Trisomy 13- Patau syndrome Mental deficiency; Severe central nervous system malformations; Severe central nervous system malformations; Sloping forehead; malformed ears, scalp defects;

Microphthalmia; Bilateral cleft lip and/or palate; Polydactyly; posterior prominence of the heels.

Trisomy 18- Edwards syndrome Mental deficiency; growth retardation; growth retardation; prominent occiput; short sternum; ventricular septal defect; micrognathia; low-set malformed ears, flexed digits, hypoplastic nails; rocker-bottom feet.

Turner syndrome- XO

Klinefelter syndrome- XXY trisomy Small testes, hyalinization of seminiferous tubules; aspermatogenesis; Often tall with disproportionately long lower limbs. Intelligence is less than in normal siblings. Approximately 40% of these males have gynecomastia

Cri du chat syndrome- terminal deletion chromosome 5

Fragile X syndrome 1 in 1500 male births may account for much of the excess of males in the mentally retarded population

Achondroplasia

TERATOGENS Any agent that can produce a congenital anomaly or oncrease the incidence an anomaly in the population

TERATOLOGY Study of causes, mechanisms, and patterns of abnormal development Basic concept is that certain stages of embryonic development are more vulnerable to disruption than others

Organs and parts of embryo are most sensitive to teratogenic agents during periods of rapid differentiation Possible mechanisms of action include alteration in intracellular matrix and fetal environment Teratogens probably cause disruption of gene activity at any critical stage

Principles of teratogenesis Critical periods of development Dosage of drug or chemical Genetic constitution of the embryo

DRUGS

THALIDOMIDE

alcohol

Phenytoin

Viruses Rubella

Toxoplasma infection

Female hormones Masculinisation of female external genitalia due to maternal use of drug during pregnancy

STATISTICS 50% of all human conceptions are lost either before implantation or soon afterwards 15% of recognized pregnancies end in spontaneous abortion before 12 weeks gestation 80-85% of aborted embryos have gross structural abnormalities, varying from complete absence of embryo in gestational sac [blighted ovum] to a very distorted body shape, or a specified abnormality in a single body system

STATISTICS……… 20-30% of all perinatal deaths occur as a result of a serious structural abnormality In 80% of these cases, genetic factors can be implicated, with a recurrence rate of 1% or more 2-3% of all newborns have at least one major abnormality 10% newborns have minor abnormalities

STATISTICS…………… Anomalies can be single or multiple, and of minor or major clinical significance 14% of newborns have single minor anomaly Minor anomalies indicate presence of associated major anomalies Presence of a single umbilical artery is associated with cardiovascular or renal anomalies 90% of babies with 3 or more minor anomalies also have 1 or more major defects

STATISTICS……… If 2 or more abnormalities are present in a newborn infant, there is a 10-20% risk of a major malformation 25% of newborn babies with a major malformation die in early infancy- 25% have a subsequent mental physical disability-the remaining 50% have a fair to good outlook after treatment

Causes of congenital anomalies Causes of congenital anomalies

Brief history st well-documented reports of maternal rubella infection as a cause of cataracts, cardiac defects and deafness in the offspring Thalidomide tragedy- thalidomide was widely used as a sedative during Severe limb anomalies were seen in babies born to mothers who took it in 1 st trimester 40% of these babies died in early infancy due to severe cardiac, renal or GI anomalies

Genetic factors 50-60% of spontaneously aborted fetuses have chromosomal abnormalities 1/3 rd of all congenital anomalies are caused by genetic factors Autosomes and/ or sex chromosomes can be affected Persons with chromosome abnormalities have characteristic phenotype- they often look more like other similarly affected persons than their siblings

Abnormal chromosome number Usually as a result of non disjunction of homologous chromosomes or 2 chromatids of a chromosome in mitosis or meiosis This results in trisomy Down syndrome is an example of trisomy affecting autosomes In Klinefelter syndrome trisomy affects sex chromosomes

Abnormal chromosome structure TranslocationDeletion Ring chromosome

A, Reciprocal translocation. B, Terminal deletion. C, Ring chromosome. D, Duplication. E, Paracentric inversion. F, Isochromosome. G, Robertsonian translocation..

Gene mutation (gene defect) 8%of all anomalies Loss or change in function of a gene Most mutations are deleterious and some are lethal Environmental agents such as radiation can accelerate mutation rate Anomalies due to gene mutation are inherited as recessive or dominant traits

Environmental factors Teratogens: agents that can produce a congenital anomaly or increase the incidence of an anomaly Environmental factors may stimulate genetic conditions when two or more children of normal parents are affected Not everything that is familial is “genetic”