Genetic syndromes

Autor: Rotari Adrian

dr, șt, med

conf, universitar

Departamentul Pediatrie

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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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Common Genetic Syndromes – Goals

• Review common genetic syndromes

• Recognize clinical features

• Highlight pathognomonic features

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Fetal Alcohol Syndrome

• Small for gestational age

• Mental retardation

• Short nose

• Smooth philtrum

• Thin upper lip

• Short palpebral fissures

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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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Trisomy 21 – Clinical Features

• Central hypotonia

• Short stature

• Mental retardation

• Congenital Heart disease

• Structural bowel abnormalities

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Trisomy 21 – Clinical Features

• Downslanting palpebral fissures

• Epicanthial folds

• Macroglossia

• Small midface

• Small ears

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Trisomy 21 – Clinical Features

• Brushfield spots

• Short broad hands

• Clinodactyly

• Sandal toe

• Single palmar crease

• Lax joints

• Atlanto-axial instabilility

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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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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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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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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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Trisomy 13

• Clinodactyly

• Missing ribs

• Renal abnormalities

• Post-natal growth retardation

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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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Klinefelter Syndrome

• 1 in 1000 live male infants

• 47 XXY

• Hypogonadism with hypospermia

• Increased gonadotropin

• Gynecomastia

• Long limbs

• Mental retardation

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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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DiGeorge Syndrome

• C – cardiac anomalies

• A – abnormal facies

• T – thymic aplasia

• C – cleft palate

• H – hypocalcemia

• 22 – 22q11 deletion

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DiGeorge Syndrome

• Long tubular nose

• Short philtrum

• Hypertelorism

• Microcephaly

• Cleft lip/palate

• Mild mental retardation

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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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Angelman Syndrome

• Deletion of 15q11

• Missing maternal portion of chromosome

• Absent speech

• Mental retardation

• Seizures

• Ataxia

• Inappropriate laughter

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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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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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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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Tuberous Sclerosis

• Autosomal dominant

• 1 in 6000

• Mutation in TSC1 at 9p34

• Mutation in TSC2 at 16p13

• Wide clinical spectrum

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Tuberous Sclerosis

• Mental retardation

• Seizures

• Calcified tubers in the periventricular area

• Sebaceous adenomas

• Shagreen patches

• Subungual fibromas

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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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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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Cornelia De Lange Syndrome

• Autosomal dominant

• Synophrys, curly eyelashes

• Hirsutism

• Microcephaly, long philtrum

• Hearing loss

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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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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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