Chromosomal Disorders

Definitions
• Gene: smallest unit of a single characteristic
• Chromosome: structural elements in the cell
nucleus that carry the genes and convey
genetic information
• Each cell (except RBO) contain all of the
chromosomes from both parents in the nucleus
• 23 pairs of chromosomes come from each parent
• Autosome: one of the 22 pairs of chromosomes
that is not responsible for determining the sex of
the child
• Sex Chromosome: X and Y chromosomes
responsible for sex determination
 Chromosomal Defects
• Abnormal Number
• Monosomy: one less than the diploid number (45)
• Trisomy: one more than the diploid number (47)
• Mosaicism: some cells have the correct
number of chromosomes and some have more
or less than the correct number of
chromosomes
• Abnormal Structure
• Deletion: loss of a chromosomal segment
• Translocation: the occurrence of a chromosomal
segment at an abnormal site either on another
chromosome or in the wrong position on the same
chromosome
 Prenatal Diagnosis
• Maternal Serum Alpha-fetoprotein
(MSAFP)
• Done at 16 – 18 wks gestation
• High MSAFP: incorrect dates; multiple
gestation; neural tube defects,
abdominal wall defects; renal
anomalies; esophageal or intestinal
obstructions
• Low MSAFP: incorrect dates;
chromosomal defect (esp. Trisomy 21)
• Ultrasound
• Amniocentesis
• Usually done at 16 – 18 wks gestation
• Fluid analysis may require up to 2-3 wks
• Can usually determine: fetal sex,
metabolic disorders, chromosomal
abnormalities
• Chorionic Villus Sampling (CVS)
• Usually done at 8 – 10 wks gestation
• Fetal cell analysis usually takes 24 – 48
hours
 Newborn Care
• History
• Family History: any similar relatives,
frequency of spontaneous abortions
• Prenatal History: fetal activity, maternal
exposures, uterine malformations
 Newborn Assessment
• Face: configuration, spacing of feature,
location of features
• Head: size and shape of skull, fontanel
• Eyes: structure, location, color of iris
• Ears: low set or correct location, skin tags
• Nose: number of nares, location, flattened
bridge
• Oral: size and shape of tongue, mouth, jaw
• Neck: webbing, extra folds
• Hands & Feet: broad, square, polydactyly,
abnormal creasures, contractures, overriding
fingers or toes
 Family Support
• Crisis
• Grief – loss of “perfect child”
• Genetic counseling
• Identify the normal
 Trisomy 21
• a.k.a. Down’s Syndrome
• Caused by an extra chromosome 21

Normal Karyotype Trisomy 21 ( 47,XY,+21)

 Trisomy 21
• Incidence
• 1 : 650 – 1000 live births, parental age related
• 75 % abort spontaneously
• Sex ratio: 3 males / 2 females
• Most common autosomal chromosomal disorder
causing mental retardation
• Risk Factors
• maternal age
• Parental carrier of translocation
• Prenatal Testing
• Triple screen (alpha-fetal protein decreased, estriol
decreased, beta-HCG increased)
• If positive, amnio or CVS may be indicated
 Clinical Presentation
•Size: small, 20% are •Tongue: protrudes,
premature tongue thrusting
•Skull: short and round •Skin loose around
with a flat occiput, lateral and dorsal
separated sutures aspects of neck
•Eyes: slant upward and •Hands: fingers are
outward short, hands are square,
•Prominent epicanthal thumbs are low set,
fold separated more than
•Moon-shaped face usual from second
•Brushfield’s spots finger, 5th finger is short
•Cheeks: red and curves inward,
•Palate: narrow and short single/bilateral simean
crease
•Nose: short with flat
bridge •Ears: low-set,
posteriorly rotated ears
 Clinical Presentation
•Umbilicus: herniated •Velvety, loose
•Feet: wide space adhering mottled
between great toe and 2nd skin in infancy,
toe, deep crease
coarse skin in
between great toe and
the 2nd toe, flat feet adolescence
•Heart: VSD •Mouth frequently
•Duodenal atresia open/frequently open
•Muscular hypotonia mouth
•Retarded psychomotor •Visual and/or
development hearing impairment
•Hyperlaxity of
ligaments
 Prognosis
• Congestive heart failure d/t CHD
• Upper respiratory tract infections
• Developmentally delayed
• Mildly to severely mentally retarded:
IQ ranges from 25 – 70
• Increased risk for thyroid problems
and leukemia
 Trisomy 18
• a.k.a. Edward’s Syndrome, Trisomy
E, Trisomy 16 – 18
• Caused by an extra chromosome 18

Normal Karyotype Edward’s Syndrome (47,XY, +18)

 Trisomy 18
• Incidence
• 1 : 6000 – 8000 live births
• F > M (4 : 1)
• Most die in embryonic or fetal life
• Risk factors
• Increased paternal and maternal age
• Prenatal screening
• Good indicator is if in maternal serum during
mid trimester have low human chorionic
gonadotrophin and low unconjugated estriol
• Ultrasound
• If anomalies seen, amnio or CVS may be
indicated
 3 Types of Trisomy 18
• Full Form
• Every cell in the body has 3 chromosome
18 instead of 2
• Severe form
• Mosaic Form
• Some cells have 3 chromosome 18 and
others have 2
• Less severe form
• Partial Form
• In some cells there may be an extra copy of
part of chromosome 18
• Severity dependent on anomalies
 Clinical Presentation
•Prenatal hx: feeble fetal •Mouth: micrognathia,
activity, microstomia, cleft lip,
cleft palate
polyhydramnios, small
•Mental retardation
placenta, single
umbilical artery •Heart: VSD, PDA, ASD
•Feet: rocker bottom, big
•Post-dates toe shortened and
•SGA dorsiflexed, clubfeet
•Weight: low birth •Crossed legs
weight in term infant •Diastasis recti
•Weak cry •Pectus carinatum
•Response to sound •GU defects: horseshoe
kidneys, hydronephrosis,
decreased polycystic kidneys
•Ears: low set and/or
abnormal shape
 Clinical Presentation
•Hands: clenched and •Head: abnormally
with flexed fingers
(usually where index prominent occiput,
finger overlaps 3rd and 4th microcephaly
fingers),flexion
contraction of the two •Hernias: umbilical,
middle digits, inguinal
underdeveloped or
absent thumb, simian •Redundant skin
crease, arches on seven folds esp. over the
or more fingers, nails back of the neck
underdeveloped
•Syndactyly •Males:
•Eyes: ptosis of one or cryptorchidism
both eyelids, epicanthal
folds
 Prognosis
• 20 – 30% die during the first month
• 90% die by age one
• 1% chance of surviving to 10 yrs
• High mortality rate is caused by congenital heart
malformations, gastrointestinal and genitourinary
anomalies, feeding difficulties, and associated
central nervous system defects that produce central
apnea.
• Although they function with severe handicaps, all
older children with Trisomy 18 smile, laugh, interact,
relate to their families, and achieve some
psychomotor maturation.
• Mosaic cases may show milder phenotypic
expression and prolonged survival.
 Care Management
• No treatment beyond supportive care
• NG or GT feedings
• Orthopedic management
• Cardiac management
• Genetic counseling
• Parental support
• Apnea monitoring / O2 if needed
 Trisomy 13
• a.k.a. Patau’s Syndrome, 13+
Syndrome, 13 – 15 D Syndrome,
Trisomy Syndrome
• Caused by an extra chromosome 13

Normal Karyotype Trisomy 13 (47,XX,+13)

 Trisomy 13
• Incidence
• 1 : 5000 live births
• Male = Female
• Risk Factors
• Increases with maternal and paternal age
• Increases with increased parity
• Parental carrier of balanced translocation
• Prenatal Screening
• Ultrasound
• If anomalies seen, amnio or CVS may be
indicated
 Clinical Presentation
•Severe mental and
psychomotor retardation
•Ears: malformed, low-set
•Hands: flexion deformities;
polydactyly, simian crease,
clenched hands
•Heart: VSD, PDA, ASD,
rotational anomalies
(dextrocardia)
•Eyes: microphthalmos,
colobomas of iris,
cataracts, retinal dysplasia,
close set (may fuse into
one)
•Nose: broad and flattened
•Mouth: cleft lip and palate
•Hernias: umbilical hernia,
inguinal hernia
•Kidneys: polycystic
•Skin: cutaneous
hemangiomas
•Head: dermal sinus on
scalp, microcephaly
•Brain: gross defects,
grand mal seizures,
myoclonic jerks, seizures,
holoprosencephaly
 Clinical Presentation
•Skin loose around •Mouth: cleft lip, cleft
lateral and dorsal palate
aspects of neck
•Spine:
•Single umbilical artery meningomyelocele
•Apnea
•Feet: rocker bottom
•Genitalia
•Low-birth weight
•Female:
bicornate/septate •Omphalocele
uterus
•GI XR or US may
•Male: cryptorchidism
reveal abnormal
rotation of internal
organs
 Prognosis
• 82% die within the first month
• 5 - 10% survive the first year
• Survival to adulthood rare
• Common disorders if survive beyond 1
month of age
• Severe mental retardation
• Feeding disabilities
• GE reflux
• Slow post natal growth
• Apnea
• Kidney defects
• Seizures
• Developmental disabilities
• Scoliosis
 Care Management
• No treatment beyond supportive care
• Parental support
 Turner’s Syndrome
• a.k.a. TS, Monosomy X, Gonadal
Dysgenesis, Bonnevie-Ullrich Syndrome,
XO Syndrome
• Is the absence of one set of genes from
the short arm of one X chromosome

Normal Karyotype Turner’s Syndrome (45,X)

 Turner’s Syndrome
• Incidence
• 1 : 2000-3000 live-born females
• Females only affected
• 98% of pregnancies with TS spontaneously abort
• 10% of pregnancies that spontaneously abort have TS
• Risk Factors
• Increased paternal age
• Mother with mosaic or deletional Turner’s Syndrome
• SHOX gene association
• SHOX gene provides instructions for making a protein
that regulates activity of other genes
 Clinical Presentation
•Short stature; mean •Heart: coarctation of
birth weight 2.9 kg; the aorta, aortic vavular
average height: 4’7” stenosis, bicuspid aortic
valve, aortic dissection
•Webbed neck
•Eye: ptosis, strabismus,
•Low posterior hairline amblyopia, cataracts,
•Micrognathia epicanthal folds, dry
•Ears: low-set, eyes, red-green color
blindness
sometimes malformed,
•Congenital hip
prone to otitis media
dislocation
•Widely spaced •Abnormal growth
hypoplastic nipples on a patterns
shield-shaped chest •Congenital
•Increased carrying lymphedema of hands
angle at the elbow and feet
 Clinical Presentation
•Absent or retarded •Gonadal dysplasia
development of •Horseshoe kidney
secondary sexual •Unilateral renal
characteristics that agenesis
normally appear at
•Intelligence: not at
puberty
risk for mental
•Absent
retardation, better
menstruation verbal then
•Absence of normal visuospatial abilities
vaginal moisture •Broad nasal bridge
•infertility
 Prognosis
• Females are basically normal despite failure of
sexual development
• At risk for
• Middle ear infections
• Scoliosis
• Arthritis
• Cataracts
• Hashimoto’s thyroiditis
• Kidney abnormalities
• High blood pressure
• Obesity
• Diabetes mellitus
• Osteoporosis
• Keloid formation
 Care Management
• Early
• Supportive care
• Surgery to correct treatable defects
• Late
• Growth hormone therapy
• Estrogen replacement therapy
• Counseling and psychiatric support
• 2 – 5% have some ovarian function and can
menstruate and become pregnant
• Others can have children using donor eggs and
in-vitro fertilization
 VATER Association
• VATER = Vertebral anomalies
Anal atresia
Tracheo-Esophageal fistula,
Radial and renal dysplasia
• Incidence
• Unknown
• Etiology
• Unknown
 Clinical Presentation
• Three or more of the following
defects must be present:
• Vertebral anomalies
• Anal atresia with or without fistula
• TEF with EA
• Radial dysplasia, including thumb or
radial hypoplasia, polydactyly, and
syndactyly
• Renal anomaly
• Single umbilical artery
• Prognosis
• FTT
• Possibility of normal life after slow
mental development during infancy
• Care Management
• Supportive care
• Surgery: surgical correction of
anomalies