DOWN SYNDROME

Emily Pollakowski, MD

Background

In 1866, Down described the clinical characteristics we know now as Down Syndrome

In 1959, Lejeune and Jacobs independently discovered trisomy 21 to be the cause

Most common and well known chromosomal abnormality

Most common cause of intellectual disability

Description

Down Syndrome is characterized by mental retardation, dysmorphic facial features, and distinctive phenotypic traits

Classically, hypotonia, flat facies, upslanting pqlpepral fissures, and small ears

Children with Down Syndrome have such a typical look that they look more like each other than their families

Associated Abnormalities: Cardiac Congential heart disease (40-50%, most

not symptomatic at birth) AV canal (60%) VSD ASD PDA Tetralogy of Fallot Aberrant subclavian artery

Associated Abnormalities

Hearing loss (66-75%) Strabismus (33-45%) Nystagmus (15-35%) Refractive errors (50%) Nasolacrimal duct stenosis Delayed tooth eruption

Associated Abnormalities: GI Tracheoesophageal fistula GI atresia (12%) Celiac disease Meckel diverticulum Hirschsprung disease (1%) Imperforate anus

Associated Abnormalities

Renal malformations Hypospadias Cryptorchidism (5-50%) Thyroid disease (15%): congenital

hypothyroidism Neonatal polycythemia Leukemia (1%, 10-30x greater risk than

general population) Retinoblastoma and germ cell tumors

Associated Abnormalities

Obesity Alopecia areata (10-15%) Seizures (5-10%) Alzheimer disease (nearly all over 40

years) Mild to moderate mental retardation (IQ

range 25-70)

Complications

Otitis media with effusion (50-70%) Sinusitis Tonsillar hypertrophy, leading to OSA

(33-75%) Obstructive bowel disease Constipation

Complications

Subluxation of hips Atlantoaxial instability (10-20%, secondary to ligamentous laxity)

Epidemiology

Male > female (1.3:1) 75% of concepti with trisomy 21die in

embryonic or fetal life 85% survive past one year of age Over 50% are expected to live longer

than 50 years Congenital heart disease is most

important factor in determining survival

Frequency

In the United States, frequency is about 1 in 800births Each year, approximately6000 children born with Down Syndrome

Etiology

Full Trisomy 21 (94%) Most common error is maternal

nondisjunction (failure to segregate) at the first meiotic division

Mosaicism ( 2.4%): 2 cell lines present, less severe

Translocation ( 3.3%): 50% de novo, 50% balanced translocation from one parent

Etiology

Advanced maternal age is risk factor for maternal meiotic nondusjunction

At 35 years, risk is 1 in 385 At 40 years, risk is 1 in 106 At 45 years, risk is 1 in 30

Diagnosis

Clinical diagnosis with classic constellation of dysmorphic features

History and physical!

Confirm with karyotype

Karyotype

History

Previous history of infant with Down syndrome in the family

Parental concern about hearing, vision Feeding history: adaquate calories,

vomiting Stooling pattern

History

Development: delay in cognitive abilities, motor or language development, social competence

Cardiac history:fainting episodes, palpitations

Symptoms of sleep apnea: snoring, daytime somnolence, behavioral changes, and school problems

History

Symptoms of atlantoaxial instability: easy fatigability neck pain, limited neck mobility or head

tilt, torticollis difficulty walking, change in gait pattern loss of motor skills, incoordination sensory deficits spasticity, hyperreflexia

Physical

General-Short stature-Hypotonia (80-100%), with open mouth and protruding tongue-Midface hypoplasia

Physical

Head-Brachycephaly with flattened occiput-Microcephaly Eyes-Upslanting palpepral fissures (98%)-Inner epicanthal folds-Brushfield spots (speckled iris)

Physical

Ears-Small, prominent, low set, overfolding of

helix, small canals Nose-Small (85%), flat nasal bridge

Physical

Tongue-Relative but not true macroglossia Mouth-High arched palate Teeth-Missing (50%)-Small, hypoplastic

Physical

Heart-Assess for murmur, arrthymia Abdomen-Look for distension in neonate (rule out

obstruction)-Diastasis recti GU-In males, small penis and cryptorchidism

Physical

Extremities-Broad hands, with short metacarpals-Single transverse palmar crease (50%)-5th finger with hypoplasia of midphalanx

and clinodactyly (60%)-Wide gap between 1st and 2nd toes-Hyperflexibility of joints Skin-Fine, soft, sparse hair

Next steps

Genetic counseling recommended History of Down Syndrome increased risk

of recurrence (1%) Affected individuals rarely reproduce Only 15-30% females are fertile Males are infertile

Monitoring

Routine vaccinations Medications Growth and development:-Specific growth charts available-Average age of meeting developmental

milestones differs from general population

Monitoring

Cardiac-Early evaluation and follow-up for

congenital heart disease-Endocarditis prophylaxis for certain

lesions Endocrine-Thyroid function tests as newborn to rule

out hypothryoidism, with follow-up

Monitoring

Ophthalmologic-Early evaluation for cataracts and

glaucoma Ear, nose, throat-Periodic audiologic exams Orthopedic-Screen for atlantoaxial instability with

radiography

Monitoring

Psychiatric/Social:-Screen for depression or anxiety-Manage behavioral problems-Social support-Family support-Long term living arrangements

Prognosis

Overall outlook dramatically improved However, overall life expectancy

reduced Importance of empowering and

supporting families as best we can