Down Syndrome or Trisomy 21: Chromosomal disorder

Trisomy 21 or  Down Syndrome was first described by John Langdon Hayden Down a Physician ( 1828-1896 AD) in The London Hospital in 1866 AD.In 1959, Lejeune and Jacobs et al independently determined -trisomy 21 as cause of Down Syndrome.

March 21st every Year is Marked  as ” Down Syndrome Day” – 3rd month 21st

Karyotype–

1. Trisomy 21: 47 XX or XY +21 . Usually caused by an extra copy of Chromosome 21
2. Translocational type- 46 XX, der ( 14;21)(q10;q10),+21
3. Mosaic type- 46 XX/ 47 XX ,+21

Most common of the chromosomal disorders ( incidence 1 in 700 births).Risk increases with maternal age. Significant increase in risk with Maternal age above 40 years. 1:2000 in  under 25 years, 1: 300 at 35 years and 1:100 at 40 years. Co-relation with maternal age suggests that meiotic  non-disjunction of Chromosome 21 occurs in Ovum.

Male:Female ratio is 1.15:1 not much difference.

Pathogenesis

1. Meiotic non-dysjunction (95%)
2. Robertsonian translocation (4%)
3. Mosaicism due to miotic non-dysjunction during the embryogenesis. (1%) : Mosaics are people having 2 or more populations of cells within individuals.  They have variable features and milder.

Clinical features-

Severe mental retardation- most common cause of genetic mental retardation.  IQ is generally low to very low.

Facial  features :

• Mongoloid facies-flat face,low-bridged nose, epicanthal folds, mongoloid slant of eyes
• brachycephaly commonly , microcephaly, delayed closure of  fontanels, a patent metopic suture
• Absent frontal and sphenoid sinuses, and hypoplasia of the maxillary sinuses may be seen.
• low-set ears ,dysplastic ears-small ear with overfolded helix
• hypertelorism –wide set eyes
• high arched palate,open mouth with protruded and furrowed tongue ( macroglossia)

Eyes-

• Brushfield spots-speckled appearance of the iris
• Cataract and squint sometimes
• Refractive error and nystagmus

Hands-

• Simian hand- short broad hands with short stubby fingers
• Simian Crease- Single palmar flexion crease.
• Clinodactyly -( Hypoplasia of the middle phalanx of 5^th finger producing incurving little finger)
• Dermatoglyphics-  more than 8 ulnar loops on fingers and distal axial triradii becomes obtuse.

Foot-

• Sandal gap- Increased gap between 1^st and 2^nd toe
• Sub-hallucial pad of fat
• Single deep longitudinal plantar crease

Cardiovascular System-Congenital heart defects- Endocardial cushion defect leads to formation of an atrioventricular canal ( a common connection between all 4 chambers), VSD, ASD, PDA

GI system – Duodenal atresia ( ‘ double bubble ‘ sign), Hirchsprung disease, tracheo-esophageal fistula, Imperforate anus.

Other System-

• Muscular hypotonia
• Broad short neck, Short height, Growth retardation
• Atlantoaxial subluxation with spinal cord compression <1 : A delay in recognizing atlantoaxial and atlanto-occipital instability may result in irreversible spinal-cord damage and add disability like visual and auditory loss.
• Infertility
• Personality- Cheerful, fond of Music.
• Premature Aging.
• Umbilcal hernia and diastasis rectii

Increase susceptibility to-

• Increased risk ( 15-20 X) of Acute Lymphoblastic Lymphoma- Trisomy 21, GATA 1 mutation and unknown genetic alternation.
• Alzheimer disease ( by age 40 virtually all will develop Alzheimer Disease)
• Coeliac disease may be associated .
• Increased susceptibility to infection (pneumonia, otitis media, sinusitis, pharyngitis, periodontal disease)
• Autoimmune hypothyroidism and Hashimoto disease
• Hyperuricemia, Diabetes Mellitus,

Prenatal Diagnosis-

1. In-utero:  Triple test using Maternal serum levels of alpha-fetoprotein, hCG, and unconjugated  estriol.
2. Ultrasonography- increased nuchal fold >4 mm, failure to visualize fetal nasal bone at age 11-13 weeks POG,femur and the humerus tend to be shortened.
3. Amniocentesis
4. Chorionic Villi sampling
5. Percutaneous umbilical blood sampling (PUBS)

 

Prognosis:

Down syndrome decreases prenatal viability and increases prenatal and postnatal morbidity as well. About 75%  with trisomy 21 die in fetal life.~ 85% of infants survive to age 1 year, and 50% can be expected to live longer than age 50 years. Down Syndrome is compatible to life . With good medical care , current median age at death is 47 years.

10 Questions about Down syndrome : FAQ

Reference:

• Robbins and Cotran Pathological Basis of Disease
• Langman’s Medical embryology.
• USG measurement in down Syndrome
• Kundu Bedside Medicine
• Kaplan’s Lecture notes
• Medscape-Emedicine