Genetical syndromes

1. Genetic syndromes
Autor: Rotari Adrian
dr, șt, med
conf, universitar
Departamentul Pediatrie
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2. Common Genetic Syndromes
• Birth defects and genetic disorders are major
cause of morbidity and mortality in childhood
• 25-40% of children’s hospital admissions
involve genetically or partially genetically
determined conditions
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3. Common Genetic Syndromes – Goals
• Review common genetic syndromes
• Recognize clinical features
• Highlight pathognomonic features
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4. Fetal Alcohol Syndrome
• Small for gestational age
• Mental retardation
• Short nose
• Smooth philtrum
• Thin upper lip
• Short palpebral fissures
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6. Trisomy 21
• Most common chromosomal abnormality
• 1 in 700 live births
• Chromosomal non-disjunction causes 80-90%
of cases
• Robertsonian translocation causes 5%
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7. Trisomy 21 – Clinical Features
• Central hypotonia
• Short stature
• Mental retardation
• Congenital Heart disease
• Structural bowel abnormalities
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9. Trisomy 21 – Clinical Features
• Downslanting palpebral fissures
• Epicanthial folds
• Macroglossia
• Small midface
• Small ears
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10. Trisomy 21 – Clinical Features
• Brushfield spots
• Short broad hands
• Clinodactyly
• Sandal toe
• Single palmar crease
• Lax joints
• Atlanto-axial instabilility
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11. Trisomy 21 – Health Supervision
• From birth to 1 month
–Evaluate for Heart defects/murmur
–CBC
• 1 month to 1 year
–Ophthalmology by 6 months
–BAER by 3 months
–Repeat thyroid function tests
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12. Trisomy 21 – Health Supervision
• 1 to 5 years
– Annual thyroid screening
– Audiogram every 6 months until 3 yrs
– Evaluate for atlanto-axial instability
• C-spine series at 3-5 years
• Repeat before sports participation
• 5 years and above
– Annual CBC and TFT’s
– Annual Ophthomology
– Annual Audiology
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13. Trisomy 18
• Only 5% survive beyond the first year of life
• SGA
• Short sternum
• Overlapping fingers
• Rocker-bottom feet
• Narrow bifrontal diameter
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15. Trisomy 13
• Only 5% of patients live beyond 6 months
• Scalp defects
• Microphthalmia
• Holoprosencephaly
• Cleft lip and palate 60-80%
• Congenital Heart disease in 80%
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17. Trisomy 13
• Clinodactyly
• Missing ribs
• Renal abnormalities
• Post-natal growth retardation
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18. Turner Syndrome
• Monosomy 45,X
• Short stature
• Bicuspid aortic valve or coarctation of the
aorta
• Lymphedema in infancy
• Low hairline, webbed neck
• Horseshoe kidney
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20. Klinefelter Syndrome
• 1 in 1000 live male infants
• 47 XXY
• Hypogonadism with hypospermia
• Increased gonadotropin
• Gynecomastia
• Long limbs
• Mental retardation
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22. DiGeorge Syndrome
• 22q11.2 deletion
• Velocardiofacial Syndrome
• Autosomal dominant
• 60% of patients with TOF and absent
pulmonary valve
• Moderate learning difficulties
• Psychiatric disorders
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23. DiGeorge Syndrome
• C – cardiac anomalies
• A – abnormal facies
• T – thymic aplasia
• C – cleft palate
• H – hypocalcemia
• 22 – 22q11 deletion
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24. DiGeorge Syndrome
• Long tubular nose
• Short philtrum
• Hypertelorism
• Microcephaly
• Cleft lip/palate
• Mild mental retardation
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27. Prader – Willi Syndrome
• Deletion of 15q11
• Missing paternal portion of chromosome
• Hypotonia
• FTT → Hyperphagia
• Small hands and feet
• Mental retardation
• Hypogonadism
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29. Angelman Syndrome
• Deletion of 15q11
• Missing maternal portion of chromosome
• Absent speech
• Mental retardation
• Seizures
• Ataxia
• Inappropriate laughter
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31. Neurofibromatosis
• VonRecklinghausen’s disease
• 1 in 4000
• Defect in NF-1 gene
• NF-2 incidence 1 in 50,000
• Bilateral acoustic neuromas
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32. Neurofibromatosis
• 2 or more of the following:
– > 6 café au lait spots
• > 5 mm in prepubertal
• > 15 mm in post pubertal
– Axillary freckling
– 2 or more Lisch nodules
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34. Neurofibromatosis
• Clinical criteria continued
– 2 or more neurofibromas or 1 plexiform
neurofibroma
– Bony abnormality
• Scoliosis
• Pseudoarthrosis
– Optic glioma
– 1st degree relative with NF-1
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37. Tuberous Sclerosis
• Autosomal dominant
• 1 in 6000
• Mutation in TSC1 at 9p34
• Mutation in TSC2 at 16p13
• Wide clinical spectrum
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38. Tuberous Sclerosis
• Mental retardation
• Seizures
• Calcified tubers in the periventricular area
• Sebaceous adenomas
• Shagreen patches
• Subungual fibromas
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42. Sturge - Weber
• Port wine stain
– Unilateral
– Upper face and eyelid
• Hemiparesis
• Mental retardation
• Focal tonic-clonic seizures
– Contralateral side of nevus
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44. Cri-du-Chat Syndrome
• Deletion of chromosome 5p
• Microcephaly
• Cat like cry in newborn period
• Epicanthial folds
• Severe psychomotor retardation
• Cardiac defects
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46. Cornelia De Lange Syndrome
• Autosomal dominant
• Synophrys, curly eyelashes
• Hirsutism
• Microcephaly, long philtrum
• Hearing loss
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48. In Conclusion
• Wide spectrum of disease
• 40% of idiopathic mental retardation likely
related to chromosomal abnormality
• Advances in genetics research and testing will
identify new clinical syndromes
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49. Bibliografy
• EA; Dahl, RC; Haugsand, TM; Ulvestad, IH; Emilsen, NM; Hansen, B; Cardenas,
YE; Skøld, RO; Thorsen, AT; Davidsen, EM (Feb 5, 2013). "Health and disease in
adults with Down syndrome". Tidsskrift for den Norske Laegeforening : Tidsskrift
for Praktisk Medicin, NY Raekke. 133 (3): 290–94
• Kliegma, Robert M. (2011). "Down Syndrome and Other Abnormalities of
Chromosome Number". Nelson textbook of pediatrics (19th ed.). Philadelphia:
Saunders. pp. Chapter 76.2.
• Hammer, edited by Stephen J. McPhee, Gary D. (2010). "Pathophysiology of
Selected Genetic Diseases". Pathophysiology of disease : an introduction to clinical
medicine (6th ed.). New York: McGraw-Hill Medical.
• Guha, Martin (29 March 2011). "The Gale Encyclopedia of Genetic Disorders (3rd
ed.)2011133Edited by Laurie J. Fundukian. The Gale Encyclopedia of Genetic
Disorders (3rd ed.). Detroit, MI: Gale 2010. ,.
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