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 chromosomal 50% of spontanous abortion are chromosomal abnormal Mostly triploidy. 45 XO, trisomy 16 98% of fetus with turner abort Generally 6/1000 the incidence of chromosomal abnormalities

When to suspect it Unexplained infertility/ balanced translocation Multiple abortion >2 Prior case of defective baby

When to suspect it…continue Presence 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 features Hypotonia without weakness Clinodactaly 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 GI Hypothyriodism Transient leukemoid reaction Alzheimer’s disease up to 25% over 40 y/o Early death relate to cardiac dysfunction

Trisomy 18 Incidence 1/8000 Overlaps with trisomy 13 Sever Mental retardation >90% dead in 1st year

Trisomy 18 Small face with prominant occiput Small sternum and pelvis Flexion deformity of the finger VSD and horseshoe kidney

triploidy Complete extra set of chromosomes Mostly miscarriages Fetal wastage skeleton more than cephalic, 2% survive to be recognized Large hydatidiform placenta VSD, ASD, Syndactaly Genital and CNS abnormalities

Trisomy 13 Sever developmetal retardation Incidence 1/20000 90% dead in the 1st year

Trisomy 13 Midline brain defect Malformed ear Microophalmos and coloboma Scalp defect

Turner syndrome Most common abnormality in early abortion Female, short stature, primary amenorrhea, sterility, spares hair and underdeveloped breast Neonatal: wide spaced nipple, lymphedema , shield chest, Coarctation of the aorta

Continue turner syndrome Normal IQ scale with difficulty in spatial orientation such as map Present with short stature or delay sex maturation Hormonal therapy

continue Mosaisim (15%), remove gonads Recurrent risk is 1-2% Noonan syndrom AD, fresh mutation Pulmonary stenosis, nl stature, microceph, mental retardation

Klinefelter syndrome 20% of aspermic adult male (blocked spermatogenesis 47 XXY in 80% and mosaic in 20% IQ is 98 (normal) with mild decrease in verbal IQ Scoliosis, decrease libido may improve with testesterone, gynecomastia

Fragile X Syndrome Moderate to sever mental retardation Speech delay, short attention, hyperactivity Poor motor coordination and mouthing objects Poor socialization, temper tantrum Mood disorder (bipolar), schizophrenia

Fragile X syndrome Long protruding ears Long face and prominent jaw Flattened nasal bridge High arch palate Macroorchidism Genetic is complex, 80% penetration in male and 30% penetration in female

Genetic imprinting Means: 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