CSN Vittal

CSN Vittal

History

First described by John Langdon Down,

1866

Trisomy 21 described by Professor

Jérôme Lejeune & Turpin in 1959

In 1975, NIH suggested that possessive

use of eponym should be discontinued

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Incidence

1 in 700 - 800 births

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Aetiology

95 % meiotic non-disjunction

4 % Robertsonian translocation

(from Chr 14 or 21 / 22)

1% due to mitotic non-disjunction with

mosaicism In 75 % of cases extra chromosome is of

maternal origin

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Nondisjunction

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Robertsonian translocation

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Mosaicism

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Karyotype

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Advanced maternal age

Maternal Age Risk of Down Syndrome

15 – 29 yrs 1 : 1500

30 – 34 yrs 1 : 800

35 – 39 yrs 1 : 270

40 – 45 yrs 1 : 100

45 and above 1 : 50

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Advanced maternal age

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Clinical Features Hair : Sparse, soft, wooly

Head : Microcephaly, brachycephaly, wide AF

Face : Flat face, mid facial hypoplasia, flattened

nasal bridge, dysplastic pinnae

Tongue : Furrowed, protruding scrotal tongue,

Nose : Pug nosed (cartilaginous part wide and triangular) Ears: Low set, funnel shaped, lop ears, conductive hearing loss –

middle ear disease Oral Cavity: High arched palate, Neck : Short with pterygium coli

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Clinical Features - Eyes: Upslanting, myopia, hypermetropia strabismus, Brushfield spots, Cataracts : Y – Suture, arctuate,

numerous flakes glaucoma Keratoconus, blepharitis Interpupilary distance

increased Medial epicanthal folds Hypertelorism Nystagmus

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Clinical Features Chest: CVS Defects: 40-60%

43 % AV Canal defects, 10% Ostium primum ASD, 32 % VSD, PDA, 6% Fallot’s tetrology

Skin: Roughened or hyperelastic / Norwegian scabies

EndocrineThyroid: hypothyroidism in 30%Pituitory tumorsBoys - sterile

GI : TEF, duodenal atresia, omphalocele, annular pancrease, microcolon, anorectal anomalies, Meckel’s diverticulam, aganglionic megacolon

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Clinical Features Extremities –

Upper Limb: ○ Short and stumpy fingers (Brachydactyly), Clinodactyly, ○ Simian crease (Siegert sign)

Lower limb: Distance between first and 2nd toe increased Kennedy crease – Deep vertical crease in between

first and second toes

Acetabula are shallow- flattened lower edges Ribs: Absence of one pair, 12th rib anomalies

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Clinical Features

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Dermatoglyphics

Ulnar loops in most digits Radial loops in fingers 4 and 5 Distal axial triradius or large ATD angle Arch tibial or small loop distal in hallucal

area Simian crease, single crease on finger 5

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Dermatoglyphics

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Clinical Features Musculoskeletal:

Hypotonia with flabby musclesHyperextensible jointsAtlanto axial dislocation

HematologicalALL – 97 fold increased riskMyeloproliferative disodersThrombocytopeniaJuvenile chronic myeloid leukemiaMacrocytosis

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Clinical Features

Simian Sydney

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Clinical Features CNS

West syndrome Moderate to severe MREpilepsy in 5 – 10 %Alzheimer’s like syndrome

Immune SystemCellular immune disordersIgM levels decreasedProne for viral UR infection

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Popular Down Syndrome Stereotype

Happy

Affectionate

Pleasant and

Music loving

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D/D

Cretinism Fragile X syndrome

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Investigations

U/s – Double bubble Echo - AV canal defects X- Ray – Short femur or humerus Echogenic small bowel

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Screening

1. Serum -fetoprotein - Decreased

2. Unconjugated estradiol level - Decreased

3. Human chorionic gonadotrophin - Incresed

Triple Test – 65% detection rate

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Diagnosis

1. Serum -fetoprotein - Decreased

2. Unconjugated estradiol level - Decreased

3. Human chorionic gonadotrophin - Incresed

+4. Inhibin A - Incresed

Quadruple Test - 75% detection rate

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Diagnosis

1. This test measures the alpha feto protein, produced by the fetus, and

2. free beta hCG, produced by the placenta.

AFP / free beta screen - 80% detection rate

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Diagnosis

1. Thickened nuchal fold

2. Absent nasal bone

3. Short femur

4. Cardiac or GI anomalies

U/S. Abdomen

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Diagnosis

Uses ultrasound to measure Nuchal Translucency in addition to the

Free Beta hCG and PAPPA (pregnancy-associated plasma

protein A).

NIH has confirmed that this first trimester test is more accurate than second trimester screening methods.

Nuchal translucency / free beta / PAPPA screen: 91% detection rate

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Screening – 1st Trimester

Maternal serum PAPP – A Increased

Maternal free hCG Increased

Fetal nuchal translucenceny thickness

> 4 mm (USG)

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Screening – 2nd Trimester

AFP Decrease

hCG Increase

E 3 Decrease

Inhibin A Increase

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Diagnosis

1. Only 11 ribs

2. 2 to 3 ossification centres for manubrium

3. Hypoplasia of skull and facial bones, middle phalanx of little finger

4. Accessory epiphyses for 2nd metacarpal

5. Coxa valga

6. Pelvis – ilia are broad and flaring, acetabular and iliac angles are reduced

X- Ray

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Diagnosis

The sum of both the acetaular and both iliac angles divided by two:

Normal = 81 In Down syndrome = < 60

Iliac Index in 2nd trimester – (80% accuracy)

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Down syndrome diagnosis - overview

1st Trimester

• PAPPA • HCG • Nu Thickness

85%

2nd Trimester

• MS AFP • E 3 • b HCG

•INHIBIN

60%76%

Integrated Tests94%

NasaL Bone absent : 1st trimester

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Management Antioxidants like Zn – Alzheimer’s disease AEDs – for epilepsy CVS / GI Abnormalities : Corrective surgeries Refractory errors : Appropriate lenses Speech & Language Defects: Specialist speech

therapies Anemia: Appropriate nutrients Hypothyroidism : Thyroxine Skin disorders : Moisteners, appropriate therapies Low cholesterol diet Immune deficiencies: Vitamin C and Antibiotics

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Risk of Recurrence

Robertsonian Translocation 21 – 13, 14, 15Female carrier : 15%Male carrier : 5%

Robertsonian Translocation 21 – 22Female carrier : 10%Male carrier : 2%

Robertsonian Translocation 21 – 21Female or Male : 100%

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Management

Karyotype testing, if not already done Hearing tests, which may be done at birth or by

3 months of age. A complete blood count (CBC).

Check for signs of leukemia. A blood test to check for thyroid problems

(usually hypothyroidism). A complete heart evaluation

About 40% to 50% of babies with Down syndrome have heart defects.

Birth to 1 mo.

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Management

Ear problems. 50% to 70% risk for ear problems - otitis media with effusion A special hearing test (behavioral audiogram) should be given

at 1 year of age. The Down Syndrome Medical Interest Group (DSMIG) recommends another hearing evaluation at 6 months of age

Eye problems. Strabismus, cataracts, and nystagmus by 6 months of age.

Thyroid function. at 6 months and 12 months (and annually after 1 year of age).

Growth and weight gain. Immunizations.

1 mo. To 1 year

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Management

X-rays to evaluate bones in the neck Dislocation of the neck bones (atlantoaxial dislocation). between

ages 3 and 5 to look for signs of loose ligaments that may lead

to dislocation. These may be done only once.

Additional X-rays – if child wants to participate in Special Olympics or

if symptoms such as neck soreness.

Early Childhood (1 to 5 yrs)

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Management

Skin problems. Extreme dryness, acne, or other problems may

develop during puberty that can get worse if they are not recognized and treated.

Sleep apnea. You may be asked questions about your child's

sleeping habits, such as whether he or she snores or is restless.

Middle and Late Childhood (5 to 13 yrs)

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Management

Skin problems. Thyroid function. Hearing problems. Eye problems. A teenager or adult should

have a thorough eye exam every year.

Adolescence (13 to 21 yrs)

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Management

Symptoms of sleep apnea. Behavioral changes or signs of mental health problems. Dementia. Weight gain and signs of obesity. Heart problems, such as mitral valve prolapse or aortic

valve regurgitation. Problems with the reproductive organs. Women will have yearly breast exams. Should be screened for thyroid problems every year. Hearing should be tested every 1 to 2 years. Should have a thorough eye exam every year

Adulthood

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Skill Development

Walking and other motor development milestones. Help your baby and young child strengthen

muscles through directed play.Exercise program to help your child maintain

and increase muscle strength and physical skills.

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Skill Development

Self-feeding. You can help your child learn to eat

independently by sitting down together at meals.

Use gradual steps to teach your child how to eat, starting with allowing the child to eat with his or her fingers and offering thick liquids to drink.

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Skill Development

Dressing. Teach your child how to dress himself or

herself by taking extra time to explain and practice.

Communicating. Simple measures, such as looking at

your baby while speaking or showing and naming objects, can help your baby learn to talk.

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Skill Development

Grooming and hygiene. Help your child learn the importance of

being clean and looking his or her best.Establish a daily routine for bathing and

getting ready. Gradually add new tasks to the routine,

such as putting on deodorant.

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Often different types of therapy, such as speech therapy, can help children with

Down syndrome learn necessary skills. These therapies are used throughout life, even during adulthood. The specifics change as your child grows and develops.

Be aware of his or her vulnerabilities and potential social problems. Although your child can overcome

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Life Expectations

The typical life expectancy of people with Down syndrome has nearly doubled in recent decades, from 25 years in 1983 to 49 years in 1997

About 13% of people with Down syndrome live longer than 68 years

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System wise problems in Down’sNeuropsychiatric MR

Alzheimer like disease after 25 yrs Autistic behaviour

CVS CHD 40% - AV cushion defects before 10 mo. Cor pulmonale due to nasopharyngeal obstruction due to tonsillitis / adenoiditis, hypotonia of pharyngeal muscles, maldevelopment of upper airways

GIT Atresia of gut ( 8% newborns with Duodenal atresia) Hirschprung’s disease

Otological Impaired hearing (60-70% due to middle ear effusion) Wax ( because auditory canal is narrow)

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System wise problems in Down’sOcular Congenital cataracts 1% ( correct before 3 mo.)

Nystagmus (5-30%) Strabismus (23-44%) Blepharitis (2-67%) Refractoconus (5-8%) Refractive Errors (70-80%) Tear duct stenosis Cataract after 25 yrs (12-86%)

Immune system

Frequent infections Hepatitis B Autoimmune diseases Celiac disease Trace element deficiency

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System wise problems in Down’sEndocrine Congenital hypothyroidism 1%

Thyroid antibodies Hypo or hyperthyroidism Growth retardation – (selective def. of insulin like growth factor 1 - result of hypothalamic dysfunction) Girls fertile – boys sterile

Orthopedic Muscle hypotonia Joint laxity Dislocation of patella and hip Epiphysiolysis of hip Hallus valgus Atlantoaxial dislocation ( 10% radilolgically)

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Than Q - Vittal