Pediatrics (Exam 1) - Genetic Disorders

marfan syndrome inheritance

autosomal dominant

3 systems involved in marfan syndrome

skeletal, opthalmologic, cardiac

Caused by a pathologic variant in a single gene, FBN1 (a connective tissue protein gene)

marfan syndrome

Marfan's Syndrome (Ophthalmologic):

-Early and severe _______

-Dislocation of the ______

-Hypoplastic _____

-Increased risk of retinal ________

myopia, lens, iris, detachment

Marfan's Syndrome (Cardiac):

-_______ insufficiency

-Progressive ________ of the aortic root

aortic, dilation

Marfan's Syndrome (Skeletal):

•Tall, thin body habitus

•_________ fingers and toes

•________ excavatum or carinatum

•Scoliosis

•Pes _______

•Joint __________

long, pectus, planus, laxity

Ghent criteria used for diagnosis of Marfan’s:

-Positive _______ history + __ other characteristic

OR

-Systemic score ≥ ____ points

family, 1, 7

Marfan syndrome scoring:

•Relates to wrist/thumb _______

•Elbow ________

•Pectus deformity

•Arm ________

•Spinal deformity

•________ characteristics

•Significant _______

•Mitral valve ___________

flexibility, extension, span, facial, myopia, prolapse

neurofibromatosis inheritance pattern

autosomal dominant

Spontaneous mutations account for 30-50% of cases caused by a pathologic mutation in the, NF1 gene (neurofibromin protein, a tumor suppressor gene)

neurofibromatosis

Also known as von Recklinghausen disease

neurofibromatosis

Life expectancy for patients with NF1 may be reduced by _________

10-15yrs

S/Sx:

•Café au lait macules

•Axillary freckling

•Cutaneous neurofibromas

•Lisch nodules

neurofibromatosis

Concerning if there are more than _____ Café au lait macules that are >____ mm in diameter in a prepubertal child

6, 5

•Small discreet soft lesions within the dermis and epidermis

•Usually asymptomatic

•Mostly cosmetic concerns

cutaneous neurofibromas

distinctive for neurofibromatosis, iris hamartomas; benign, disappear in adulthood

lisch nodules

MCC of death in neurofibromatosis

malignancy

Complications

Learning disabilities

Scoliosis

Seizures

Cerebral vascular abnormalities

Other tumors, such as optic nerve gliomas

neurofibromatosis

47, XX, + 21 or 47, XY, + 21

trisomy 21 (down syndrome)

Most common chromosomal abnormality in liveborn infants

trisomy 21 (down syndrome)

Trisomy 21 (Down syndrome):

•95% due to _____________

•3% due to Robertsonian ___________ (merger of 2 chromosomes, often 13, 14, 15, 21, 22)

•2% due to ____________

nondisjunction, translocations, mosaicism

Downs syndrome pts are at higher risk for :

•Congenital heart disease (40%), ie: _______

•Hypothyroidism

•Atlantoaxial instability

•Higher rate of ________

•Polycythemia

•Increased risk for ________

•Cataracts

•GI anomalies, ie: __________

•Increased risk of _________ by age 35 y/o

vsd, infection, ALL, hirschsprung, alzheimer's

Recognizable characteristics in the neonatal period

•Facial features

•Hypotonia

•Short broad hands

•Single transverse palmar crease

•Wide gap between the first and second toes

trisomy 21 (down syndrome)

down syndrome appearance:

•__________: Flattened occiput

•__________ midface

•__________ nasal bridge

•________ ear with over-folded helix

•Neck folds due to _________ skin

brachycephaly, hypoplastic, flattened, small, redundant

down syndrome appearance:

•Upslanting palpebral ________

•____________ folds

•Open mouth with _________ tongue

fissures, epicanthal, protruding

47, XX, + 18 or 47, XY, + 18

trisomy 18

Also called Edward's syndrome

trisomy 18

2nd most common autosomal trisomy

trisomy 18

Trisomy 13 and 18:

•Male : Female = _____ who survive

•Only 12% reach the ____ birthday

•_______ for gestational age

1:4, first, small

trisomy 18 is caused by _______________

nondisjunction

S/Sx:

•Hypertonia

•Prominent occiput

•Micrognathia

•Low-set, malformed ears

•Short sternum

•Rocker bottom feet

•Hypoplastic nails

•2nd and 5th digits overlap the 3rd and 4th in clenched fists

trisomy 18

47, XX, + 13 or 47, XY, + 13

trisomy 13

Also called Patau's syndrome

trisomy 13

3rd most common trisomy

trisomy 13

Caused by nondisjunction or Robertsonian translocations (chromosomes 13 and 14)

trisomy 13

S/Sx:

•Midline facial defects (cleft lip/palate)

•Midline central nervous system anomalies

•Sloping forehead

•Small, low-set, malformed ears

•Polydactyly

•Genital deformities

•Congenital heart disease

•aplasia cutis congenita

trisomy 13

Punched out scalp lesion over the occiput pathognomonic for trisomy 13

aplasia cutis congenita

Most common genetic cause of hypogonadism and infertility in men

klinefelter syndrome

47, XXY or 46, XY (if mosaicism)

klinefelter syndrome

Extra X chromosome and poor sperm viability causes infertility with no physical evidence in infancy or childhood

klinefelter syndrome

S/Sx:

Males are phenotypically normal until adolescence

In adolescence

•Genitals remain infantile in size

•Failure to develop facial hair, deep voice, and libido

In adulthood

•Gynecomastia may develop

•Tall, long limbs

•Osteopenia

•Osteoporosis

klinefelter syndrome

-Sex chromosome abnormality

-45, X --> women

-Nondisjunction , post-conceptional

turner syndrome

The only monosomy that survives to birth

turner syndrome

Responsible for up to 10% of first trimester losses of pregnancy

turner syndrome

S/Sx:

•Low set ears

•Triangular face

•Flattened nasal bridge

•Epicanthal folds

•Webbing of the neck

•Shield-like chest; wide internipple distance

•Puffy hands and feet

turner syndrome

S/Sx:

•Congenital heart defects

•horseshoe kidney

•Short stature

•Hypothyroidism

•Infertility

•streak gonads and estrogen deficiency

turner syndrome

Turner syndrome may be diagnosed in:

•Infancy, if _________ is more evident

•Childhood, due to _______ stature

•Adolescence, due to failure to develop _________ sexual characteristics

•Adulthood, due to __________

phenotype, short, secondary, infertility

Paternal uniparental disomy

angelman syndrome

Caused by Chromosome Deletion in maternal chromosome 15 in the 15q11 region

angelman syndrome

•Partner to Prader-Willi Syndrome (opposite deletion)

•Both result in moderate to severe intellectual disability

•Both begin with failure to thrive

angelman syndrome

S/Sx:

•Absence of speech

•Ataxic movements of the arms and legs

•Short stature

•infertile

•Maxillary hypoplasia

•Microbrachycephaly

•Seizure disorder with inappropriate laughter

angelman syndrome

Maternal uniparental disomy

prader willi syndrome

Caused by Chromosome Deletion in paternal chromosome 15 in the 15q11 region

prader willi syndrome

S/Sx:

•Fetal and infantile hypotonia

•Poor initial weight gain, feeding concerns

•Postnatal obesity with insatiable appetite

•Developmental delay

•Almond-shaped eyes

•Hypogonadism

•Small hands and feet

prader willi syndrome

Failed expression of FMRP (the protein product of the FMR1 gene)

fragile X syndrome

Most common cause of inherited intellectual disability

fragile X syndrome

Fragile X syndrome Affects _____ and ___________ development in the early embryonic period.

CNS, testes/ovary

S/Sx:

•Macrocephaly

•Long, wide, protruding ears

•Long face

•Prominent jaw

•Flattened nasal bridge

•Velvety skin

•Hyperextensible joints

•Mitral valve prolapse

•Macro-orchidism

fragile X syndrome

S/Sx:

•Learning disabilities

•Physical features less common

•Mood disorders

•Schizoid personality

•Disturbances of affect, socialization, communication

fragile X syndrome in females

S/Sx:

•Severe-borderline cognitive impairment

•Delayed speech

•Short attention span

•Hyperactivity

fragile X syndrome in males

Deletion in the short arm of chromosome 5

cri du chat

S/Sx:

•Catlike cry due to tracheal hypoplasia

•Low birth weight

•Failure to thrive

•Hypotonia

•Developmental delays

•Microcephaly

•Craniofacial dysmorphism

cri du chat

Deletion in chromosome 7

williams syndrome

S/Sx:

•Supravalvular aortic stenosis

•Growth delay and short stature

•Moderate intellectual disability but strong personal social skills—gregarious personality

•Potential for autism spectrum disorder and unusual musical ability

•Hypercalcemia

williams syndrome

S/Sx:

"Elfin facies"

•Flared eyebrows

•Blue irides

•Full periorbital and oral regions

•Depressed nasal bridge

williams syndrome

Most common cause of preventable intellectual disability

fetal alcohol syndrome

S/Sx:

•In utero and post natal growth restriction

•Microcephaly

•Intellectual disability

•Dysmorphic facial appearance

•Skeletal and cardiac abnormalities

fetal alcohol syndrome

S/Sx:

•Problems with coordination

•Attention deficit

•Hyperactivity

•Impulsivity

•Learning disorders

•Behavior disorders

fetal alcohol syndrome