By Momina Shehzadi | BS Zoology Graduate, Pakistan In this article, we will learn Fungi - Morphology, Reproduction, Physiology and Importance - in simple words with diagram. This topic is very important for BS Zoology and Microbiology students. Fungi are found everywhere around us. They are present in soil, in water, in air, on dead plants, on dead animals, on our food, on our skin and even inside our body. When bread becomes old, green or black spots appear on it. These spots are fungi. When we see mushroom growing after rain, that is also a fungus. When yeast is used to make bread soft, that is also a fungus. Fungi are very different from bacteria and plants. They are eukaryotic organisms. It means their cells have a true nucleus and other membrane bound organelles. They do not have chlorophyll, so they cannot make their own food like plants. They get their food from other living or dead things. That is why they are called heterotrophic organisms. The study of fungi is called mycolog...
By Momina Shehzadi | BS Zoology Graduate, Pakistan
In this article, we will learn about 6 Human Genetic Syndromes - Down, Turner, Klinefelter, Edwards, Jacobs and Patau - in simple words with symptoms, genetics and counseling. This topic is very important for BS Zoology, Genetics, and MBBS students.
COMPLETE GUIDE TO 6 HUMAN GENETIC SYNDROMES
Human chromosomal syndromes occur due to an abnormal number of chromosomes. Normal human karyotype is 46,XX (female) or 46,XY (male). Any addition or deletion leads to a syndrome. These are divided into autosomal trisomies (Down, Edwards, Patau) and sex chromosomal aneuploidies (Turner, Klinefelter, Jacobs). Here is the detailed study of all 6.
1. Down's Syndrome
(Trisomy 21)
This is the most common autosomal trisomy and the most common genetic cause of intellectual disability. Incidence is 1 in 700-800 live births worldwide.
A) Symptoms
. Facial features include flat facial profile,
(mongoloid slant),
epicanthic folds, Brushfield spots on the iris, small low-set ears, and a small mouth with a large protruding tongue.
The head is brachycephalic with a flat occiput.
Hand features are diagnostic: single palmar crease (Simian crease), clinodactyly of 5th finger (inward bending), Body features include short stature (mean adult male 157 cm, female 144 cm), hypotonia (floppy baby), and hyperflexibility of joints. Intellectual disability is mild to moderate with IQ 40-60. Systemic complications are critical: 40-50% have congenital heart defects, most commonly Atrioventricular Septal Defect (AVSD), followed by VSD. Others include duodenal atresia (double bubble sign), hypothyroidism in 20-30%, hearing loss in 75%, cataract, and increased risk of leukemia .
B) Genetics:
Karyotype is 47 chromosomes.
Three types exist: 95% Free Trisomy 47,XX,+21 due to nondisjunction and translocations .
C) to Molecular basis:
It is a gene dosage effect. Chromosome 21 is the smallest autosome with ∼300 genes. 1.5 times over expression cause disease. The Down Syndrome Critical Region (DSCR) at 21q22 is most important.
D) Pattern of Inheritance:
Mostly sporadic, not Mendelian. Free trisomy is a random meiotic error. 90% of nondisjunction occurs in maternal meiosis I, especially in old oocytes where cohesion proteins degrade. Recurrence risk after one affected child with normal parental karyotypes is 1% plus maternal age risk, due to gonadal mosaicism. Translocation form is heritable. A balanced carrier parent has 45 chromosomes. If mother is t(14;21) carrier, risk of Down child is 10-15%. If father is carrier, risk is 3-5% because abnormal sperms are selected against. If carrier is t(21;21), risk is 100% - no normal child is possible because all gametes have disomy 21.
E) Genetic counselling:
This is mandatory.
Step 1: Take detailed pedigree and maternal age. Step 2: Non-directive counselling, remove guilt, explain nature.
Step 3: Do parental karyotyping from blood to rule out translocation.
Step 4: For next pregnancy, offer prenatal diagnosis - NIPT (cell-free fetal DNA) at 10 weeks as screening, and CVS at 11-13 weeks or Amniocentesis at 15-18 weeks for confirmation.
Step 5: Postnatal management - echocardiography ,TSH, hearing and vision screening, early physiotherapy, speech therapy, and family support through Pakistan Down Syndrome Association. Life expectancy now is up to 60 years with cardiac surgery.
2. Turner Syndrome: Monosomy X
It is the only viable monosomy in humans, affecting only females. Incidence 1 in 2500 female live births. 99% of 45,X conceptions abort spontaneously, only 1% survive.
A) Symptoms:
Cardinal feature is short stature, average adult height 143 cm without growth hormone treatment. Gonadal dysgenesis - streak ovaries made of fibrous tissue, leading to primary amenorrhea, infertility, and lack of secondary sexual characteristics. Neck shows webbed neck (pterygium colli) with low posterior hairline. Chest is broad shield-like with widely spaced nipples. Lymphedema of hands and feet at birth is diagnostic.
B) Genetics:
Karyotype 45,X. About 50% are pure 45,X due to paternal sex chromosome loss or nondisjunction.
C) Molecular Basis
Loss of genes on short arm of X chromosome .
D) Pattern of Inheritance:
Sporadic, not inherited. It is due to meiotic nondisjunction or anaphase lag. About 70-80% of cases, the single X is maternal, meaning paternal X or Y was lost. Recurrence risk is not increased for next pregnancy if parents are normal - it is <1%. It is not related to maternal age. No increased risk for siblings.
E) Genetic Counselling:
Reassure parents that recurrence is rare. Prenatal diagnosis by CVS/amniocentesis can detect it. Postnatal care includes growth hormone therapy starting at age 2-3 years to improve height by 7-10 cm. Estrogen replacement at age 12-13 for puberty. Cardiac MRI mandatory to rule out coarctation. Regular thyroid (hypothyroidism in 25%), hearing, and renal ultrasound. Fertility options: donor egg IVF. Psychological support for short stature and infertility is important. Mosaic cases may have spontaneous puberty and even fertility.
3. Klinefelter Syndrome:(47XXY)
It is the most common sex chromosome aneuploidy in males, 1 in 1000 male births, but 70% remain undiagnosed.
A) Symptoms:
Tall stature with long limbs, arm span more than height due to extra X affecting long bone growth. After puberty, hypogonadism develops: small firm testes, azoospermia, infertility, low testosterone leading to gynecomastia (breast enlargement in 50%), decreased facial and pubic hair. Learning difficulties are common: language delay, reading disability, and IQ 10-15 points lower than siblings. Behavioral issues like shyness and immaturity. Increased risk of osteoporosis, diabetes, breast cancer (20 times more than normal male), and autoimmune diseases.
B) Genetics:
Karyotype 47,XXY in 80% cases. 15% mosaic 46,XY/47,XXY with milder phenotype and possible fertility. 5% variants 48,XXXY, 49,XXXXY with more severe intellectual disability and malformations.
C) Molecular Basis:
Due to extra X chromosome. In normal male, one X is active. In XXY ,one X undergoes inactivation, but pseudoautosomal regions escape, causing overdosage.
D) Pattern of Inheritance:
Sporadic due to nondisjunction in either parent. 50% of nondisjunction is maternal (XX egg) and 50% paternal (XY sperm). Slightly increased with advanced maternal age.
E) Genetic Counselling:
Most cases diagnosed in infertility clinics. Counselling should explain that it is random, not parent's fault. Prenatal diagnosis available. Postnatal management: testosterone replacement from puberty (11-12 years) to improve virilization, muscle mass, and prevent osteoporosis. Early speech therapy for language delay. Educational support. Fertility - 50% have sperm in testes retrievable by micro-TESE and ICSI possible. Psychological counselling for gynecomastia and infertility. Breast examination for malignancy.
4) Edwards Syndrome
(Trisomy 18) - 47,XX,+18 or 47,XY,+18
Second most common autosomal trisomy, incidence 1 in 5000 live births, but more common in conception as most abort.
A) Symptoms:
Low birth weight and severe growth retardation. Characteristic clenched fist with overlapping fingers - index finger over middle finger and 5th finger over 4th finger. Rocker-bottom feet with prominent heel. Micrognathia (small jaw), low-set malformed ears, cleft lip/palate, short sternum and developmental delay.
B) Genetics:
Full trisomy 18 in 94%. Mosaic 5%, milder and may survive longer. Translocation <1%.
C) Molecular Basis:
Chromosome 18 has ∼300 genes. Overexpression disturbs development. Genes like ROCK1, TGIF cause heart and brain defects. Mechanism similar to Down but chromosome 18 genes are more critical for survival, hence lethality is high.
D) Pattern of Inheritance:
Sporadic, complete nondisjunction. Strong maternal age effect, mean maternal age 32 years. Recurrence risk 1% plus maternal age risk. Translocation form is rare but heritable like Down, with high recurrence.
E) Genetic Counselling:
Prognosis must be explained honestly. Most parents opt for palliative care due to high lethality. Recurrence risk counselling and prenatal diagnosis for next pregnancy with amniocentesis. Detailed ultrasound can show clenched hands, heart defects, and growth restriction. If mosaic, prognosis is variable and counselling is difficult. Supportive care includes cardiac surgery in selected mosaic cases.
5) Jacob's Syndrome (47,XYY)
Incidence 1 in 1000 male births, most undiagnosed as phenotype is mild.
A) Symptoms:
Tall stature, mean adult height 6 cm taller than average, above average growth velocity from childhood. Normal genitalia, normal testosterone, fertile - most are fathers without knowing karyotype. Acne in adolescence may be severe. Learning difficulties in 50%, especially reading delay, and speech delay. IQ slightly lower (10-15 points) but usually in normal range.
B) Genetics:
Karyotype 47,XYY
Mosaic 46,XY/47,XYY
Due to paternal meiosis II nondisjunction producing YY sperm.
C) Molecular Basis:
Extra Y chromosome.
Y chromosome is gene-poor, so extra copy is better tolerated than autosome.
D) Pattern of Inheritance:
Sporadic, due to paternal nondisjunction only, as Y comes from father. Not related to parental age. Recurrence risk <1%. Not inherited as males are fertile but could produce XY or YY sperm; risk of aneuploid offspring is slightly higher but low.
E) Genetic Counselling:
Many XYY males live normal life. No need for testosterone therapy. Early educational intervention for speech and reading. Psychological support for behavioral issues. Prenatal counselling - if detected on amniocentesis for other reason, most families continue pregnancy as outcome is good. This is important to explain to avoid unnecessary termination.
6. Patau Syndrome:
(Trisomy 13) - 47,XX,+13 or 47,XY,+13
Incidence 1 in 10,000-12,000 live births. Most severe viable autosomal trisomy.
A) Symptoms:
Severe midline defects. Microcephaly, holoprosencephaly (brain not divided), severe cleft lip and bilateral cleft palate, microphthalmia or anophthalmia (small or absent eyes), polydactyly (extra fingers/toes, usually postaxial), scalp defects (cutis aplasia), rocker-bottom feet. Heart defects in 80%: VSD, ASD, PDA. Omphalocele, polycystic kidneys. Severe intellectual disability and seizures. Median survival 7-10 days, only 5% survive 6 months. Mosaic cases survive longer.
B) Genetics:
Full trisomy 13 in 75%, Robertsonian translocation t(13;14) in 20%, mosaic 5%.
C) Molecular Basis:
Chromosome 13 has genes like ZIC2 for brain development. Overdosage causes holoprosencephaly. The 13q region is critical. Similar gene dosage imbalance mechanism.
D) Pattern of Inheritance:
Mostly sporadic nondisjunction with maternal age effect. Translocation form t(13;14) can be balanced carrier in parent with 45 chromosomes. Carrier risk: if mother carrier, risk of Patau child is 10-15%, if father carrier 3-5%. Like Down syndrome, 100% recurrence if t(13;13) which is very rare.
E) Genetic counselling
Similar to Edwards - poor prognosis, discuss palliative care. Cleft, polydactyly and heart defect. Karyotype of parents mandatory to rule out translocation as recurrence is high.
Conclusion
All six syndromes are chromosomal aneuploidies diagnosed by karyotyping, now also by NIPT and microarray. Early genetic counselling helps families understand recurrence and management. While Turner, Klinefelter and Jacobs have good life expectancy, Down has moderate, and Edwards and Patau have very poor survival. Modern management is multidisciplinary and focuses on quality of life.
FAQs
Q1: What is normal human karyotype?
Ans: Normal human karyotype is 46,XX for female and 46,XY for male. Any extra or missing chromosome causes a syndrome.
Q2: Which is the most common autosomal trisomy?
Ans: Down Syndrome - Trisomy 21 is the most common. Incidence is 1 in 700-800 live births. It causes intellectual disability and heart defects.
Q3: Which syndrome affects only females?
Ans: Turner Syndrome - 45,X affects only females. It causes short stature, webbed neck, and primary amenorrhea due to streak ovaries.
Q4: Which syndrome has the worst survival?
Ans: Patau Syndrome - Trisomy 13 has the worst survival. Median survival is only 7-10 days. Edwards Syndrome - Trisomy 18 also has poor survival.
Written by Momina Shehzadi, BS Zoology Graduate from Pakistan.
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