We provide clinical diagnostics and genetic counselling for the following conditions at Best Paediatric Hospitals in India.

Multiple congenital abnormalities

Congenital anomalies are brought on by the developing foetus in the uterus. Five categories of congenital abnormalities include:

Chromosome Abnormalities

The 46th chromosome, of which twenty-three come from the father and twenty-three from the mother, is a typical chromosome that transmits gene structures from one generation to the next. The infant may be born with major health conditions like Down syndrome if the foetus develops without 46 chromosomes or if some of the chromosomes are duplicated or absent.

Single-Gene Abnormalitie

Even when the number of chromosomes is normal, one or more of their genes may be defective. 

Conditions during pregnancy that can cause abnormalities in the foetus

In particular during the first nine weeks, if the mother has specific infections like chicken pox or rubella, or if she develops chronic conditions like diabetes, hypertension, or autoimmune diseases like lupus.

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).

Unknown cases.

Prenatal onset of growth retardation or failure to thrive

Intrauterine growth restriction, which can start at any point during pregnancy, is when the foetus is smaller than anticipated for the number of weeks of pregnancy. Early-onset is frequently brought on by genetic abnormalities, maternal illness, or serious placental issues. Late onset, which typically occurs after 32 weeks, is typically associated with other issues. The foetus may only receive small amounts of oxygen when there is insufficient blood flow through the placenta, which results in the foetal heart rate decreasing, leaving the foetus at serious risk.

Children with dysmorphic features or syndrome diagnosis

Due to the unique pattern of clinical symptoms that are frequently present on infant physical examinations, many genetic disorders are visible and diagnosable during the neonatal era. The 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 are some of the more common genetic dysmorphic conditions neonatal practitioners are most likely to encounter in a foetus. From head to toe, the newborn is physically examined for signs of facial asymmetries, deformities, or deformations as part of the genetic dysmorphology evaluation. 

Developmental or intellectual disability of unknown causes

A category of disorders known as developmental impairments is brought on by poor linguistic, behavioural, or learning abilities. Intellectual impairment, traditionally known as mental retardation, is characterised by difficulties with cognitive processes like learning and problem-solving as well as adaptive processes like independent living and communication. A person with an intellectual disability has a lower than normal IQ and lacks the necessary life skills. 

Family history of sibling’s death of unknown causes

The only group of hereditary metabolic diseases proven to be accountable for sudden infant death syndrome is fatty acid oxidation (SIDS). Despite the rarity of these abnormalities, it has been crucial to pinpoint those instances where an inherited flaw is most certainly the cause of death or significantly increases the risk of infant death. Such cases of sudden unexpected death in infancy are vital to take into account because there is frequently a history of sickness before death in SIDS cases.

Bad obstetric history or fertility

If a woman has gone through two or more of the following situations in the past, she is said to have "poor obstetric history (BOH)”.

Consecutive spontaneous abortions

Following are the outcome for consecutive spontaneous abortions:

Early neonatal deaths

Stillbirths

Intrauterine fetal deaths

Intrauterine growth retardation

Congenital anomalies in the fetus

Infectious causes

Following are the infectious causes,

The examination of infertility should include the collection of cervical cultures.

Empiric antibiotics ought to be administered before invasive tests like HSG. 

Primary amenorrhea

Primary amenorrhea is the absence of menstruation by the age of 16 in the presence of secondary sexual characteristics and normal growth. A workup for primary amenorrhea should begin if at the age of 13 menses have not begun and the beginning of puberty, such as breast development, is absent. The most frequent causes of primary amenorrhea are genetic or inborn disorders. Disorders of the ovaries, pituitary gland, brain, or uterus can cause amenorrhea. Amenorrhea can be brought on by strenuous exercise, rapid weight loss, physical disease, and stress. Primary amenorrhea is the absence of menstruation at the anticipated time. The typical cut-off age for primary amenorrhea is 15 years old.

Chromosome instability syndrome

A category of genetic diseases known as chromosomal instability syndromes (CIS) are transmitted in an autosomal recessive fashion and are often characterised by delays in both mental and physical growth. Other health issues are also common among CIS patients, such as various degrees of dysmorphia, organ and system dysfunction, and a high propensity for malignancy. People with CIS are frequently children, and these illnesses are frequently fatal. Typically, diagnosis is challenging due to the variety and complexity of symptoms that CIS patients present with. The discovery of genes involved in this group of diseases/disorders at the molecular level has shown that CIS is characterised by defects in DNA repair systems and genomic instability.

Family history of known genetic disorder

Genetic illnesses include sickle cell disease, cystic fibrosis, and Tay-Sachs disease often entails the inheritance of a specific faulty disease-causing gene. Every generation of descendants has a chance to receive the disease-causing gene because the defective gene is passed down through a family. Genetic disorders can be monogenic, multifactoral, or chromosomal.

Positive antenatal screening

The antenatal screening tests provide the results as either "screen positive" or "screen negative". A positive screen result indicates a higher risk of considering a prenatal diagnosis. It does not represent the fact that the baby is affected. The women showing screen-positive results may proceed to have normal babies. The screen-negative result does not represent a higher risk. It does not mean that an affected pregnancy is completely excluded.

Cancer

It is the most common type of human genetic disease. The transition of cells from normal cells to malignant cells is initiated by the changes within the DNA of the cells, which are also known as mutations. Some people are born with gene mutations that are inherited from their mother or father. The damaged gene puts them at a higher risk for cancer when compared with other individuals. When cancer occurs because of an inherited gene mutation, it is referred to as hereditary cancer. 

Interpretation of cytogenetics or molecular genetics report

The study of chromosomes and associated abnormalities is known as cytogenetics. Karyotyping, another name for chromosome analysis, involves pairing homologous chromosomes. Oncologic and hematologic problems must be diagnosed using cytogenetic analysis. Molecular genetics makes use of DNA technology's mechanisms to study gene mutations. 

Test performed in Medical Genetics Laboratory

A sort of laboratory test called kyrotyping looks at and analyses chromosomes and any anomalies, such dividing cells. The chromosomal pairs are organised according to size and appearance. The karyotype test aids in identifying any damaged or missing chromosomes. 

Karyotyping of the following sample or specimens

Peripheral venous blood is used in this case. A blood sample is taken from a vein in your arm to check for any chromosomal anomalies when a person has leukaemia, lymphoma, myeloma, myelodysplasia, or another disease and an acquired chromosome abnormality is suspected; when pregnancy screening tests are abnormal; or when symptoms of a disorder associated with chromosomal abnormalities are present in family members.

Prenatal diagnosis during pregnancy- Chronic villi, amniotic fluid, cord blood

For testing the pregnancy loss, the obstetrician or gynaecologist takes cord blood, amniotic fluid, or chorionic villi samples from the placental lining. Screening for neural tube defects, chromosome abnormalities, and gene mutations that cause genetic disorders and birth defects such as spina bifida, cleft palate, Down syndrome, Tay-Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, and fragile X.

Bone Marrow

Two types of bone marrow tests involving bone marrow aspiration and biopsy are available. It is carried out to identify the Philadelphia chromosome, which is observed among almost 85% of the individuals having chronic myelogenous leukemia (CML). It is also carried out in cases of leukemia, lymphoma, myeloma, myelodysplasia, or occurrence of any other cancer type and when an acquired chromosome abnormality is suspected.

Product of conception (abortus)

A chromosome problem, which is a possible reason for the abortion, is ruled out using fibroblast culture on samples of miscarriage tissues, also referred to as products of conception.

Fluorescence In-situ Hybridization (FISH)

It is used for testing the presence or absence of specific chromosome regions and is most often used for diagnosing small chromosome deletions involving Williams syndrome. It includes the use of a specific DNA probe that identifies the region to be tested.

Sample

Peripheral venous blood 

Using peripheral blood samples and fluorescence in situ hybridization, cytogenetic response in chronic myeloid leukaemia can be accurately assessed.  

Chromosomes 13 & 21, Chromosomes 18, X & Y

Chromosome abnormalities caused by non-disjunction of chromosomes 13, 18, 21, X, and Y combined make up the majority of the microscopically identifiable chromosome disorders. Chromosomes 13 and 21, Chromosomes 18, X, and Y Intellectual difficulty, distinctive facial traits, congenital abnormalities, and hypotonia are all characteristics of trisomy 21, also known as Down syndrome. Congenital heart disease, leukaemia, serous otitis media, Hirschsprung's disease, gastrointestinal atresias, eye disease, including cataracts and severe refractive errors, acquired hip dislocation, and thyroid disease are all more common in people with trisomy 21. Trisomy 21 adult patients have a higher chance of developing Alzheimer's disease. A second copy of chromosome 21 is the cause of trisomy 21 in about 95% of instances.

Prader Willi Syndrome

It is a type of genetic disorder that results in obesity, intellectual disability, and shortness of height. This condition occurs due to an error in one or more genes, mainly in the case when paternal genes on chromosome 15 are missing. It inherits two copies of chromosome 15 from the mother and none of chromosome 15 from the father.

Di-George Syndrome

It is also known as 22q11.2 ,which is a primary immunodeficiency disorder brought on by aberrant cell and tissue migration and development during foetal development. Low T-lymphocyte counts and recurrent infections may result from thymus gland dysfunction and reduced T-lymphocyte generation. Approximately 90% of individuals with DGS have a minor deletion at position 22q11.2 on chromosomal number 22.

William Syndrome

It is also known as Williams-Beuren syndrome, which is a rare genetic disorder characterised by growth delay 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 is correlated with heart (cardiac) defects, abnormally increased levels of calcium in the blood during infancy (infantile hypercalcemia), musculoskeletal defects, and other abnormalities. 

BRA-ABL

It is also known as a fusion gene, which shows a mutation formed by combining two genes involving BCR and ABL. The ABL gene is often located on chromosome 9, while the BCR gene is typically located on chromosome 22.

PML-RARA

It is also known as promyelocytic leukemia or retinoic acid receptor alpha. It is an abnormal fusion gene sequence. It is a particular genetic rearrangement originating from two distinct chromosomes and is connected to a particular kind of leukaemia.

Sample- Amniotic fluid/ Chorionic Villi/ Cord Blood – FISH test using DNA probes for chromosomes 13, 18,21, X & Y, Di- George syndrome

Amniocyte, chorionic villus, and cord blood studies performed during pregnancy can help doctors diagnose chromosomal abnormalities linked to a variety of congenital diseases and birth problems. This FISH panel can be used to identify abnormalities on chromosomes 13, 18, 21, X, and Y, which make up around 95% of chromosomal abnormalities discovered prenatally.

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 performed on breast cancer tissue retrieved during biopsy in order to determine whether the cells have extra copies of the HER2 (human epidermal growth factor receptor 2) gene. A chemical called formalin is used to cure the tissue, which hardens it and keeps it from degrading over time. The material is then cut into thin slices and placed into blocks of paraffin. The HER2 protein is overexpressed in the cancer cells of roughly 25% of breast tumours. The HER2 gene mutation is to blame for this. The HER2 gene mutation causes breast cells to proliferate and divide uncontrollably, which promotes the development of tumours. Formalin, a chemical that hardens the tissue and keeps it from degrading over time, is used to treat the tissue.

Molecular study

Y-Microdeletion: Deletions of genes in the AZF or sperm-producing areas lead to Y chromosomal sterility. These deletions eliminate numerous genes, or in unusual circumstances, just one gene. It's possible that if this genetic information is lost, one or more proteins required for typical sperm cell growth won't be produced.

DNA Isolation and Storage from Peripheral venous blood, skin biopsy and chorionic villi: The first significant step in the molecular determination of the foetal haemoglobin genotype is the extraction of DNA from the chorionic villi.

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 combination test performed during the first trimester is a reliable screening method for identifying Down syndrome with a manageable low false positive rate. Ideally, screening should take place between 11 and 12 weeks of gestation.

Quadruple Marker (beta HCG,AFP,UE3,Inhibin-A) between 15-20+6 weeks gestation from peripheral venous blood of pregnant lady: The AFP, hCG, estriol, and inhibin-A are the four particular substances that the quad screen test searches for in maternal blood. The developing foetus produces a protein called alpha-fetoprotein (AFP). So feel fre to reach out to the Paediatric center in India - Manipal International Patient Care.