exam 1 - genetics Flashcards
Genetics and dysmorphology
-Approx 3% of infants born in U.S. have congenital malformations
-Dysmorphology- study of genetic malformations and recognition of patterns that occur in syndromes
-Syndromes- collections of abnormalities (malformations, deformations, dysmorphic features, and abnormal behaviors) that result from a unifying, identifiable etiology
chromosomal disorders: abnormal number: trisomies
-3 copies of a chromosome
-recognizable patterns of facial features, congenital anomalies, and increase in infant/neonatal mortality
-Older children that survive -> cognitive and physical disabilities
-Most trisomic embryos are lost early in pregnancy
-Tx focuses on helping develop to full potential
down syndrome: trisomy 21
-1:700 newborns
-distinctive facial features and generalized hypotonia
-Newborn: feeding problems, constipation, prolonged physiologic jaundice, and transient blood count abnormalities
-Childhood: thyroid dysfunction, visual issues, hearing loss, OSA, celiac disease, and atlanto-occiptal instability
-Increased incidence of transient myeloproliferative disorder and leukemia!!
-Facies: Upslanting palpebral fissures, flat nasal bridge, epicanthal folds, midface hypoplasia, flattened occiput
-Minor limb abnormalities
-Generalized hypotonia!!
-Up to 50% have congenital heart disease (septal defects)- VSD
-GI tract abnormalities: Esophageal/duodenal atresias
edwards syndrome: trisomy 18
-1:3500 newborns
-most spontaneously abort
-severe prenatal and postnatal growth restriction, congenital heart disease, and high rates of neonatal/infant mortality
-profound intellectual disability, feeding dysfunction, and FTT
-Facies: Microcephaly, prominent occiput, small malformed ears, overlapping clenched fingers, and rocker-bottom heels
-SGA, VSD/PDA, undescended testes
patau syndrome: trisomy 13
-1:5000 newborns
-most abort spontaneously in first trimester
-feeding difficulties, FTT, profound intellectual disability
-Dysmorphic features: Scalp cutis aplasia, microcephaly, micropthalmia
-Brain malformations, VSD/PDA, cleft lip/palate, omphalocele, postaxial polydactyly
sex chromosomes abnormalities: Klinefelter syndrome (XXY)
-1:1000 in males
-rarely causes spontaneous abortions
-After puberty: Small testes, gynecomastia, diminished facial/body hair, tall/eunuchoid build, decreased muscle mass
-IQ borderline-normal
-Extra X chromosome > decreased testicular growth > low testosterone > delayed/absent/incomplete puberty, azoospermia, and infertility
-Tx: Testosterone replacement
gene disorders: williams syndrome
-Deletes gene for elastin
-Short stature, congenital heart disease, elfin-like facies (prominent lips), hypercalcemia/uria, developmental delay, neonatal irritability evolving into an overly friendly personality
-Predisposition to HTN and spinal osteoarthritis in adults
-Mild-moderate intellectual deficits
-monitor MSK
gene disorders: DiGeorge syndrome
-Newborns presenting with cyanotic congenital heart disease, thymic hypoplasia, and hypocalcemia
-Microcephaly, hypothyroidism, kidney/cervical spine malformations, palatal clefting, velopharyngeal insufficiency, speech/language delays, congenital heart disease, psychiatric diagnoses (ADHD, anxiety, schizophrenia)
autosomal dominant disorders: neurofibromatosis type 1
-Café au lait spots (> 6 by age 1)
-Neurocutaneous findings by age 8
-Neurofibromas: Benign tumors (Schwann cells, nerve fibers, fibroblasts)
-Large head, scoliosis, developmental/intellectual delays
autosomal dominant disorders: Marfan syndrome
-Mutation in gene for fibrillin-1 (extracellular matrix protein)
-Diagnosis is clinical, based on Ghent criteria
-Facies: Long/thin, down-slanting palpebral fissures, malar flattening, retrognathia
-High-arched palate, crowded dentition
-Positive family history, skeletal abnormalities, lens dislocation
-Scoliosis is progressive
-Astigmatism/myopia
-Motor milestones delayed (joint laxity)
-Adolescents prone to PTX
-Dysrhythmias, aortic/valvular complications sporadically
-Most serious complication is aortic root dilatation -> aneurysmal rupture -> death
-Treatment: Surveillance
-Echocardiogram (serial), B-adrenergic blockade or angiotensin II receptor antagonists to slow rate of aortic root dilatation
autosomal dominant disorders: achondroplasia
-MC form of disproportionate stature
-Short-limbed dwarfism, trident-shaped hands, macrocephaly, mid-face hypoplasia
-Normal intelligence
-Complications: OSA, kyphosis, spinal stenosis
-Treatment: Orthopedic surveillance, adaptive modifications
autosomal dominant disorders: osteogenesis imperfecta
-Brittle bone disease
-Hallmark is fractures with minimal or absent trauma
-Short stature, frequent fractures, bowing of extremities, scoliosis
-Blue sclera, abnormal dentition (brown, translucent teeth), adult-onset hearing loss
-Treatment: Orthopedic, dental, physical/occupational care; bisphosphonates
autosomal dominant disorder: craniosynostosis syndrome
-Group of disorders associated with premature fusion of cranial sutures and an abnormal skull shape (Crouzon syndrome MC)
-Abnormal skull shape, shallow orbits, widely spaced eyes, and midface narrowing
autosomal dominant disorders: cornelia de lange syndrome
-Facies: Hirsutism, medial fusion of eyebrows, and thin/down-turned lips
-Severe growth restriction, upper limb reduction defects, congenital heart disease
autosomal dominant disorders: noonan syndrome
-Short stature, congenital heart disease, and mildly dysmorphic features
-Pulmonary stenosis, and HCMO
-Mild gross motor and speech delay; learning disabilities
autosomal recessive disorders
-Cystic fibrosis
-Smith-Lemli-Opitz Syndrome- Metabolic disorder in the final step of cholesterol biosynthesis pathway > low cholesterol levels and accumulation of precursor (7-dehydrocholesterol)
-Sensorineural Hearing Loss
-spinal muscular atrophy:
-Anterior horn cells in spinal cord degenerate (apoptosis) > progressive atrophy of skeletal muscle
-SMA 0: Prenatal onset, profound hypotonia, respiratory failure at birth
-SMA I: Mild weakness at birth; by 3 months fasciculations and loss of reflexes; by 1 year, eventual respiratory failure
-SMA II: Weakness, decreased reflexes by age 2
-SMA III: Weakening by adolescence
-SMA IV: Weakening by 2nd-3rd decades of life
X-linked disorders (males): duchenne and becker muscular dystrophies
-DMD results from failure of synthesis of muscle cytoskeletal protein dystrophin (less severe form is BMD)
-Elevated serum CK often noted
-Progressive degeneration of skeletal/cardiac muscle occurs
-Proximal muscle weakness and pseudohypertrophy of calf muscles by age 5-6 years; become non-ambulatory by early teens (without early intervention); most die by twenties (respiratory failure/cardiac dysfunction)
X-linked disorders (males): fragile X syndrome
-MC intellectual disability in males
-Intellectual disabilities, oblong facies with large ears, and large testicles after puberty
-Hyperextensible joints, MVP/aortic root dilation
-Hyperactivity, hypotonia, seizures, GI concerns, sleep disorders/scoliosis
x-linked disorders (males): hemophilia A
discuss later
imprinting disorders
all the genes are there but not all are expressed
imprinting disorders: Beckwith-Wiedmann syndrome
-Macrosomia, macroglossia, lateralized overgrowth, omphalocele, embryonal tumors (Wilms tumor), visceromegaly, cytomegaly (adrenal cortex), anterior ear lobe creases/posterior helical ear pits
-Should undergo tumor surveillance protocols (AFP levels, abdominal US)
imprinting disorders: prader-willi syndrome
-Infancy: Severe hypotonia, poor feeding
-Older children (8 years): Hyperphagia/inability to achieve satiety !!!
-Almond-shaped eyes, bitemporal narrowing, small hands and feet
-OSA, hypogonadotropic hypogonadism
-Behavioral rigidity, OCD features
-Treatment: GH is only FDA-approved treatment
teratogens: fetal alcohol syndrome
-Excessive exposure to alcohol during gestation – 30-40% of offspring of mothers whose daily alcohol intake exceeds 3 ounces
-Short stature, poor head growth, developmental delay, and midface hypoplasia (poorly developed philtrum, thin upper lip, narrow palpebral fissures, and short nose with anteverted nares)
-Cardiac, GU, and neural tube defects seen
test
-know what causes these disorders
