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