Below is a concise but comprehensive paediatric reference for major genetic disorders including aneuploidies, microdeletions, imprinting disorders, and trinucleotide repeat disorders.
Genetic Disorders in Paediatrics
Genetic disorders arise due to abnormalities in chromosome number, chromosome structure, gene function, or gene expression. They are broadly classified into:
- Chromosomal disorders
* Aneuploidies (extra or missing chromosome)
* Microdeletions / microduplications
- Single-gene disorders
* Point mutations
* Trinucleotide repeat disorders
- Epigenetic disorders
* Genomic imprinting abnormalities
1. Aneuploidies
Aneuploidy = abnormal number of chromosomes due to nondisjunction during meiosis.
Normal human karyotype: 46 chromosomes
Examples include trisomies and monosomies.
2. Trisomy 21 (Down Syndrome)
Definition
A chromosomal disorder caused by extra copy of chromosome 21.
Genetics
Types:
- Free trisomy (95%) – meiotic nondisjunction
- Robertsonian translocation (4%) – usually chromosome 14;21
- Mosaic Down syndrome (1%)
Risk factors:
- Advanced maternal age
Pathophysiology
Extra chromosome leads to gene dosage imbalance, affecting brain development and multiple organs.
Clinical Features
Facial features
- Flat facial profile
- Epicanthal folds
- Upward slanting palpebral fissures
- Brushfield spots
- Small ears
- Protruding tongue
Growth and development
- Hypotonia in infancy
- Developmental delay
- Intellectual disability
Skeletal
- Single palmar crease
- Short stature
- Clinodactyly
Systemic associations
Cardiac
- AV septal defect (most common)
- VSD
- ASD
GI
- Duodenal atresia
- Hirschsprung disease
Endocrine
- Hypothyroidism
Hematologic
- Increased risk of leukemia
Neurologic
- Early Alzheimer disease
Diagnosis
- Prenatal screening
* Nuchal translucency
* Maternal serum markers
* NIPT
- Confirmatory test
* Karyotype
Management
No cure; management is supportive.
Cardiac defects
- Surgical correction
Endocrine
- Thyroxine for hypothyroidism
Developmental
- Early intervention programs
- Speech therapy
- Physiotherapy
Monitoring
- Hearing
- Vision
- Thyroid function
- Growth
3. Trisomy 18 (Edward Syndrome)
Definition
Chromosomal disorder due to extra chromosome 18.
Clinical Features
Growth
- Severe intrauterine growth restriction
Face
- Micrognathia
- Low-set ears
- Prominent occiput
Hands
- Clenched fist
- Overlapping fingers
Feet
- Rocker-bottom feet
Systemic
- Congenital heart disease
- Renal anomalies
Prognosis
- Very poor
- Most infants die within first year
Diagnosis
- Prenatal screening
- Karyotype confirmation
Management
- Mainly supportive care
4. Trisomy 13 (Patau Syndrome)
Definition
Presence of extra chromosome 13.
Clinical Features
CNS
- Holoprosencephaly
Face
- Cleft lip and palate
- Microphthalmia
Limbs
- Polydactyly
Cardiac
- Congenital heart defects
Other
- Scalp defects (cutis aplasia)
Prognosis
Very poor; many infants die within weeks or months.
Diagnosis
Karyotype
Management
Supportive care
5. Turner Syndrome
Definition
Chromosomal disorder in females due to monosomy X (45,X).
Genetics
- Complete monosomy
- Mosaicism
Clinical Features
Infancy
- Lymphedema of hands and feet
Childhood
- Short stature
Adolescence
- Delayed puberty
- Primary amenorrhea
Physical features
- Webbed neck
- Shield chest
- Widely spaced nipples
Cardiac
- Coarctation of aorta
- Bicuspid aortic valve
Renal
- Horseshoe kidney
Diagnosis
- Karyotyping
Management
Growth failure
- Growth hormone therapy
Puberty induction
- Estrogen therapy
Monitoring
- Cardiac
- Renal
- Thyroid
6. Noonan Syndrome
Definition
Autosomal dominant disorder affecting RAS-MAPK signaling pathway.
Genetics
Mutations commonly in:
- PTPN11
- SOS1
- RAF1
Clinical Features
Face
- Hypertelorism
- Down-slanting palpebral fissures
- Low-set ears
Growth
- Short stature
Chest
- Pectus excavatum or carinatum
Cardiac
- Pulmonary valve stenosis (most common)
- Hypertrophic cardiomyopathy
Other
- Cryptorchidism in males
- Learning difficulties
Diagnosis
- Clinical features
- Genetic testing
Management
- Cardiac monitoring
- Growth hormone therapy
- Educational support
7. Microdeletion Syndromes
Microdeletion = small chromosomal segment deletion not visible on routine karyotype.
Detected by:
- FISH
- Microarray
DiGeorge Syndrome (22q11 deletion)
Features:
- Cardiac defects (tetralogy of Fallot)
- Abnormal facies
- Thymic hypoplasia → immunodeficiency
- Cleft palate
- Hypocalcemia
Cause
Deletion of chromosome 22q11
Management
- Calcium supplementation
- Cardiac surgery
- Infection management
Williams Syndrome
Deletion: 7q11.23
Features
- "Elfin facies"
- Supravalvular aortic stenosis
- Hypercalcemia
- Friendly personality
Cri-du-chat Syndrome
Deletion: 5p
Features
- High-pitched cry (cat-like)
- Microcephaly
- Intellectual disability
- Facial dysmorphism
8. Genomic Imprinting Disorders
Genomic imprinting = gene expression depends on parent of origin.
Prader-Willi Syndrome
Cause
Loss of paternal chromosome 15 gene expression
Clinical Features
Infancy
- Hypotonia
- Poor feeding
Childhood
- Hyperphagia
- Severe obesity
Other
- Short stature
- Intellectual disability
- Hypogonadism
Management
- Strict diet control
- Growth hormone therapy
Angelman Syndrome
Cause
Loss of maternal chromosome 15 gene expression
Clinical Features
- Severe intellectual disability
- Seizures
- Ataxia
- Frequent laughter ("happy puppet")
Management
- Seizure control
- Developmental therapy
9. Trinucleotide Repeat Disorders
These disorders occur due to expansion of repeated nucleotide sequences in genes.
Mechanism:
- Anticipation: severity increases in successive generations.
Fragile X Syndrome
Cause
CGG repeat expansion in FMR1 gene
Clinical Features
- Intellectual disability
- Long face
- Large ears
- Macroorchidism
- Autism traits
Diagnosis
- DNA testing
Management
- Behavioral therapy
- Educational support
Huntington Disease
Repeat
CAG repeat expansion
Features
- Neurodegeneration
- Chorea
- Psychiatric symptoms
Usually presents in adulthood.
Myotonic Dystrophy
Repeat
CTG expansion
Features
- Muscle weakness
- Myotonia
- Cataracts
- Cardiac conduction defects
Congenital form may present in neonates.
Diagnostic Methods in Genetic Disorders
Common tests include:
Karyotype
FISH
Chromosomal microarray
PCR testing
Next-generation sequencing
Prenatal testing
- Amniocentesis
- Chorionic villus sampling
Genetic Counseling
Important components:
Risk assessment
Carrier screening
Prenatal diagnosis
Family planning guidance
If you want, I can also give a very high-yield NEET-PG / USMLE style summary table of all these genetic disorders (extremely useful for exams).
