common genetic syndromes - usmf · 2020. 3. 21. · common genetic syndromes •birth defects and...
TRANSCRIPT
-
Common Genetic Syndromes
-
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
-
Common Genetic Syndromes – Goals
• Review common genetic syndromes
• Recognize clinical features
• Highlight pathognomonic features
-
Fetal Alcohol Syndrome
• Small for gestational age
• Mental retardation
• Short nose
• Smooth philtrum
• Thin upper lip
• Short palpebral fissures
-
Trisomy 21
• Most common chromosomal abnormality
• 1 in 700 live births
• Chromosomal non-disjunction causes 80-90% of cases
• Robertsonian translocation causes 5%
-
Trisomy 21 – Clinical Features
• Central hypotonia
• Short stature
• Mental retardation
• Congenital Heart disease
• Structural bowel abnormalities
-
Trisomy 21– Clinical features
• Downslanting palpebral fissures
• Epicanthial folds
• Macroglossia
• Small midface
• Small ears
-
Trisomy 21– Clinical Features
• Brushfield spots
• Short broad hands
• Clinodactyly
• Sandal toe
• Single palmar crease
• Lax joints
• Atlanto-axial instabilility
-
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
-
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
-
Trisomy 21 – Health Supervision
• 5 years and above
• Annual CBC and TFT’s
• Annual Ophthomology
• Annual Audiology
-
Trisomy 18
• Only 5% survive beyond the first year of life
• SGA
• Short sternum
• Overlapping fingers
• Rocker-bottom feet
• Narrow bifrontal diameter
-
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%
-
Trisomy 13
• Clinodactyly
• Missing ribs
• Renal abnormalities
• Post-natal growth retardation
-
Turner Syndrome
• Monosomy 45,X
• Short stature
• Bicuspid aortic valve or coarctation of the aorta
• Lymphedema in infancy
• Low hairline, webbed neck
• Horseshoe kidney
-
Klinefelter Syndrome
• 1 in 1000 live male infants
• 47 XXY
• Hypogonadism with hypospermia
• Increased gonadotropin
• Gynecomastia
• Long limbs
• Mental retardation
-
DiGeorge Syndrome
• 22q11.2 deletion
• Velocardiofacial Syndrome
• Autosomal dominant
• 60% of patients with TOF and absent pulmonary valve
• Moderate learning difficulties
• Psychiatric disorders
-
DiGeorge Syndrome
• C – cardiac anomalies
• A – abnormal facies
• T – thymic aplasia
• C – cleft palate
• H – hypocalcemia
• 22 – 22q11 deletion
-
DiGeorge Syndrome
• Long tubular nose
• Short philtrum
• Hypertelorism
• Microcephaly
• Cleft lip/palate
• Mild mental retardation
-
Prader – Willi Syndrome
• Deletion of 15q11
• Missing paternal portion of chromosome
-
Prader-Willi Syndrome
• Hypotonia
• FTT → Hyperphagia
• Small hands and feet
• Mental retardation
• Hypogonadism
-
Angelman Syndrome
• Deletion of 15q11
• Missing maternal portion of chromosome
-
Angelman Syndrome
• Absent speech
• Mental retardation
• Seizures
• Ataxia
• Inappropriate laughter
-
Neurofibromatosis
• VonRecklinghausen’s disease
• 1 in 4000
• Defect in NF-1 gene
• NF-2 incidence 1 in 50,000
• Bilateral acoustic neuromas
-
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
-
Neurofibromatosis
• Clinical criteria continued
• 2 or more neurofibromas or 1 plexiform neurofibroma
• Bony abnormality
• Scoliosis
• Pseudoarthrosis
• Optic glioma
• 1st degree relative with NF-1
-
Tuberous Sclerosis
• Autosomal dominant
• 1 in 6000
• Mutation in TSC1 at 9p34
• Mutation in TSC2 at 16p13
• Wide clinical spectrum
-
Tuberous Sclerosis
• Mental retardation
• Seizures
• Calcified tubers in the periventricular area
• Sebaceous adenomas
• Shagreen patches
• Subungual fibromas
-
Sturge - Weber
• Port wine stain
• Unilateral
• Upper face and eyelid
• Hemiparesis
• Mental retardation
• Focal tonic-clonic seizures
• Contralateral side of nevus
-
Cri-du-Chat Syndrome
• Deletion of chromosome 5p
• Microcephaly
• Cat like cry in newborn period
• Epicanthial folds
• Severe psychomotor retardation
• Cardiac defects
-
Cornelia De Lange Syndrome
• Autosomal dominant
• Synophrys, curly eyelashes
• Hirsutism
• Microcephaly, long philtrum
• Hearing loss
-
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