High-Yield One-Liners on Genetic Disorders

Chromosomal Disorders 

Disorders of numbers: Aneuploidy which can be of 2 types Trisomy, Monosomy. 

• Disorders of structure.
  • Translocations—Shifting of genetic material can be of two types: balanced and inverted translocations. 
  • Inversions-shifting or turning 180 degrees of a particular genetic segment. 
  • Deletions—Large gene deletions are incompatible with life. Many microdeletions compatible with life are DiGeorge syndrome, in which chromosome 22q11 is involved, and Williams syndrome, in which chromosome 7q11 is affected.
  • Duplications in which the entire gene is duplicated, e.g., the APP gene is located on the 21st chromosome responsible for Alzheimer's disease. It is also seen that certain children with Down syndrome have 3 copies of 21 chromosomes and in other children not having Down syndrome, duplication occurs and there are 2 copies of the APP gene on 21 chromosomes, so they in total have 3 copies and they have earlier onset of Alzheimer's disease.
  • Ring chromosomes: whenever chromosomes are cut, the sticky ends will produce the p and q chromosomes, sticking together to form a ring.

• Chromosomal abnormalities are usually Sporadic, but genetic transmission is common in translocations.
• Most common chromosomal abnormality: Aneuploidy
• Most common aneuploidy: Trisomy
• The most common cause of aneuploidy: Nondisjunction
• Most common aneuploidy Trisomy 16, most trisomy 16 undergoes abortion; hence, they are incompatible with life.
• Most common aneuploidy compatible with life Trisomy 21
• Most common sex chromosomes are based on aneuploidy Klinefelter Syndrome (47-XXY).
• An increased number of repeats leads to increased severity of disease.

Also read: Important Topics for Pediatric Nephrology 2025

UPD (Uniparental Disomy)

What is genomic imprinting?

A phenomenon characterized by selective inactivation of either the maternal or paternal allele.

This means that the phenotypic expression of a gene entirely depends upon the parent of origin. It is a normal phenomenon arising from: Maternal Imprinting: Transcriptional silencing of the maternal allele. Paternal Imprinting: Transcriptional silencing of the paternal allele. Genomic imprinting is a normal phenomenon. Genomic imprinting occurs in the ovum or the sperm before fertilization Then, it is stably transmitted to all the somatic cells through mitosis. It occurs via epigenetic modification, e.g., DNA methylation at CG nucleotides. The number of genes that are imprintable is > 60 (Nelson) or 200-300 (Robbin).

What is imprinting disorder?

It arises due to abnormal phenomena affecting certain genes showing genomic imprinting. It occurs due to

• Deletion
• UPD (Uniparental Disomy)
• Other, e.g., Point mutation, epigenetic aberrant methylation pattern.

Angelman Syndrome

• Obesity can be present in Angelman syndrome, but it is not a defined feature.
• Obesity is a defined feature of Prader-Willi syndrome.
• Prader-Willi syndrome can have intellectual dysfunction but is not as severe as Angelman syndrome.

Also read: Important Topics in Pediatric Infections

Down Syndrome

Q. What are the Hall's criteria for Down syndrome? Hall's 10 cardinal features/ signs for Down syndrome are as follows:

• Poor Moro Reflex.
• Hypotonia
• Flat facial profile
• Upward slanting palpebral fissure.
• Small, dysplastic, rounded ears.
• Redundant skin around a short neck.
• Single transverse palmar crease
• Large Hyperextensible joints.
• Short 5th digit with clinodactyly.
• Pelvic dysplasia.

Sonographic Markers for Down Syndrome

• Brachycephaly or shortened frontal lobe
• Clinodactyly (hypoplasia of the 5th digit middle phalanx)
• Echogenic bowel
• Flat facies
• Echogenic intracardiac focus
• Nasal bone absence or hypoplasia
• Nuchal fold thickening
• Renal pelvis dilation (mild)
• "Sandal gap" between first and second toes
• Shortened ear length
• Single transverse palmar crease
• Single umbilical artery
• Short femur
• Short humerus
• Widened iliac angle

Turner Syndrome

Most consistent features of Turner Syndrome

Growth failure is seen in 50 to 90% of the cases

Streak gonads can lead to infertility.

Also read: High-Yield One Liners in Pediatric Pulmonology

Q. Which variety of Turner syndrome is associated with low IQ?

Ans.

Isochromosome causing Turner syndrome.

Before 12 years of age, no estrogen or progesterone should be given.

The image shows the short 4th metacarpal, which is also known as the metacarpal sign.

It is a common feature of Turner syndrome.

Noonan Syndrome

• Noonan Syndrome patients with PTPN-11 gene mutations grow less well and show less response to GH therapy.
• Reason in post-signalling defect leading to partial GH resistance, manifesting as raised serum GH and low IGF-1 level.

What are microdeletion syndromes? 

• Arise due to deletions smaller than 5 Mbps.
• These diseases are not identified by conventional karyotyping.
• Best diagnosed using FSH (fluorescent in situ hybridization).

Genetic Skeletal Disorders

• Hallmark of chondrodysplasias: Disproportionate short stature
• Lethal neonatal dwarfism:
• Usually fatal: thanatophoric dysplasia and campomelic dysplasia.
• Often fatal: Jeune syndrome (Thoracic Asphyxiating dystrophy)
• Occasionally fatal: Ellis-Van-Creveld syndrome

Also read: Frequently asked questions in Pediatric Cardiology

Q. In a suspected skeletal dysplasia, no positive family history was elicited. What are the likely reasons?

Ans. 

• No family history is seen due to the following conditions:
• New mutation in AD condition: Achondroplasia
• AR inheritance
• Germline mosaicism

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