Down’s syndrome

BY- DR. KAJAL (PT)

Definition & Introduction

 Down syndrome was first described by an English physician John Langdon Down in
1866, but its association with chromosome 21 was established almost 100 years later by
Dr. Jerome Lejeune in Paris.
 It is the presence of all or part of the third copy of chromosome 21 which causes Down
syndrome, the most common chromosomal abnormality occurring in humans.
 It is also found that the most frequently occurring live born aneuploidy is trisomy 21 that
causes this syndrome.
Etiology

 The majority of patients with Down syndrome have an extra copy of chromosome 21.
 There are different hypothesis related to genetic basis of Down syndrome and association of
different genotypes with the phenotypes.
 Among them is gene dosage imbalance in which there is an increased dosage or number of genes
of Hsa21, which results in increased gene expansion.
Pathophysiology

 An extra copy of chromosome 21 is associated with Down syndrome, which occurs due to
the failure of chromosome 21 to separate during gametogenesis resulting in an extra
chromosome in all the body cells.
 Robertsonian translocation and isochromosome or ring chromosome are the other 2
possible causes of trisomy 21.
 Isochromosome is a condition when 2 long arms separate together instead of the long and
short arm while in Robertsonian translocation.
 This occurs in 2% to 4% of the patients. The long arm of chromosome 21 is attached to
another chromosome, mostly chromosome 14.
 In mosaicism, there are 2 different cell lines because of error of division after fertilization.
Clinical Features

 Congenital Cardiac Defects

 Gastrointestinal (GI) Tract Abnormalities
 Duodenal and small bowel atresia or stenosis, annular pancreas, imperforate anus,
gastroesophageal reflux
 Hematologic Disorders
 HANDS- neutrophilia, thrombocytopenia, and polycythemia
 Transient abnormal myelopoiesis or transient leukemia
 Chronic myeloid leukemia
 Neurologic Disorders
 Reduced brain volume especially hippocampus and cerebellum
 Joint laxity that causes decreased gait stability and increased energy requirement for physical exertion
 Prone to decreased bone mass and increased risk of fractures due to the low level of physical
activity, while the ligamentous laxity predisposes these patients to atlantoaxial subluxation
 Alzheimer disease
 Mild to moderate learning disability
 Endocrinological Disorders
 Hypothyroidism
 Abnormalities in sexual development
 Musculoskeletal Disorders
 Hypotonia, increased ligamentous laxity & decreased bone mass.
 Refractive Errors and Visual Abnormalities
 Blepharitis, keratoconus, cataract, retinal anomalies, strabismus, amblyopia, nystagmus,
refractive errors, glaucoma, iris anomalies and optic nerve anomalies.
 Otorhinolaryngological (ENT) Disorders
 Hearing deficits
 Hearing loss is usually conductive
Evaluation

 Ultrasound between 14 and 24 weeks of gestation can be used as a tool for diagnosis
based on the soft markers like increased nuchal fold thickness, small or no nasal bone and
large ventricles.
 Amniocentesis and chorionic villus sampling had widely been used

 PCR
 Karyotyping
Differential Diagnosis

 Congenital hypothyroidism
 Mosaic trisomy 21 syndrome
 Partial trisomy 21(or 21q duplication)
 Robertsonian trisomy 21
 Trisomy 18
 Zellweger syndrome or other peroxisomal disorders
Management

 Parental education
 Treatment is basically symtomatic and complete recovery is not possible.
 These patients should have their hearing and vision assessed and as they are more prone
to have a cataract, therefore timely surgery is required.
 Thyroid function tests should be done on a yearly basis and if deranged should be
managed accordingly.
 A balanced diet, regular exercise, and physical therapy are needed for the optimum
growth and weight gain, although feeding problems do improve after the cardiac surgery.
 Cardiac referral should be sent for all the patients regardless of the clinical signs of
congenital heart disease which if present should be corrected within the first 6 months of
life to ensure optimum growth and development of the child.

 Other specialties involved include a developmental pediatrician, pediatric pulmonologist,

gastroenterologist, neurologist, neurosurgeon, orthopedic specialist, child psychiatrist,
physical and occupational therapist, speech and language therapist, and audiologist.
Spina Bifida
Definition & Introduction

 Spina bifida is a congenital malformation in which the spinal column is split (bifid) as a
result of failed closure of the embryonic neural tube, during the fourth week post-
fertilization.
 In its commonest and most severe form, myelomeningocele (MMC; also termed open
spina bifida or spina bifida aperta), the spinal cord is open dorsally, forming a placode on
the back of the fetus or newborn baby that frequently rests on a meningeal sac (then
named spina bifida cystica.
 The vertebrae at the level of the lesion lack neural arches, and so are incomplete dorsally.
Classification

 Occulta
 Closed neural tube defects
 Meningocele
 Myelomeningocele
Spina Bifida Occulta

 Mildest and most common form in which one or more bones of the spinal column (called
vertebrae) are malformed.
 The name “occulta,” which means “hidden,” indicates that a layer of skin covers the
opening in the bones of the spine.
 It is often found by accident on an x-ray or similar test.
 This form of spina bifida very rarely causes disabilities or symptoms.
Closed neural tube defects

 Diverse group of defects in which the spine may have malformations of fat, bone, or the
meninges.
 Many of these neural tube defects require surgery in childhood.
 People with this type of spina bifida may have weakness of the legs and trouble with
bowel and bladder control.
 These issues may change or progress as children grow.
 It is important to have close follow-up with doctors to minimize these changes as much as
possible.
Meningocele

 A sac of spinal fluid pokes through the spine.

 This fluid is normally only around the brain and spine, but a problem with the bony
covering over the spine allows it to poke out in this case.
 The malformation contains no nerves and may or may not be covered by a layer of skin.
 Individuals with meningocele may have minor symptoms.
Myelomeningocele

 Most severe form of spina bifida.

 A portion of the spinal cord or nerves is exposed in a sac through an opening in the spine that may
or may not be covered by the meninges.
 The opening can be closed by surgeons while the baby is in utero or shortly after the baby is born.
 Most people with myelomeningocele have changes in their brain structure, leg weakness, and
bladder and bowel dysfunction.
 Myelomeningocele is often called a snowflake condition because no two people with the condition
are the same.
 Typically, the lower in the spine the opening occurs relates to less symptoms in the person.
 People with myelomeningocele require close follow-up with physicians throughout their childhood
and lifespan to maximize their function and prevent complications such as kidney failure.
Clinical features

 Individuals with MMC often exhibit motor and sensory neurological deficit below the
level of the lesion.
 This may result in lower limb weakness or paralysis that hampers or prevents walking,
and lack of sensation that enhances the risk of pressure sores.
 Urinary and fecal incontinence occur frequently, as does hindbrain herniation (Chiari
II malformation) and associated hydrocephalus which often requires shunting.
 Orthopedic abnormalities including talipes (club foot), contractures, hip dislocation,
scoliosis and kyphosis are frequently observed.
Potential risk factors for neural tube defects

 Maternal nutrition  Other maternal factors

 Alcohol use  Smoking
 Caffeine use  Hyperthermia
 Low folate intake
 Low socio-economic status
 Low dietary quality
 Maternal infections and illnesses
 Elevated glycaemic load or index

 Pregestational insulin-dependent diabetes
Low methionine intake
 Low serum choline level  Pregestational obesity
 Low serum vitamin B12 level  Psychosocial stress
 Low vitamin C level  Valproic acid use
 Low zinc intake
 Environmental factors
 Ambient air pollution
 Disinfectant by-products in drinking water
 Indoor air pollution
 Nitrate-related compounds
 Organic solvents
 Pesticides
 Polycyclic aromatic hydrocarbons
Diagnosis

 Biochemical diagnosis and screening

 elevated concentration of alphafetoprotein (AFP) in amniotic fluid samples
 assay of acetylcholinesterase in amniotic fluid
 Sonographic diagnosis
Management

 The management of MMC traditionally involves surgery within 48 h of birth. The child’s back
is closed to minimize the risk of ascending infection that can result in meningitis.

 Choroid plexus coagulation: the cerebrospinal fluid (CSF)-producing choroid plexus is

coagulated endoscopically to prevent further CSF production, which otherwise exacerbates the
hydrocephalus.
 Ventriculoperitoneal shunt: a shunt is inserted to drain CSF from the brain ventricles into the
peritoneal cavity.
 Ventriculostomy: a small perforation is made in the thinned floor of the third ventricle, allowing
movement of CSF out of the blocked ventricular system and into an adjacent space that is
normally filled with CSF.