Chromosomal Abnormalities and Syndromes

Numerical Chromosomal Abnormalities

• Trisomy of Autosomes: Results in conditions like Down Syndrome (Trisomy 21), Edwards Syndrome (Trisomy 18), and Patau Syndrome (Trisomy 13).
• Trisomy of Sex Chromosomes:
  • Klinefelter Syndrome (47, XXY): A genetic condition in males caused by an extra X chromosome. Often undiagnosed until adulthood. Cells contain 47 chromosomes with XXY sex chromosomal pattern. Key features include sterility, testicular atrophy, and sometimes gynecomastia.
  • Triple X Syndrome (47, XXX): Caused by an extra X chromosome, occurring in oocytes or sperm.
  • Turner Syndrome (45, XO): The only monosomy compatible with life, but 98% of affected fetuses are aborted. Survivors are female in appearance with key characteristics like absence of ovaries, short stature, webbed neck, lymphedema, and a broad chest.

Microdeletion Syndromes

• Angelman Syndrome: Caused by microdeletion on the maternal chromosome 15. Symptoms include mental retardation (intellectual disability), difficulty speaking.and often prone to unprovoked laughter.
• Prader-Willi Syndrome: Caused by microdeletion on the paternal chromosome 15. Symptoms include hypotonia (low muscle tone), obesity, mental retardation, and often hypogonadism (underdevelopment of the sex glands).

Fragile X Syndrome

• Cause: Mutation in the FMR1 gene (Fragile X Mental Retardation 1), causing too little or no protein production, essential for proper brain growth. Affects both boys and girls, but boys are more severely impacted.
• Clinical features: Mental retardation, large ears, prominent jaw, and pale blue irises.

Microdeletion Syndromes:

• Cri-du-chat Syndrome: Caused by a partial deletion of the short arm of chromosome 5. Characterized by a distinctive cry (cat-like) and often includes microcephaly, mental retardation, and congenital heart defects.

Microdeletion Syndromes

• General characteristics: Caused by the deletion of a few contiguous genes. The effects depend on whether the deletion occurs on the maternal or paternal chromosome.

Oogenesis

• Definition: Oogenesis is the process producing mature oocytes.
• Timeline: The maturation of oocytes starts before birth.
• Differentiation: Primordial germ cells become oogonia, which then undergo multiple mitotic divisions.
• Arrest in Meiosis: Many oogonia stop dividing, arresting in meiosis I, which leads to primary oocytes.
• Hormonal Control: During puberty, GnRH stimulates the release of FSH and LH which trigger follicular development.
• Follicular Growth: The primary oocytes are surrounded by supporting follicle cells and develop into mature follicles.
• Meiosis II: The mature egg, a secondary oocyte, is ready for release, but the meiosis II process halts if there's no fertilization.
• Fertilization: Completing the meiosis II development if fertilization begins.
• Outcome: Leads to one mature egg (ovum) and some polar bodies, which are smaller nonfunctional cells that are released.

Spermatogenesis

• Definition: Spermatogenesis is the development of mature sperm.
• Process: Begins with the differentiation of primordial germ cells into spermatogonia.
• Stages: Several mitotic divisions and a meiotic process resulting in four functional spermatids in spermatogenesis.
• Spermiogenesis: The development of spermatids into sperm.

Ovulation/Ovarian Cycle

• Timing: During puberty, regular monthly cycles, as known as sexual cycles.
• Hormonal Control: Controlled by Gonadotropin-Releasing Hormone (GnRH), secreted by the hypothalamus.
• Follicular Growth: 15 to 20 primary-stage (preantral) follicular growth, stimulated by FSH, which occurs under the influence of FSH. 
• Mature follicles: Prior to ovulation, the follicles grow significantly and are then called mature vesicular follicles or Graafian follicles.

Zygote Formation

• Formation: The definitive oocyte contains female pronucleus, which involves 23 homologous chromosomes. Sperm containing 23 chromosomes. The sperm tail separates, moving towards cytoplasmic oocyte to combine with the female pronucleus and restore diploid number of chromosomes in zygote formation. 

Cleavage and Morula Formation

• Formation: Zygote divides into the two cells, and cleavage then continues to produce a morula (16 cells).
• Morula Differentiation: The cells in the morula differentiate into outer and inner cell masses.

Blastocyst Formation

• Definition: Blastocele forms within the morula, leading to the blastocyst formation.
• Structure: Consists of inner cell mass(embryoblast) and outer cell mass (trophoblast) forming a blastocyst cavity (blastocele).

Implantation

• Happens after the blastocyst hatches.
• The outer layer, trophoblast, contacts the endometrium, enabling implantation.

Human Chorionic Gonadotropin (hCG)

• Definition: A glycoprotein produced by the syncytiotrophoblast during pregnancy.
• Function: Stimulates progesterone production by the corpus luteum (this supports the pregnancy).
• Detection: This is a factor in pregnancy tests; found in maternal blood from day 8 and can be detected in maternal urine from day 10.

Gestational Trophoblastic Disease (GTD)

• Definition: Malignant tumor of the trophoblast. 
• Potential Precursors: can occur after normal pregnancy, abortion, or hydatidiform mole
• Symptoms: High hCG levels and possible metastasis. 

Gastrulation

• Process: The bilaminar disc, (the epiblast and hypoblast) converts into a trilaminar embryo composed of three germ layers.
• Key Component Formation: A primitive streak becomes apparent, indicating the beginning.

Normal Regression of Primitive Streak

• Significance: The primitive streak becomes less prominent during the 4th week. This cessation is necessary for normal development, as remnants of this streak can result in formation of a sacrococcygeal teratoma in newborns.

Birth Defects Associated with Laterality

• Situs Inversus: A condition in which the positioning of the body's organs is reversed, creating a mirror image arrangement (e.g., reversed heart).

Sensitivity of Third Week

• Teratogenic Insults: The third week of development, specifically the time frame with gastrulation, is incredibly sensitive to teratogenic insults. These are environmental factors (e.g., alcohol) that can harm the developing fetus.

Twin Formation

• Definition:Twins are formed either by the fertilization of two different secondary oocytes (dizygotic or fraternal twins) or by one secondary oocyte fertilized by one sperm only, subsequently splitting into two zygotes leading to identical or monozygotic twins.

Twin Transfusion Syndrome (TTS)

• Cause: In monozygotic twins who share a common placenta, connected vascular blood vessels within the shared placenta allow blood to flow from one twin to the other.
• Result: This leads to an unequal blood supply and differing rates of growth between the two twins. This can cause health issues for the one receiving less blood.

Striated Skeletal Muscles

• Definition: Skeletal muscles attached to bones, responsible for voluntary movements. 
• Migration/Formation: During development, cells from the ventral lateral plate mesoderm migrate to form various skeletal muscle groups (including the abdominal wall, limb, and infrahyoid). 

Limb Defects

• Amelia: Complete absence of one or more extremities.
• Meromelia: Partial absence of an extremity.
• Micromelia: All segments of an extremity are present but extremely short.
• Brachydactyly: Shortened fingers or toes.
• Syndactyly: Fusion of fingers or toes.

Polydactyly

• Definition: Condition where a baby is born with one or more extra fingers or toes.

Limb Defects: Cleft Hand and Foot

• Definition: Involves a cleft or split in the metacarpal/metatarsal bones, along the second and fourth bones with the surrounding soft tissue.
• Characteristics: Metacarpal/metatarsal bones 2 and 4 typically absent. Often also fused metacarpals 4 and 5.

Limb Defect: Arthrogryposis

• Definition: Congenital joint contractures affecting more than one joint.
• Causes: Primarily related to neurological abnormalities, muscular abnormalities, and joint problems.

Amniotic Bands

• Cause: Unclear, but likely due to adhesions between the amnion (the membrane surrounding the fetus) and fetal structures, or tears in the amnion. 
• Result: Can cause constrictions or amputations of limbs or extremities.

Preeclampsia

• Definition: A complication of pregnancy, characterized by high blood pressure and protein in the urine.
• Development: Beginning around 20 weeks of gestation, often suddenly, but can develop until delivery.
• Outcomes: Potentially fatal for both mother and child. Can progress and lead to eclampsia.

This quiz covers numerical chromosomal abnormalities, including various trisomies like Down Syndrome and Klinefelter Syndrome. It also explores microdeletion syndromes, such as Angelman Syndrome. Test your understanding of these genetic conditions and their implications.