Chromosomal Disorders and Inborn Errors of Metabolism

Chromosomal Disorders and Inborn Errors of
Metabolism and stuff ...

Acquired Immunodeficiency Syndrome (AIDS) Ultimately fatal to both mother and infant; severe infections,
progressive motor and cognitive deficits, recurrent diarrhea, failure to thrive, acute weight loss, sepsis, meningitis,
pneumonia, internal organ abscesses, bone and joint infections, chronic otitis media, hearing loss, eye infections, visual
impairment, cold sores, thrush, malignant lymphomas, congestive heart failure, anemia, kidney failure. Maternal
condition

Cerebral Palsy a disorder of movement and posture due to a nonprogressive defect of the
immature brain. Brain damage causes CP, and it manifests in mental retardation, seizures,
visual and auditory deficits, behavior problems, paralysis, CP can be caused by teratogens,
genetic syndromes, chromosomal abnormalities, brain malformations, intrauterine infections,
problems with the placenta, preeclampsia, labor and delivery problems, sepsis, asphyxia,
prematurity, meningitis, traumatic brain injury, toxins, anoxia.

(Congenital) Rubella Syndrome Intrauterine growth
retardation, mental retardation, microcephaly, cataracts,
sensorineural hearing loss, chorioretinitis, congenital heart
disease. Cause: maternal infection with rubella prior to 17th week
of gestation. Inheritance: Not inherited. Incidence: 1/10,000 in areas
where vaccination s are widely administered; higher in
unvaccinated populations. Associated complications: glaucoma,
cataracts, hematological problems, death, diabetes mellitus,
mental retardation, cerebral palsy, blindness, deafness.

Cri du Chat Syndrome pre- and postnatal growth retardation, cat-like cry in infancy,
mental retardation, congenital heart defects, microcephaly, simian creases, hypertelorism
with downward slant, low-set ears, micrognathia, learning disabilities, severe respiratory and
feeding abnormalities in infancy, hypotonia, inguinal hernias, severe-to-profound mental
retardation, sleep disturbance, hyperactivity. Caused by a partial deletion of chromosome 5p15,
usually a new mutation or sporadic. Amniocentesis or chromosome analysis can be used for
prenatal diagnosis. Inheritance: if mother carries a chromosomal abnormality, risk to patient's
siblings is 15% to 25%. If father carries the translocation, 8%. If parents' chromosomes appear
normal, actual risk is unknown, but low. Incidence: 1/20,000; recurrence risk, low unless parent
carries a chromosomal translocation or other chromosomal abnormality.

Cystic Fibrosis An autosomal recessive disorder of the secretory glands leading to malabsorption and lung disease.
The baby may have a salty taste to his/her skin; blockage in the bowel, foul-smelling greasy stool, delayed growth, thick sputum,
coughing or wheezing, frequent chest and sinus infections, bronchitis, pneumonia, polyps in the nasal passages,
cirrhosis of the liver, rectal prolapse, clubbing of the fingertips and toes.

Cytomegalovirus (CMV) Might masquerade as a flu or a mononucleosis-like illness; infants may have hearing loss or
neurological deficits, microcephaly, mental retardation. Maternal disease, passed perinatally.

Down Syndrome Genetic cause of mental retardation in which an extra chromosome is
present on the 21st chromosome pair. Individuals with this are usually short in stature, have straight
hair, slanting eyelids, and may have hearing disabilities, h ypotonia, flat facial profile, mental
retardation, small nose with low nasal bridge, simian creases, congenital heart disease. Caused
by T risomy 21 (94%), mosaicism (2.4%), and translocation (3.6%); new mutation (sporadic).
Associated complications: atlantoaxial instability, ligamentous laxity, strabismus, nystagmus,
cataracts, glaucoma, seizures, leukemia, thyroid abnormalities, recurrent respiratory tract
infections, obesity, depression, inappropriate behavior, premature senility, expressive language
delay, rate of development slows with age. Prenatally diagnosis possible with amniocentesis or
chorionic villus sampling and chromosome analysis. Inheritance is age-related (maternal);
incidence: For women 45 years old or older, the incidence is 1 in 32 compared to 1 in 2,000 for
women between 20 and 25 years old. In women ~ 35 years old, the risk of trisomy 21 (1 in 400) as
well as the possibility of other chromosomal abnormalities is considered significant enough to warrant routine prenatal diagnostics.
For women younger than 35 who have already had one child with T risomy 21, the recurrence risk increases to 1 in 100.
Recurrence risk: in simple T risomy 21, risk to patient's siblings is related to maternal age. If young, 1% to 2%; higher if mother is
older. If cause is translocation, risk is higher.

Duchenne Muscular Dystrophy progressive pelvic muscle weakness and atrophy,
enlargement of thigh muscles, tight heel cords. Patients develop progressive respiratory difficulty,
heart failure, often mild mental retardation. Elevated serum creatine kinase. Survival beyond
young adulthood is unusual. Caused by a mutation in dystrophin gene located on the short arm of
the X chromosome. Inheritance usually X-linked recessive, rare autosomal recessive form.
Associated complications are contractures, scoliosis, wheelchair dependence (usually by age
10 --12), progressive weakness, pneumonia, EKG abnormalities, mild mental retardation or
learning disabilities, hypotonia, delays in motor milestone achievement. Prenatal diagnosis
possible following determination of the child's gender by amniocentesis, use of dystropin cDNA
probes for deletion identification and linkage of DMD markers and DMD gene. Incidence: 1/3,300 in United States; recurrence
risk, male offspring of XLR carrier mother, 50%.

Fetal Alcohol Spectrum Disorder Pre- and postnatal growth retardation, mild-to-
moderate mental retardation, microcephaly, small eyes with droopy eyelids, maxillary
hypoplasia, long philtrum, joint abnormalities, congenital heart disease. Cause: Maternal
ingestion of alcohol during pregnancy. Associated complications: joint contractures, cardiac
abnormalities, myopia, strabismus, hearing loss, dental malocclusion, eustachian tube
dysfunction, mental retardation, fine motor dysfunction, poor eye-hand coordination,
hyperactivity, distractibility, short attention span, speech delays.

Fragile X Syndrome Hereditary form of mental retardation, most apparent in males, that has been
associated with an unusual "fragile" site on the X chromosome. It is thought to be the most common
hereditary form of mental retardation in males. Associated physical features: prominent jaw, large ears,
large testes, ADHD, autism, moderate to severe mental retardation (males) (less for females), and mild
connective tissue abnormalities. Cause: defect in X chromosome. Inheritance: X-linked recessive.
Incidence 1/2,000 male births, 1/4000 female births. Associated complications: pervasive developmental
disorder, communication disorder, behavior problems, hyperactivity, autistic features, joint
abnormalities, mitral valve prolapse.

Hemophilia Hereditary (X-linked) recessive disease characterized
by faulty blood clotting.

Herpes Virus Growth delay, skin vesicles and scarring, retinal
lesions, microcephaly, brain atrophy. Maternal condition, passed to
baby in birth canal.

Klinefelter Syndrome (XXY Syndrome) Occurs only in males. Tall, thin stature, low to normal intelligence, long limbs,
thin appearance, small penis and testes, gynecomastia, infertility, behavior problems. Cause: Chromosomal nondisjunction,
resulting in 47,XXY constitution. Inheritance: Due to nondisjunction. Incidence: 1/500 liveborn males. Associated complications:
inadequate testosterone production, diabetes mellitus, scoliosis, infertility, behavior problems, psychological and psychiatric
abnormalities, 15% -- 20% have IQs below 80, delays in language acquisition and articulation, intention tremor, osteoporosis and
reduced muscle strength, vascular problems.

Phenylketonuria (PKU) an inborn error of amino acid metabolism without acute symptoms; mental retardation,
microcephaly, abnormal gait, and seizures may develop in untreated individuals. Untreated patients often have blond hair and
blue eyes. Treated individuals have still been found to have mild mental retardation especially in executive function. Associated
complications: behavioral disturbances, cataracts, skin disorders, movement disorders. Caused by a deficiency in the enzyme
phenylalanine hydroxylase, which is associated with a mutation in the PAH gene located on chromosome 12q24.1; autosomal
recessive.

Prader-Willi Syndrome short stature, failure to thrive in infancy, hyperphagia
(abnormally increased appetite), almond shaped eyes, viscous (thick) saliva,
hypotonia (particularly in the neck region), hypogonadism with cryptorchidism,
small hands and feet, hypopigmentation, mild to moderate mental retardation,
behavior problems (tantrums, obsessive compulsive disorder, rigidity, food stealing,
skin picking), obstructive sleep apnea, high pain threshold, osteoporosis, neonatal
temperature instability, type 2 diabetes. Cause: approximately 75% have a
microdeletion on the long arm of the paternally inherited chromosome 15
(15q11 --q13); 25% have maternal uniparental disomy; new mutation with autosomal
dominant inheritance when passed from an affected individual; a cause of deaf-blindness.

Rh Factor -- Rh Sensitization Changes that occur when an Rh+ baby's blood enters and Rh-mother's bloodstream. This
predisposes subsequent Rh + babies to kernicterus (mental retardation, choreoathetoid cerebral palsy, staining of
secondary teeth, upward gaze paralysis, high- frequency hearing loss; spastic quadriplegia, deafness, severe mental
retardation, hearing impairment). Sensitization is prevented by the use of the drug Rhogam.

Sickle Cell Anemia A disorder in the production of hemoglobin, the pigment in blood. One nucleotide is substituted for
another, thymine for adenine, in the gene that directs the production of hemoglobin. The triplet code is misread, and the resulting
hemoglobin is defective, causing the formation of sickle-shaped red blood cells, which are fragile and have shortened life spans,
leading to anemia, jaundice, and the formation of gallstones. This disorder also leads to lung damage, pain in the arms,
legs,chest, and abdomen, stroke, priapism, damage to the spleen, liver, and kidneys, and recurrent infections. Inheritance:
autosomal recessive.

Tay-Sachs Disease Progressive nervous system disorder, deafness, blindness, seizures, rapidly
fatal, usually by 4 years of age. Development is normal for the first several months of life; then increased
startle response, hypotonia followed by hypertonia, cherry-red spot in muculae, optic nerve atrophy.
Cause: Deficiency of enzyme hexosaminidase A caused by a mutation in the gene at chromosome 15.
Inheritance: autosomal recessive. Associated complications: feeding abnormalities, aspiration,
progressive neurological deterioration. More common in Ashkenazic Jewish population. A child with Tay-
Sachs initially develops normally. At about 6 months, the child's health begins to deteriorate. He or she can
no longer sit or babble and soon becomes blind and has severe mental retardation. There is a rapid
decline and fatality by about 4 or 5 years. In adult form, it presents with ataxia. Incidence: 1/112,000; 1/3,800
in Ashkenazi Jewish population; increased frequency in the Cajun and French Canadian population.

TORCH Infections T oxoplasmosis, S yphilis, R ubella, C ytomegalovirus (CMV), and H erpesvirus.

Toxemia A disorder of late pregnancy -- mother's feet, ankles, arms, hands swell, blood pressure rises, kidneys begin
functioning poorly, protein in urine. Puts the baby and the mother at medical risk, and babies must be born quickly to assuage the
disorder. Babies may be born prematurely or at low-birth-weight.

Toxoplasmosis An infectious disease caused by a microorganism. It may be asymptomatic in adults, but can lead to severe
fetal malformations in infants; microcephaly, hydrocephalus, cataracts, blindness, deafness, mental retardation, calcified
regions of the brain.

Trisomy 13 Microphthalmia, cleft lip and palate, and polydactyly, dysmorphic appearance (i.e., low
set ears, hypertelorism, scalp defects), microcephaly, brain malformations, congenital heart defects,
flexion deformity of fingers, eye abnormalities, kidney and gastrointestinal tract malformations, coloboma,
corneal opacity. Cause: nondisjunction resulting in an extra # 13 chromosome. Inheritance: new mutation.
Incidence: 1/8,000 births. Associated complications: multi-organ system involvement, profound mental
retardation, visual impairment, cerebral palsy, sensorineural hearing loss.

Trisomy 18 Small for gestational age, low-set ears, clenched hands with overriding
fingers, congenital heart defects, microphthalmia, coloboma, corneal opacity, 30%
die within the first month of life; 50% by second month, and only 10% survive the first year.
Cause: nondisjunction resulting in trisomy for chromosome # 18. Inheritance: new
mutation. Incidence: 1/6,600. Associated complications: feeding problems, aspiration,
diaphragmatic hernia, conductive hearing loss, mental retardation. Also called
Edward Syndrome.

Turner Syndrome (XO syndrome) Affects females only; short stature, broad chest with widely
spaced nipples, short appearing neck with extra skin folds at back of neck, "puffy" hands and feet,
congenital heart disease, ovarian dysgenesis, resulting in infertility, usually normal intelligence.
Cause: Chromosomal nondisjunction resulting in a single X chromosome. Inheritance: new mutation.
Incidence: 1/2,000. Associated complications: coarctation of the aorta or other types of congenital
heart disease, thyroid abnormalities, diabetes mellitus, kidney abnormalities, learning disabilities,
"streak" ovaries causing infertility and delaying puberty, small ear canals, eye involvement (strabismus,
ptosis, nystagmus, cataracts), chronic otitis media in 90% with frequent hearing loss.

XYY Syndrome Subtle abnormalities, including tall stature, poor fine motor coordination, aggressive behavior, severe acne,
large teeth. Cause: chromosomal nondisjunction. Inheritance: new mutation. Incidence: 1/1,000. Associated complications:
slow nerve conduction velocities, tall stature, large teeth, IQ in the same range as siblings, learning disabilities, particularly
with language, decreased speed of information processing, impaired sensorimotor integration skills, and possible behavior
problems (tantrums and aggression), increased risk for autism.

47XXX (trisomy X), XXXX (tetrasomy X), XXXXX (pentasomy X) syndromes Females with XXX
syndrome generally have above-average stature but otherwise typical physical appearance; 70% have significant learning
disabilities and language delay/problems are also present sometimes. Significant malformations have been described in some
patients including gonadal dysgenesis (nonfunctional ovaries), dysmorphic facial appearance, absent or shrunken kidneys, and
vaginal and uterine malformations. XXXX syndrome is associated with a mildly unusual facial appearance, behavioral problems,
and moderate mental retardation. XXXXX syndrome is associated with severe mental retardation and multiple physical
defects. Cause: nondisjunction during meiosis. Inheritance: new mutation. Incidence 1/8000 live female births. Associated
complications: infertility, delayed pubertal development.

Other sex-chromosome abnormalities 48 XXXY, 48XXYY, and 49XXXYY syndromes The presence of
a single Y chromosome, even with a number of X chromosomes, results in a male. Abnormal physical, sexual, and mental
development characterizes all of these syndromes. Compared to Turner (45X), Klinefelter (47XXY), and XYY syndromes (with
a combined incidence of 1 in 300) these other disorders are extremely rare.