Pediatric Pathology

Introduction:

Pediatric diseases are conditions seen among the population from birth to 16 years of age. The very first year of infancy is more vulnerable to diseases. Therefore, crossing over the first year is a sigh of major relief. However, various diseases are associated with different age groups. It is alarming to witness a higher mortality rate among this age group.

What Are the Structural Deformities Seen in Newborn Babies?

Congenital anomalies are structural defects seen in infants at birth. About three percent of infants show a cosmetic or functional defect. On clinical examination, one can observe birth defects such as:

• Polydactyly (extra digits).

• Syndactyly (fusion of digits).

• Amniotic bands seen in underdeveloped fingers.

• Cleft lip caused due to trisomy 13.

• Dysmorphogenesis has been seen in the brain and heart's mid-maldevelopment, causing mid-face structures' malformation.

• Oligohydramnios is caused due to decreased amniotic fluid due to various reasons. Leakage of amniotic fluid or placental insufficiency. As a result, the infant develops flattened facial features and deformed feet.

• Agenesis (complete absence of an organ).

• Aplasia (incomplete development).

• Hypoplasia (underdevelopment of an organ).

• Conditions like atresia are the absence of an organ opening like that of a hollow visceral organ or duct such as the intestines.

What Are the Causes of Congenital Anomalies?

There are mainly three causes of birth defects:

1. Genetic.

2. Environmental.

3. Unknown.

What Are Genetic Anomalies?

Genetic disorders are chromosomal abnormalities. Examples are Down syndrome, Turner syndrome, and Klinefelter syndrome. These are not familial. These conditions develop as a result of gametogenesis. Single gene mutations seen in mendelian disorder also cause malformations. Such as, mutation seen in sonic hedgehog homolog (SHH) causes holoprosencephaly. This causes underdevelopment of the forebrain and midface. Also, a single gene mutation was seen in PAX6, causing the absence of the iris (aniridia).

What Are the Environmental Factors Causing Genetic Disorder?

Environmental factors such as drugs, irradiation, and viral infections can cause anomalies. Viral infections such as rubella embryopathy can cause tetrad defects of congenital heart disease, cataracts, deafness, and mental retardation. Currently, there is a vaccination for maternal rubella virus and rubella syndromes.

Drugs of teratogenic nature constitute less than one percent of malformations. Some of the drugs are Warfarin (oral anticoagulant), Thalidomide, androgenic hormones, Folate, alcohol, anticonvulsants, and Nicotine. One of the commonly available and used drugs is alcohol which causes prenatal and postnatal growth retardation, facial anomaly (maxillary hypoplasia, microcephaly, and short palpebral fissures), and psychomotor disorders, collectively known as fetal alcohol syndrome.

Nicotine causes fetal abortions. Pregnant mothers with hyperglycemia cause diabetic embryopathy, causing cardiac anomalies, increased body fat, and poor immune system in infants. Most congenital conditions are idiopathic. Sudden infant death syndrome (SIDS): Also known as crib death or cot death. This is caused during the first year of infancy without any reason.

What Are the Infections Acquired Through Direct Mother's Blood?

Transplacental or hematological infections are pooled directly from a mother's blood to the fetus. Infections caused by Toxoplasma, Rubella virus, Cytomegalovirus, Herpes virus, and other microbes are together known under the acronym- TORCH. These agents cause fever, anemia, chorioretinitis, hepatosplenomegaly, pneumonia, congenital cytomegalovirus, syphilis, and encephalitis.

What Are Some of the Pathological Conditions Associated With Infants?

• Necrotizing Enterocolitis (NEC): It causes a high morbidity and mortality rate in infants (premature infants). Bacterial colonization of the gut leading to mucosal bleeding and immature bowel is one of the aggravating factors.

• Hemangiomas: It is one of the most common tumor occurrences seen in infants. They occur on the skin, scalp, and face and are elevated, irregular, and port wine stains. These occur at birth and regress as the child grows older.

• Malignant Neoplasms: Like Wilms tumor, which is the cancer of the kidney. It is also known as nephroblastoma and is seen in kids from four to five years of age. This tumor is caused due to chromosomal errors like WT-1, which can be localized, as seen in chromosome 11. Other conditions like leukemia in children are caused due to proliferation of hematopoietic cells. This can be both an acute and chronic condition. The causes may vary from lack of bone marrow cell production to accumulation of malignant cells in tissues. Leukemia in children is the most common pediatric condition. Malignant conditions like retinoblastoma are seen due to deformity in the developing retina of the children. It occurs due to the mutation of the long arm of chromosome 13q14, which is a tumor suppressor gene, and conditions like teratomas that arise from germ cell layers or embryological cells are also observed.

• Wilms Tumor: These tumors are associated with kidneys. Seen in two to five years of age group. It causes mental retardation, aniridia (complete or partial absence of color of the iris), and genital abnormalities. Many syndromes like WAGR syndrome, Denys- Drash syndrome, and Beckwith-Wiedemann syndrome give rise to Wilms tumor. Around five percent of this tumor is composed of anaplasia. Here, cells are large, hyperchromatic, pleomorphic nuclei, and abnormal mitoses are seen. On palpation, the tumor mass can be appreciated down the pelvis region. The prognosis is good. It can be treated with nephrectomy and chemotherapy.

What Are the Diagnostic Tools Used in Pediatric Diseases?

• Histological Examination: During these studies, tissue biopsies are collected, paraffin-embedded, and further stained to study under a microscope. For example, the study of renal biopsies has shown many histopathological features like acute tubular necrosis, serum creatinine level of <1.2mg/dl, renal amyloidosis, and glomerulonephritis (GN), crescentic glomerulonephritis (Cres GN) and other variations.

• Clinical and Radiographic Findings: In clinical evaluation, procedures like auscultation, percussion, pulse, and breathing per minute(BPM) are evaluated by the physician. Conditions like chest discomfort, pneumonia, foreign body aspiration, and cystic formation will require X-rays and other high diagnostic tests like CT and MRI.

• Ancillary Studies: Like chromosome or cytogenetic analysis, immunoperoxidase stains, and electron microscopy.

• Fluorescence in Situ Hybridization (Fish): This is used in chromosome-specific sequences labeled with fluorescent dyes. Samples can be obtained from biopsies, cells of amniocentesis, chorionic villus, or umbilical cord blood. The obtained sample can be observed under a fluorescent microscope. This study helps in the detection of numeric abnormalities of chromosomes known as aneuploidy. It can also be used for microdeletion, mapping of genes, karyotyping, and gene amplification.

• Molecular Detection: This technique-sensitive procedure helps in identifying mutations at the DNA level. Around one lakh cells are collected to carry out this test. A small amount of whole or dried blood is enough for polymerase chain reaction (PCR) amplification. Helps in the diagnosis of single gene mutations, as seen in the case of Mendelian disorder.

• Direct Gene Diagnosis: Detected in the presence of the normal and mutated genes. It is further cloned, and its sequence of nucleotides is identified. The main disadvantage of this study is the absence of defective genes due to multifactorial (polygenic) factors. This technique helps to identify heterozygous or homozygous mutant genes passed to the next generation. These studies have been used in Huntington's disease and adult polycystic disease. Single-nucleotide polymorphism (SNP) is again a genetic marker to observe transmission from parent to child. It has been used to study diseases like diabetes, hypertension, and heart disease.

What Are the Management of Pediatric Conditions?

• Early diagnosis of gene defect before clinical manifestation.

• Ultrasonography (USG) detection.

• Avoiding drugs causing toxicity or fetal abnormalities in children.

• Post-delivery handling of the baby with utmost care.

• Blood tests.

• Timely vaccination status.

Conclusion:

Most pediatric conditions cause mortality in larger numbers. Hence the early detection and prevention of such conditions is the need of the hour. A healthy generation marks the healthy growth of the community. Awareness programs, early screening, and accessibility of treatment to every class of society are required. New global and governmental policies promoting the health sector are welcomed.