COMMON CONGENITAL SYNDROMES

1. COMMON CONGENITAL SYNDROMES Unit 1 Module 3

2. THE DYSMORPHIC CHILD 3/100 infants are born with a congenital defect Many of them associated with a degree of developmental disability Genetic disorders and birth defects account for > 40% of childhood deaths Diagnosis of syndromes is based on pattern of dysmorphic features and organ involvement

3. APPROACH TO EVALUATING THE DYSMORPHIC CHILD History Prenatal/obstetrical history Complete 3 generation family pedigree: - Consanguinity - Stillbirths - Neonatal deaths - Specific congenital defects/illnesses - Mental retardation (MR) - Multiple miscarriages - Ethnicity

4. APPROACH TO EVALUATING THE DYSMORPHIC CHILD Physical Examination - Growth parameters: head circumference (HC), height (Ht), and weight (Wt) - Skull: contour and symmetry - Hair: texture and pattern - Neck: look for redundant nuchal skin/webbed neck - Facial features: compare with siblings and parents - Ears: structure, size, placement and rotation

5. APPROACH TO EVALUATING THE DYSMORPHIC CHILD Physical Examination - Eyes -distance apart, orientation, eyebrows and eyelashes, any unusual folds or creases, coloboma, fundus - Nose: nasal bridge, nostrils - Philtrum: length and shape - Mouth: lips, palate, tongue and teeth - Chin: size and position

6. APPROACH TO EVALUATING THE DYSMORPHIC CHILD Physical Examination - Thorax: shape, size and nipple spacing - Hands and feet: creases, structure (e.g. overlapping fingers/toes), and nails - Limbs: proportions, reduction defects, and amputations - Spine: scoliosis - Genitalia: ambiguous - Skin: hair tufts, sacral dimples/sinus

7. APPROACH TO EVALUATING THE DYSMORPHIC CHILD Management - Refer for investigations - X-rays if bony abnormalities or if suspect a congenital infection - Genetic/chromosome studies - Biochemistry: specific enzyme assays - Molecular biology for specific testing - Counseling and recurrence risk assessment

10. Jarvis, Carolyn, Physical Examination and Health Assessment, 1992 edition, Pg 303Jarvis, Carolyn, Physical Examination and Health Assessment, 1992 edition, Pg 303

11. DOWN SYNDROME (DS) Most common abnormality of autosomal chromosomes Trisomy 21 Incidence- 1 in 600-800 live births Incidence rises with advanced maternal age to 1 in 20 by age 45 years Affected fetuses have increased risk or spontaneous abortion

12. DOWN SYNDROME (DS) Clinical Features - Very wide range of severity - Low IQ - Developmental delay - Short stature - Obesity - Shorter life expectancy

13. DOWN SYNDROME (DS) HEENT Features - Flat occiput, 3rd fontanelle, - Microcephaly, small midface, - Small mandible and maxillae - Upslanting palpebral fissures - Epicanthal folds - Speckled iris (Brushfield spots)

14. DOWN SYNDROME (DS) HEENT Features - Refractive errors and strabismus Furrowed prominent tongue High arched palate - Ear anomalies - Frequent AOM - Hearing problems

15. DOWN SYNDROME (DS) CVS: - Congenital heart defects (50%), particularly septal defects (VSD) GIT: - Duodenal/esophageal/anal atresia - TE fistula - Hirschsprung disease - Chronic constipation

16. DOWN SYNDROME (DS) MSK: - Lax joints including dysplastic hips - Vertebral anomalies - Atlantoaxial instability - Wide gap between 1st and 2nd toes GU: - Cryptorchidism

17. DOWN SYNDROME (DS) Dermatology: - Simian (palmar) crease - Abnormal dermatoglyphics Hematology: - 1% lifetime risk of leukemia Endocrine: - Hypothyroidism

18. DOWN SYNDROME Management- symptomatic as needed care Recommended testing - ECHO - Thyroid tests - Atlanto-occipital x-ray at 2 and 12 years (controversial) - Hearing test - Ophthlamology assessment Early intervention stimulation programs to help child reach full potential

19. TURNER SYNDROME Genotype: 45X (most common), mosaic (45XO) Incidence: 1:2500 live female births Clinical features - Intelligence usually normal, may have mild learning disabilities - Short stature, short webbed neck - Low posterior hair line, wide carrying angle at elbows - Broad chest, widely spaced nipples - Lymphedema, cystic hygroma in the newborn - Polyhydramnios, lung hypoplasia

20. TURNER SYNDROME Clinical features ( continued) - Gonadal dysgenesis ---> infertility, primary amenorrhea, - Lack of development of secondary sexual characteristics - Coarctation of the aorta, bicuspid aortic valve - Renal anomalies - Increased risk of hypertension (HTN)

21. TURNER SYNDROME Prognosis: Normal life expectancy if no complications Management - Early screening for cardiac disease - Growth hormone therapy for short stature - Estrogen replacement at time of puberty

22. KLINEFELTER SYNDROME Genotype: 47 XXY (most common) Incidence: 1:1000 live male births Associated with late maternal age Developmental delay, mild mental retardation, long limbs Hypogonadism, hypospermia Gynecomastia, lack of facial hair Treatment: testosterone in adolescence

23. FRAGILE X Most common genetic cause of developmental delay in boys Incidence 1:1250; X-linked recessive Clinical features - Overgrowth: prominent jaw, forehead, ears; elongated, narrow face - Macroorchidism - Hyperextensibility - High arched palate - Mitral valve prolapse

24. FRAGILE X Often hyperactive and/or autistic IQ typically 30-65 but 20% of affected males have normal intelligence Diagnosis - Genetic studies: Female carriers may show some intellectual impairment Female carriers may show some intellectual impairment

25. DIGEORGE SYNDROME 2nd most common genetic diagnosis (next to Down syndrome) Results from microdeletions of 22q11 (unequal crossing of chromosomes in meiosis) Presents in newborn period

26. DIGEORGE SYNDROME Clinical features: "CATCH 22" - Cyanotic CHD Anomalies in face: craniofacial anomalies Thymic hypoplasia ? immunodeficiency, recurrent infections Cognitive impairment Hypoparathyroidism ? hypocalcemia 22q11 microdeletion Less severe phenotypes of 22q11 deletions present later in childhoodLess severe phenotypes of 22q11 deletions present later in childhood