (HD)

Incidence

3 to 7 per 100,000 births

Characteristics^a

Children with this dominant-gene defect develop a progressive disorder of the central nervous system. Signs typically appear by age 35 to 45, though age of first symptoms has varied between 2 and 85 years. HD may be caused by the production of a protein that destroys brain cells. Early signs include irritability, clumsiness, depression, and forgetfulness. Eventually, loss of control over movements of arms, legs, torso, or facial muscles occurs, speech becomes slurred, and severe mental disturbances arise.

Implications for Care

Remove sharp edges from the physical environment. When memory deteriorates, provide visual instructions about daily tasks. Medication may be given to alleviate movement problems and depression.

Phenylketonuria (PKU)

Incidence

1 per 15,000 births, with rates highest in people of Celtic origin (e.g., from Ireland and Scotland)

Characteristics^a

Children with this recessive-gene defect are at risk for developing mental retardation, eczema, seizures, and motor and behavioral problems such as aggression, self-mutilation, and impulsiveness. When children have both recessive genes for PKU, their livers cannot produce an enzyme that breaks down phenylalanine (an amino acid); this substance accumulates and becomes toxic to the brain.

Implications for Care

Provide educational materials to enhance planning and memory skills and compensate for limitations. When phenylalanine is restricted from diet, children develop much more normally, and mental retardation is avoided. Subtle problems may still result (e.g., awkward pencil grip and learning disabilities).

Sickle Cell Disease

Incidence

1 per 500-600 children of African (Black) descent; rates are also elevated in people of Mediterranean descent

Characteristics^a

Children with this recessive-gene defect develop problems with blood circulation. The disease causes red blood cells to grow rigid, and passage of blood through small vessels causes pain. Children may experience many serious conditions, including stroke, infection, tissue damage, and fatigue. Symptoms become obvious during the first or second year of life.

Implications for Care

Be alert to medical crises, such as strokes. Offer comfort to children who are tired or in pain. Treatments include blood transfusions, medication for pain and infections, and other medicines to reduce frequency of medical crises.

Cystic Fibrosis (CF)

Incidence

1 per 3,300 children from European American backgrounds and 1 per 9,500 children from Hispanic American backgrounds

Characteristics^a

Children with this recessive-gene defect have glands that produce large amounts of abnormally thick, sticky mucus, which creates serious problems for breathing and digestion. CF is usually noticed in infancy due to persistent coughing, wheezing, pneumonia, and big appetite with little weight gain. Many individuals with CF now live well into their 40s.

Implications for Care

Be aware of symptoms that require medical care. The condition is often treated with physical therapy, medication, and bronchial drainage.

Tay-Sachs Disease

Incidence

1 per 2,500-3,600 children among Ashkenazi Jews (of Eastern European ancestry)

Characteristics^a

Children with this recessive-gene defect develop a fatal, degenerative condition of the central nervous system. They lack an enzyme required to break down a fatty substance in brain cells. At about 6 months of age, children slow down in development, lose vision, display an abnormal startle response, and go into convulsions. Other functions are gradually lost, and children become mentally retarded, cannot move, and die by age 3 or 4.

Implications for Care

Offer love and attention as you would to other children. Be alert to new accommodations that may be needed in the environment, such as stabilizing and securing the surroundings when children lose sight. There is no known cure or treatment.

Thalassemia (Cooley's Anemia)

Incidence

1 in 800-2,500 individuals of Greek or Italian descent in the U.S.; rates are lower in other groups

Characteristics^a

Children with this recessive-gene defect develop a disease of blood cells in which oxygen is not transmitted effectively. They become pale, fatigued, and irritable within their first 2 years of life. Individuals with serious forms of the condition may develop feeding problems, diarrhea, and enlargement of the spleen and heart, infections, and unusual facial features and bone structures. Young people severely impaired by this condition sometimes die by early adulthood.

Implications for Care

Help children to cope with their health problems. Treatment may include blood transfusions, antibiotics, and occasionally bone marrow transplants.

Duchenne Muscular Dystrophy

Incidence

1 per 3,000 to 4,000 boys

Characteristics^a

Only boys acquire this X-linked recessive-gene defect, which causes a progressive muscular weakness because of a gene's failure to produce an essential protein needed by muscle cells. Between ages 2 and 5, affected boys begin to stumble and walk on their toes or with another unusual gait. They may lose the ability to walk between ages 8 and 14 and may later die from respiratory and cardiac problems.

Implications for Care

Watch for respiratory infections and heart problems. Treatments include physical therapy, orthopedic devices, surgery, and medications to reduce muscle stiffness.

Notes

^aThis table describes typical symptoms for children with particular chromosomal and genetic problems. Children's actual level of functioning depends on the medical treatments they receive; their experiences with families, teachers, other caregivers, and other children; and their health and other genes they might possess. New medical treatments and educational interventions are constantly being tested, and many will increase quality of life for these children.

^bX-linked dominant defects also occur but are rare. For example, children who receive the gene for Hypophosphatemia on the X chromosome produce low levels of phosphate and. a result, have soft bones that are easily deformed.

Sources: Blachford, 2002; Burns et al., 2000; Cody & Kamphaus, 1999; Dykens & Cassidy, 1999; Massimini, 2000; K. L. Moore & Persaud, 2003; Nilsson & Bradford, 1999; M. P. ""I & Schulte, 1999; J. T. Smith, 1999; Waisbren, 1999; Wynbrandt & Ludman, 2000.

Credits to Lee Phooi Yin (T4)

Intelligence: More Nature Than Nurture?

ScienceDaily (Oct. 17, 2007) — While showing an impressive growth prenatally, the human brain is not completed at birth. There is considerable brain growth during childhood with dynamic changes taking place in the human brain throughout life, probably for adaptation to our environments.

Evidence is accumulating that brain structure is under considerable genetic influence [Peper et al., 2007]. Puberty, the transitional phase from childhood into adulthood, involves changes in brain morphology that may be essential to optimal adult functioning. Around the onset of puberty gray matter volume starts to decrease, while white matter volume is still increasing [Giedd et al., 1999].

Recent findings have shown, that variation in total gray and white matter volume of the adult human brain is primarily (70--90%) genetically determined [Baare et al, 2001] and in a recent magnetic resonance imaging (MRI) brain study with 45 monozygotic and 61 dizygotic 9-year-old twin-pairs, and their 87 full siblings also high heritabilities have been found [Peper et al, in preparation]. Thus, while environmental influences may play a role in later stages during puberty, around the onset of puberty brain volumes are already highly heritable.

Hilleke Hulshoff Pol presents persuasive evidence how genetic factors influence the brain structure opening new insights into the reciprocal gene-environment developmental pathways.

Genetic influences

Twin studies have also shown that genetic effects vary regionally within the brain, with high heritabilities of frontal lobe volumes (90--95%), moderate estimates in the hippocampus (40--69%), and environmental factors influencing several medial brain areas.

However, the mechanisms by which interaction between genes and environment occur throughout life as well as dynamics of brain structure and its association with brain functioning still remain unknown. Twin and family studies and newly evolving genetic approaches start to give us a glimpse as to which genes and (interacting) environmental influences are shaping our brains.

Brain structure -- measured macroscopically using MRI -- and the dynamic changes therein, have a functional relevance.

Studies revealed that total brain volume is positively correlated with general intelligence. In healthy subjects, the level of intellectual functioning has been positively associated with whole brain, gray, and white matter volumes [Thompson et al, 2001; Posthuma et al, 2002]. More focally, several brain areas were found to be correlated with intelligence. Interestingly, it was also shown that the trajectory changes in cortical thickness throughout adolescence are associated with the level of intelligence.

Furthermore, a common set of genes may also cause the association between brain structure and cognitive functions. However, in elderly twins, the associations between frontotemporal brain volumes and executive function were found to be because of common environmental influences shared by twins from the same family [Carmelli et al., 2002].

These results point to the possibility that overlapping sets of genes or common environmental influences cause variation in two distinct phenotypes. It might be, for example, that a higher level of cognitive functioning leads a person to select an environment that also increases brain size. The genetic influence on brain size then simply reflects the genetic influences on cognition. Thus, the specific mechanism, pathways, and genes that are involved in human brain morphology and its association with cognitive functions remain elusive.

Although genetic effects on morphology of specific gray matter areas in the brain have been studied, the heritability of focal white matter was unknown until recently. Similarly, it was unresolved whether there is a common genetic origin of focal gray matter and white matter structures with intelligence. In our study involving 54 monozygotic and 58 dizygotic twin pairs and their 34 singleton siblings, verbal, and performal intelligence were found to share a common genetic origin with an anatomical neural network involving the frontal, occipital, and parahippocampal gray matter and connecting white matter of the superior occipitofrontal fascicle, and the corpus callosum [Hulshoff Pol et al., 2006].

For the genetic analyses, structural equation modeling and voxel-based morphometry were used. To explore the common genetic origin of focal gray matter and white matter areas with intelligence, cross-trait/cross-twin correlations were obtained in which the focal gray matter and white matter densities of each twin are correlated with the psychometric intelligence quotient of his/her cotwin.

The results of this study indicate that genes significantly influence white matter density of the superior occipitofrontal fascicle, corpus callosum, optic radiation, and corticospinal tract, as well as gray matter density of the medial frontal, superior frontal, superior temporal, occipital, postcentral, posterior cingulate, and parahippocampal cortices. Moreover, the results show that intelligence shares a common genetic origin with superior occipitofrontal, callosal, and left optical radiation white matter and frontal, occipital, and parahippocampal gray matter (phenotypic correlations up to 0.35).

These findings point to a neural network that shares a common genetic origin with human intelligence. Thus, it seems that the individual variation in morphology of areas involved in attention, language, visual, and emotional processing, as well as in sensorimotor processing are strongly genetically influenced.

In addition, unique environmental factors influenced vast gray matter and white matter areas surrounding the lateral ventricles (up to 0.50). This finding coincides with the significant environmental influences on lateral ventricle volume [common (0.58) and unique (0.42) with no significant contributions of genes] that was reported previously in this twin sample [Baaré et al., 2001].

Clinical implications

Considering the high heritabilities for global brain volumes and particular focal brain densities and thicknesses, the search for genes that are involved in brain growth, aging, and brain structure maintenance is important. Such knowledge can help us understand normal developmental and age-associated changes in individual variation in brain functioning.

Moreover, it enhances our knowledge of individual variation in brain functioning and facilitates the interpretation of the morphological changes found in psychiatric disorders such as schizophrenia [van Haren et al., 2007]. Also, it allows future efforts to find particular genes responsible for brain structures to be concentrated in areas that are under considerable genetic influence [Hulshoff Pol et al., 2006].

A genetic approach to find genes involved in brain structure that has been applied in several studies is that of diseases with a clear genetic etiology such as Huntington's disease, Down syndrome, Williams syndrome, and Velocardiofacial syndrome. A review reveals for these diseases besides disease specific brain changes, decreases in total brain, white matter, and hippocampus volumes, irrespective of the genes and/or chromosomes involved. This suggests that many genes are probably involved in the individual variation of these measures [Peper et al., in press].

It is important to investigate which environmental factors have an influence on the expression of genes (as found in DNA-methylation). Additionally, the study of interaction between genes and environmental factors is warranted. Furthermore, the simultaneous effects of multiple genes and possibly the interaction among genes, also needs investigation as the high heritability of a complex quantitative phenotype such as brain volume cannot be explained by a single-gene polymorphism.

Conclusion

MRI studies in twins indicate that, given the basic additive genetic model, overall brain volume in adulthood is highly heritable.

To test for influences of genetic, common, and unique environmental factors or interactions between genetic and environmental influences. twin studies carried out in large and more homogenous samples, analyzed with advanced quantitative genetic methods are needed.

To investigate the stability of genetic and environmental influences onto functional neural networks in human brain longitudinal twin studies in childhood as well as in adulthood are needed since brain volume changes dynamically throughout life.

New brain-imaging methods, such as DTI-fiber tracking and resting state functional MRI, allow to study the heritability of neural networks underlying brain functioning.

These new methods, in coherence with new genetic approaches, will enable us to further disentangle which genes and environmental factors and interactions therein influence human brain structure throughout life.

Where do your genes come from?

Credits to Chok Yuh Ping, T5

This is where you are formed

This is where you are formed:

Human Egg with Coronal Cells
This image is of a purple, colour-enhanced human egg sitting on a pin. The egg is coated with the zona pellicuda, a glycoprotein that protects the egg but also helps to trap and bind sperm. Two coronal cells are attached to the zona pellicuda.

Sperm on the Surface of a Human Egg

Here's a close-up of a number of sperm trying to fertilize an egg.

Human Embryo and Sperm

It looks like the world at war, but it is actually five days after the fertilisation of an egg, with some remaining sperm cells still sticking around. This fluorescent image was captured using a confocal microscope. The embryo and sperm cell nuclei are stained purple while sperm tails are green. The blue areas are gap junctions, which form connections between the cells.

Coloured Image of a 6 day old Human Embryo Implanting

by Margaret Lim ~

Gregor Mendel's Punnett Squares

credits to HuanLing

Where do your genes come from?