Down Syndrome and Clinical Features

Down Syndrome

• Parents who are carriers of the genetic translocation for Down syndrome have a higher risk of having a child with the condition.

Clinical Features

• Mental retardation, hypotonia, and delayed developmental milestones
• Craniofacial features: fine silky hair, mild microcephaly, flat occiput, small dysplastic ears, upward slanting palpebral fissures, epicanthic folds, and speckled irides (Brushfield spots)
• Small nose, flat nasal bridge, protruding tongue, open mouth, and high-arched palate
• Hand and feet features: simian crease, short and broad hands, hypoplasia of middle phalanx of 5th finger, and gap between 1st and 2nd toes

Health-related Problems

• Cardiovascular problems (50%): AVSD, VSD, ASD, and PDA
• Endocrine problems (1-4%): congenital or acquired hypothyroidism, diabetes mellitus
• Gastrointestinal problems (5%): duodenal, esophageal, and anal atresia, Hirschprung's disease, and celiac disease
• Haematological problems: acute leukemia, transient myeloproliferative disease
• Neurological problems: epilepsy, severe behavioral problems, Alzheimer's disease, memory problems, and autism

Management

• Eye exam should be performed in the newborn period or at least before 6 months of age to detect strabismus, nystagmus, and cataracts
• Thyroid function tests should be done in the newborn period and repeated at 6 and 12 months, and then annually
• Celiac disease screening should begin at 2 years and repeated if signs develop
• Hematology: CBC with DLC at birth to evaluate for leukemia
• Atlanto-axial instability: X-ray at 3 to 5 years of age
• Alzheimer's disease: adult with Down syndrome has an earlier onset of symptoms

Counseling

• Recurrence risk: 1-4% for trisomy 21, increased by 1% to maternal age-related risk
• New translocation (mutation): random risk as the general population
• If the mother is a carrier of 14q:21q translocation (45 xx): 10-15% recurrence risk
• If the mother is a carrier of 21q:21q translocation (45 xx): 100% recurrence risk

Mortality

• Average life span: 25-50 years
• Most likely cause of death: CHD, recurrent infections (in infancy), accidents due to mental retardation (in older children), atlanto-axial instability, and leukemia
• Improved survival due to increased placements of infants in rehabilitation homes and changes in treatment for common causes of death
• Survival is better for males

Down Syndrome

• Also known as "trisomy 21", a genetic disorder caused by the presence of all or part of a third copy of chromosome 21.
• Typically associated with physical growth delays, characteristic facial features, and mild to moderate intellectual disability.

Clinical Features

• Mental retardation
• Hypotonia
• Delayed developmental milestones
• Cranio-facial features:
  • Fine silky hair
  • Mild microcephaly
  • Flat occiput
  • Small dysplastic ears
  • Upward slanting palpebral fissures
  • Epicanthic folds
  • Speckled irides (Brushfield spots)
• Hands and feet:
  • Simian crease
  • Short, broad hands
  • Hypoplasia of middle phalanx of 5th finger
  • Gap between 1st and 2nd toes

Health-Related Problems

• Cardiovascular problems (50% of DS): AVSD, VSD, ASD, and PDA
• Endocrine problems:
  • Thyroid problems (1% congenital, 4% acquired hypothyroidism)
  • Diabetes mellitus
• Gastrointestinal problems (5%):
  • Duodenal, esophageal, and anal atresia
  • Hirschsprung's disease
  • Celiac disease
• Haematological problems:
  • Acute leukemia
  • Transient myeloproliferative disease
• Neurological problems:
  • Epilepsy
  • Severe behavioral problems
  • Alzheimer's
  • Memory problems
  • Autism
• Sleep problems:
  • Sleep apnoea
  • Other sleep disturbances
• Skeletal problems:
  • Flat foot
  • Atlantoaxial subluxation
• Visual problems:
  • Refractive disorder
  • Squint
  • Nystagmus
  • Cataract
• Hearing problems:
  • Hearing loss
  • Conductive hearing loss
  • Chronic otitis media

Feeding Problems

• Chocking with feeds
• Recurrent pneumonia
• Unexplained failure to thrive (celiac disease)
• Constipation:
  • Restricted diet
  • Decreased fluid intake
  • Hypotonia
  • Hypothyroidism
  • Hirschsprung disease

Reproduction

• Women with DS are fertile and may become pregnant

Incidence and Genetic Types

• Incidence in the general population: 1/600 - 1/800 births
• Genetic types of DS:
  • Nondisjunction (trisomy 21): 95%
  • Translocation of chromosome 21: 4%
  • Mosaicism: 1%

Risk Factors

• Advancing maternal age (usually women of age 35 and above)
• Trisomic mothers