Clinical services offered at the Centre of Excellence in Paediatrics & Child Care
At Manipal Hospitals we offer Clinical diagnostics and Genetic counseling for the following indications:
Multiple congenital abnormalities
Congenital abnormalities are caused in the foetus developing in the uterus. Five categories of congenital abnormalities include:
Normal chromosomes carry gene structures from one generation to the next and number 46 - twenty-three are from the father and twenty-three from the mother. When the foetus develops without 46 chromosomes, or when pieces of the chromosomes are missing or duplicated, the baby may be born with serious health issues such as Down syndrome.
Sometimes the chromosomes are normal in number, but one or more of the genes in them are abnormal.
Conditions during pregnancy that can cause abnormalities in the foetus:
If the mother contracts certain illnesses like chicken pox or rubella, or has chronic health issues such as diabetes, hypertension, auto immune diseases like lupus, particularly during the first nine weeks.
Alcohol consumption and certain drugs
Eating raw or uncooked foods.
Certain medications or chemicals that can pollute air, water, and food.
Combination of genetic and environmental problems combined with exposure to certain environmental influences within the womb during critical stages of the pregnancy can cause spina bifida – when the spinal cord doesn’t develop, and cleft lip and palate).
Prenatal onset of growth retardation/ Failure to thrive
Intrauterine growth restriction is where the foetus is smaller than expected for the number of weeks of pregnancy, and can begin at any time in pregnancy. Early-onset is often due to chromosomal abnormalities, maternal disease, or severe problems with the placenta. Late-onset usually after 32 weeks, is usually related to other problems. When there is not enough blood flow through the placenta, the foetus may only receive low amounts of oxygen causing the foetal heart rate to decrease, thus placing the baby at great risk.
Children with dysmorphic features/ syndrome diagnosis
Numerous genetic conditions are evident and diagnosable during the neonatal period because of a specific pattern of clinical features often present on infant physical examination. This chapter reviews several of the more frequently observed genetic dysmorphic conditions neonatal practitioners are most likely to encounter in a foetus include Turner syndrome (TS), CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital and ear abnormality syndrome, and VACTERL (vertebral, anal, cardiac, tracheoesophageal, renal, and limb) association. The genetic dysmorphology evaluation or physical examination of the infant is done from head-to-toe noting facial or body asymmetries, malformations, or deformations.
Developmental/ intellectual disability of unknown causes
Developmental disabilities are a group of conditions caused due to impaired learning, language, or behaviour skills. Intellectual disability (formerly mental retardation) involves problems with intellectual functioning such as learning, problem solving, and adaptive functioning such as communication and independent living. An intellectual disability describes below-average IQ and a lack of skills needed for daily living.
Family history of siblings death of unknown causes
Fatty acid oxidation has been proved as the only group of inherited metabolic disorders responsible for sudden infant death syndrome (SIDS). Despite these disorders being rare it is has been important to identify those cases where an inherited defect is the likely cause or contributes to the cause of death or a near miss death in infancy. In many cases of SIDS there is a history of illness preceeding death and such cases of sudden unexpected death in infancy are important to consider.
Bad obstetric history/ Infertility
A woman is said to have 'bad obstetric history (BOH)' if she has experienced any of the following events on two or more occasions in the past:
Consecutive spontaneous abortions.
Early neonatal deaths.
Intrauterine fetal deaths.
Intrauterine growth retardation.
Congenital anomalies in the fetus.
Cervical cultures should be obtained during the evaluation of infertility.
Empiric antibiotics should be given before invasive testing, such as HSG.
Primary amenorrhea is the failure of menses to occur by age 16 years, in the presence of normal growth and secondary sexual characteristics. If by age 13 menses has not occurred and the onset of puberty, such as breast development, is absent, a workup for primary amenorrhea should start
Genetic or inborn conditions are the most common causes of primary amenorrhea. Amenorrhea may result from disorders of the ovaries, pituitary gland, hypothalamus, or uterus. Intensive exercising, extreme weight loss, physical illness, and stress can all result in amenorrhea.
Primary amenorrhea is the failure to begin menstruation when expected. Age 15 is commonly used as the cutoff for primary amenorrhea
Chromosome instability syndrome
chromosome instability syndromes (CIS) are a group of inherited conditions transmitted in autosomal recessive pattern characterised with both mental and physical development delay generally. They are also with other medical complications in individuals with CIS commonly including different degree of dysmorphics, organs/systems dys-function and high risk of cancer predisposition. ChromosIndividuals with CIS are commonly in childhood and these disorders are often lethal. Diagnosis is complicated usually because the symptoms presented from individuals with CIS may be varied and complex. Advances in molecular level have identified genes responsible for such group diseases/disorders demonstrated that CIS are characterized by the genome instability, defect in DNA repair mechanisms.
Family history of known genetic disorder
Genetic disorders typically involve the inheritance of a particular mutated disease-causing gene, such as sickle cell disease, cystic fibrosis, and Tay-Sachs disease. The mutated gene is passed down through a family, and each generation of children can inherit the gene that causes the disease.
Genetic disorders can be monogenic, multifactoral, or chromosomal.
Positive antenatal screening
he results of a screening test are either 'screen positive' or 'screen negative'. A screen positive result means that the risk is high enough to consider having prenatal diagnosis. It does not mean that the baby is definitely affected. Most of those with screen positive results go on to have normal babies. Similarly, a screen negative result means that there is not a high risk. It does not mean that an affected pregnancy has been completely excluded.
Cancer is the most common human genetic disease. The transition from a normal cell to a malignant cancer is driven by changes to a cell’s DNA, also known as mutations. Some people are born with a gene mutation that they inherited from their mother or father. This damaged gene puts them at higher risk for cancer than most people. When cancer occurs because of an inherited gene mutation, it is referred to as hereditary cancer.
Interpretation of cytogenetics/ Molecular genetics report
Cytogenetics is a field of study that deals with chromosomes and related abnormalities. Chromosome analysis is also known as karyotyping and involves the pairing of homologous chromosomes. Cytogenetic analysis is very crucial in the diagnosis of oncologic and hematologic disorders. Molecular genetics utilizes the mechanisms of DNA technology in order to investigate gene mutations.
Following are the tests performed in Medical Genetics Laboratory
Karyotyping is a type of laboratory test that examines and analyzes chromosomes and their abnormalities such as dividing cells. The pairs of chromosomes are arranged by their size and appearance. The karyotype test helps determine if any chromosomes are missing or damaged.
Karyotyping of the following sample / specimens
Peripheral venous blood
A blood sample is drawn from a vein in your arm to detect any chromosomal abnormalities for the following reasons: If pregnancy screening tests are abnormal; signs of a chromosomal abnormality-associated disorder are present in family members; when a person has leukemia, lymphoma, myeloma, myelodysplasia or another cancer and an acquired chromosome abnormality is suspected.
Prenatal diagnosis during pregnancy- Chorionic villi, amniotic fluid, cord blood
The obstetrician or gynaecologist draws out samples of cord blood, amniotic fluid or chorionic villi from the placental lining to test for potential pregnancy loss. Screening can detect problems such as neural tube defects, chromosome abnormalities, and gene mutations that would lead to genetic disorders and birth defects, such as spina bifida, cleft palate, Downs Syndrome, Tay–Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, and fragile X.
There are two types of bone marrow tests - bone marrow aspiration or biopsy. This is done to identify the Philadelphia chromosome, which is found in 85% of people with chronic myelogenous leukemia (CML). It is also done when leukemia, lymphoma, myeloma, myelodysplasia or another cancer and an acquired chromosome abnormality is suspected.
Product of conception ( abortus)
Specimens of miscarriage tissues, known as products of conception, are tested by fibroblast culture to rule out a chromosome abnormality, which is a likely cause of the abortion.
Fluorescence In- Situ Hydridization ( FISH)
Fluorescent in situ hybridization (FISH) can be used to test for the presence or absence of specific chromosome regions and is often used to detect small chromosome deletions such as Williams syndrome. This involves using a specific DNA probe which recognizes the region to be tested.
Sample: Peripheral venous blood
Fluorescence in situ hybridization on peripheral-blood specimens is a reliable method to evaluate cytogenetic response in chronic myeloid leukemia.
Chromosomes 13 & 21, Chromosomes 18, X & Y: Chromosome disorders due to non-disjunction of chromosomes 13, 18, 21, X and Y together comprise the majority of the microscopically detectable chromosome disorders. Trisomy 21 or Down syndrome is a condition characterized by intellectual disability, characteristic facial features, congenital malformations and hypotonia. In trisomy 21, there is an increased risk of congenital heart disease, leukemia, deafness, serous otitis media, Hirschsprung’s disease, gastrointestinal atresias, eye disease, including cataracts and severe refractive errors, acquired hip dislocation, and thyroid disease. Adults with trisomy 21 have an increased risk of developing Alzheimer disease. About 95% of cases of trisomy 21 result from an extra copy of chromosome 21.
Prader Willi Syndrome: This genetic disorder causes obesity, intellectual disability and shortness in height. It is a condition caused by an error in one or more genes especially when the paternal genes on chromosome 15 are missing. The can inherit two copies of chromosome 15 from the mother and no chromosome 15 from the father.
Di-George Syndrome: DiGeorge Syndrome (DGS) or 22q11.2, is a primary immunodeficiency disease caused by abnormal migration and development of certain cells and tissues during foetal development. The thymus gland may be affected and T-lymphocyte production may be impaired, resulting in low T-lymphocyte numbers and frequent infections. Around 90% of patients with DGS have a small deletion in chromosome number 22 at position 22q11.2.
William Syndrome: Also Williams-Beuren syndrome, it is a rare genetic disorder characterized by growth delays before and after birth (prenatal and postnatal growth retardation), short stature, a varying degree of mental deficiency, and distinctive facial features that typically become more pronounced with age. It may also be associated with heart (cardiac) defects, abnormally increased levels of calcium in the blood during infancy (infantile hypercalcemia), musculoskeletal defects, and/or other abnormalities.
BRA-ABL: BCR-ABL, also known as a fusion gene, is a mutation that is formed by the combination of two genes, known as BCR and ABL. The BCR gene is normally on chromosome number 22 and the ABL gene on chromosome number 9.
PML-RARA: Promyelocytic leukemia/retinoic acid receptor alpha or PML-RARA refers to an abnormal fusion gene sequence. It is a specific rearrangement of genetic material from two separate chromosomes and is associated with a specific type of leukemia
Sample- Amniotic fluid/ Chorionic Villi/ Cord Blood – FISH test using DNA probes for chromosomes 13, 18,21, X & Y, Di- George syndrome
Prenatal analysis of amniocytes, chorionic villus, cord blood sampling is a useful diagnostic method to identify chromosomal abnormalities associated with a large number of congenital disorders and birth defects. Around 95% of chromosomal abnormalities found prenatally involve abnormality of chromosomes 13, 18, 21, X, and Y, and these may be identified using this FISH panel.
Sample- Bone marrow- FISH test using DNA Probes Del 5q, Del 7q, Inversion 16, BRR-ABL, PML-RARA, AML1/ETO,MLL Break
Paraffin blocks of Breast Solid Tumours for HER2NUE studies
The FISH test is done on breast cancer tissue removed during biopsy to see if the cells have extra copies of the HER2 (human epidermal growth factor receptor 2) gene. The tissue is treated with a substance called formalin, which hardens the tissue and prevents it from breaking down over time. Thin slices of the sample are then embedded in blocks of paraffin. In about 25 percent of breast cancers, the cancer cells have an excess of the HER2 protein. This is caused by a mutation in the HER2 gene. When the HER2 gene mutates, it causes cells in the breast to grow and divide at an uncontrolled rate, leading to tumour growth. is treated with a substance called formalin, which hardens the tissue and prevents it from breaking down over time.
Y-Microdeletion: Y chromosome infertility is caused by deletions of genes in the AZF or sperm-producing regions. These deletions remove several genes, or in rare cases, a single gene. Loss of this genetic material likely prevents the production of one or more proteins needed for normal sperm cell development
DNA Isolation and Storage from Peripheral venous blood, skin biopsy and chorionic villi:
Extraction of DNA from the chorionic villi is the first major step in the molecular determination of foetal haemoglobin genotype.
Prenatal Biochemical Screening
Double Marker (Free beta HCG and PAPP-A) between 10-13+6 weeks gestation from peripheral venous blood of pregnant lady: This first trimester combined test is an effective screening tool for Down syndrome detection with an acceptable low false positive rate. The best timing of screening is between 11 and 12 weeks' gestation.
Quadruple Marker (beta HCG,AFP,UE3,Inhibin-A) between 15-20+6 weeks gestation from peripheral venous blood of pregnant lady: The quad screen test is a maternal blood screening test that looks for four specific substances: AFP , hCG , Estriol, and Inhibin-A. Alpha-fetoprotein (AFP) is a protein made by the developing baby.