Chromosomal abnormalities

Mohammad Khassawneh

Assistant Professor of Pediatrics

introduction Normal human cells contain 23 pairs of

chromosomes This includes one pair of sex chromosome XX

or XY During cell division we can identify

chromosomes Lymphocytes incubated for 2-3 days or

uncultured bone marrow in 4-24 hours

continue Haploid: set of 23 chromosomes Diploid: normal number of 46 chromosomes Aneuploidy: less than an even multiple of 23

usually is 45 or 47 and rarely 48,49 Triploidy: 69 chromosomes Mosaicism Abnormal in deletion and

translocation(balanced and unbalanced)Balanced

Incidence The earlier the abortion the more likely

to be chromosomal50% of spontanous abortion are

chromosomal abnormalMostly triploidy. 45 XO, trisomy 1698% of fetus with turner abortGenerally 6/1000 the incidence of

chromosomal abnormalities

When to suspect it

Unexplained infertility/ balanced translocation

Multiple abortion >2Prior case of defective baby

When to suspect it…continuePresence of congenital anomalies

45% have minor single anomalies 9% 3 minor anomalies 1.5% HAVE major anomaly

2 or more major anomalies may represent genetic syndrome or chromosomal abnormalities(10%).

Down Syndrome Incidence 1/700 2/3 of down fetus spontaneously abort Clinical diagnosis depend on gestalt Trisomy 21 in 94% of cases with extra

chromosome from mother mostly(95%) Risk correlate with maternal age

<25 y/o 1/1600 >40 y/0 1/80

2% are mosaic

Other Clinical featuresHypotonia without weaknessClinodactaly protruded tongue,small

ears,brachycephaly,small up turned nose, depressed nasal bridge.

Mental retardation, socially do better with good environment (Happy children)

Clinical issues

Cardiac and GIHypothyriodismTransient leukemoid reaction Alzheimer’s disease up to 25% over 40

y/oEarly death relate to cardiac dysfunction

Trisomy 18

Incidence 1/8000Overlaps with trisomy 13Sever Mental retardation >90% dead in 1st year

Trisomy 18

Small face with prominant occiputSmall sternum and pelvisFlexion deformity of the fingerVSD and horseshoe kidney

triploidyComplete extra set of chromosomesMostly miscarriagesFetal wastage skeleton more than

cephalic, 2% survive to be recognizedLarge hydatidiform placentaVSD, ASD, SyndactalyGenital and CNS abnormalities

Trisomy 13

Sever developmetal retardation Incidence 1/2000090% dead in the 1st year

Trisomy 13

Midline brain defectMalformed earMicroophalmos and colobomaScalp defect

Turner syndromeMost common abnormality in early

abortionFemale, short stature, primary

amenorrhea, sterility, spares hair and underdeveloped breast

Neonatal: wide spaced nipple, lymphedema , shield chest,

Coarctation of the aorta

Continue turner syndromeNormal IQ scale with difficulty in spatial

orientation such as map Present with short stature or delay sex

maturationHormonal therapy

continue

Mosaisim (15%), remove gonadsRecurrent risk is 1-2%Noonan syndrom AD, fresh mutationPulmonary stenosis, nl stature,

microceph, mental retardation

Klinefelter syndrome20% of aspermic adult male (blocked

spermatogenesis 47 XXY in 80% and mosaic in 20% IQ is 98 (normal) with mild decrease in

verbal IQScoliosis, decrease libido may improve

with testesterone, gynecomastia

Fragile X SyndromeModerate to sever mental retardationSpeech delay, short attention,

hyperactivityPoor motor coordination and mouthing

objectsPoor socialization, temper tantrumMood disorder (bipolar), schizophrenia

Fragile X syndromeLong protruding earsLong face and prominent jawFlattened nasal bridgeHigh arch palateMacroorchidismGenetic is complex, 80% penetration in

male and 30% penetration in female

Genetic imprintingMeans: as genomes pass through

miosis it is normal for part of it to change.

During miosis inactive X chromosome become active and changes on fragiloe X gene (imprinting) make it malignant

Angelman syndrome Sever mental retardation Inappropriate laughter Decrease pigmentation of choroid or iris (pale

blue eyes) Ataxia and jerky eye movement Sever speech proplem Deletion of b15q11q13, maternal in origin Paternal uniparental disomy

Prader-willi syndrome (A fat red faced boy in state of somnolency)

Charles Diickens Early hypotonia Obesity Short stature as adult Almond shaped blue eyes Mental retardation (mild to moderate) Narrow hands

Chromosomal linked disorder Smith Lemli opitz syndrome

Low cholesterol High 7 dehydrocholesterol Like trsomy 18

CHARGE Coloboma Heart Atresia of choanae Retarded Genitalia hypoplasia Ear anomalies

VATER