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
failure to thrive, acute weight loss, sepsis, meningitis, pneumonia, internal organ abscesses, bone and joint infections, chronic otitis media, hearing loss, eye
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 intellectual
, 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, intellectual disability, 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
are widely administered; higher in unvaccinated populations. Associated complications:
glaucoma, cataracts, hematological problems, death, diabetes mellitus,
intellectual disability
, cerebral palsy, blindness, deafness.

Cri du Chat Syndrome Pre- and postnatal growth retardation, cat-like cry in infancy, intellectual disability, 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 intellectual disability, sleep disturbance, hyperactivity. Caused by a partial deletion of chromosome 5p15, usually a new mutation or
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,
intellectual disability. Maternal disease, passed perinatally.

Down Syndrome Genetic cause of intellectual disability 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, hypotonia, flat facial profile, intellectual disability, small nose with low nasal bridge, single
palmar crease, congenital heart disease. Caused by Trisomy 21 (94%), mosaicism (2.4%), and translocation (3.6%); new mutation (sporadic). Associated
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
Trisomy 21, the recurrence risk increases to 1 in 100. Recurrence risk: in simple Trisomy 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
intellectual disability. 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
, scoliosis, wheelchair dependence (usually by age 10 --12), progressive weakness, pneumonia, EKG abnormalities, mild intellectual disability 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
carrier mother, 50%.

Fetal Alcohol Spectrum Disorder Pre- and postnatal growth retardation, mild-to-moderate intellectual disability, 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, intellectual disability, fine motor
dysfunction, poor eye-hand coordination,
hyperactivity, distractibility, short attention span, speech delays.

Fragile X Syndrome Hereditary form of intellectual disability, 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
intellectual disability in males. Associated physical features: prominent jaw, large ears, large testes, ADHD, autism,
moderate to severe intellectual disability (males) (less for females), and mild connective tissue abnormalities. Cause: defect in X chromosome. Inheritance: X-linked
. Incidence 1/2,000 male births, 1/4000 female births. Associated complications: pervasive developmental disorder, communication disorder, behavior
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

Phenylketonuria (PKU) An inborn error of amino acid metabolism without acute symptoms; intellectual disability, 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
intellectual disability
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,
(particularly in the neck region), hypogonadism with cryptorchidism, small hands and feet, hypopigmentation, mild to moderate intellectual disability,
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 is rare, since the placenta does not exchange blood,
but deliver nutrients and take away waste. However, things happen, and just one drop of baby blood causes the mother's blood to build up antibodies. This predisposes
subsequent Rh + babies to
kernicterus (intellectual disability, choreoathetoid cerebral palsy, staining of secondary teeth, upward gaze paralysis, high- frequency
hearing loss; spastic quadriplegia, deafness, severe intellectual disability, 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,
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 intellectual disability. 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 Toxoplasmosis, Syphilis, Rubella, Cytomegalovirus (CMV), and Herpesvirus.

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, intellectual disability, 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
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,
intellectual disability, 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,
intellectual disability. 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
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

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 intellectual disability. XXXXX
is associated with severe intellectual disability 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.

There is one (that I have heard of so far) incidence where a boy has
XX -- de la Chapelle syndrome or XX male syndrome. Look it up! Most interesting. You
can look here: