Genetic syndromes Flashcards
Dysostosis multiplex, flattened midline face, wide nasal bridge, organomegaly, corneal clouding
Hurlur syndrome (Severe Mucopolysaccharidosis type I)
Fibrous dysplasia
McCune-Albright Syndrome
Capillary malformation (port-wine stain)
Sturge-Weber Syndrome
Sturge-Weber Syndrome findings
Seizures, choroidal vascular malformation, cutaneous capillary malformation/port wine stain, glaucoma, imaging = unilateral serpiginous parenchymal calcifications associated with hemispheric atrophy
Neurofibromatosis 1 diagnostic criteria
> = 2 of following: axillary freckling; >= 6 large cafe au lait spots; hamartomas in iris (Lisch nodules); >= 1 neurofibroma; osseous lesions (sphenoid dysplasia/long bone abn/pseudoarthrosis); optic glioma; 1st degree relative with NF1
Neurofibromatosis 1 imaging findings
Hyperintense areas in basal ganglia and cerebellum (areas of dysmyelination => cognitive, perceptual, executive, and attention deficit)
Multiple cortical and periventricular calcific deposits
Tuberous sclerosis
Unilateral serpiginous parenchymal calcifications associated with hemispheric atrophy
Sturge-Weber syndrome
Obliteration of the cerebral ventricles associated with loss of gray-white matter differentiation
Cerebral edema
Beckwith-Wiedemann syndrome
Macrosomia (height and weight), hemihypertrophy, macroglossia, Wilm’s tumor (HTN, mass, and microscopic hematuria), hypoglycemia (Pancreatic beta cell hyperplasia), abdominal wall defects (omphalocele, diastasis recti, umbilical hernia)
Kostmann syndrome
Prolonged neutropenia and no bone marrow reserves due to myeloid arrest (insensitive to G-CSF)
Smith-Lemli-Opitz syndrome (SLOS)
Path: Deficiency of 7-dehydrocholesterol reductase => increase plasma 7-dehydrocholesterol. Clx: Syndactyly of 2nd and 3rd toes, microcephaly with narrow bifrontal diameter, broad nasal tip with anteverted nares, hypertelorism and ptosis, cleft palate, micrognathia, and low-set ears. Genetics: AR
Zellweger syndrome
Path: Disorder of peroxisomes. Clx: Large anterior fontanelle, high forehead, epicathal folds, cataracts, broad nasal bridge, jaundice (hepatic dysfunction), epiphyseal stippling, renal dysfunction. Genetics: AR
Menkes disease
Path: Impaired copper uptake (low copper and ceruloplasmin). Clx: Full cheeks with sagging jowls and lips, fragile and hypopigmented hair and eye brows, neurogenic degeneration at 2-3 months of age. Genetics: X-linked
Stickler syndrome
Connective tissue d/o. Midfacial hypoplasia, cleft palate, Pierre robin, hearing loss, eye disease (bad myopia, cataract, retinal detachment)
Allgrove or triple-A-syndrome
Achalasia, Alacrima (absent/reduced tears), and Adrenocorticotropic hormone-resistant Adrenal insufficiency (Other sxs: autonomic dysfunction, ID, DD, dysarthria, SN neuropathies)
Trisomy 18 (Edward’s syndrome)
Overlapping fingers and hypoplastic nails, rocker bottom feet, cardiac/renal defects, central apnea
Rett syndrome
Path: X-linked or de novo mutation MECP2 gene; Clx: male die after birth, female have normal perinatal period => language and motor delay with regression, and seizures (~80%), onset around 6-18 months, live to 20s-30s.
4 yo girl, webbed neck, hypertelorism, pulmonic ejection click and systolic ejection murmur.
Noonan syndrome. Karyotype 46,XX or 46,XY. Developmental delay, short stature, heart defect (pulmonary valvular stenosis). Similar to Turner except can happen in boys, has pulmonary stenosis as opposed to aortic malformations, and hypertelorism
Klippel-Feil syndrome
Clx: Congenital fused cervical vertebrae (short neck, limited ROM, low hairline at back of head), Sprengel deformity (failure of scapula to descend), atlantoaxial instability, hemivertebrae, scoliosis.
Williams syndrome
Clx: Extremely friendly with strangers, elfin-like face (strabismus, peg-like teeth, wide set eyes, upturned nose, large philtrum, pointed chin), low IQ, supravalvular aortic stenosis, hypercalcemia
McCune-Albright Syndrome
Triad of 1) Polyostotic fibrous dysplasia, 2) Cafe au lait spots, 3) precocious puberty. Gain of function mutation for G-protein receptors of hormones (ACTH, TSH, GnRH)
Painless rectal bleeding and hyperpigmented macules on lips
Peutz-Jeghers syndrome - AR disease with colonic hamartomatous polyps, increase risk cancers
Nail Patella syndrome
LMX1B gene mutation => Limb and renal effects => hypoplastic nail, patellar dislocations, iliac horns, and proteinura (can get ESRD)
Nail Patella syndrome
LMX1B gene mutation => Limb and renal effects => hypoplastic nail, patellar dislocations, iliac horns, and proteinura (can get ESRD)
Bloom Syndrome
AR mutation BLM gene (DNA helicase). Clx: photosensitivity, telangiectasia, inc. cancer, low immunoglobulin (inc. infection), bird like faces
Patau syndrome (Trisomy 13)
Defect in development of prechordial mesoderm => MIDLINE DEFECTS => defect in midface, eyes, forebrain => omphalocele, rocker bottle feet, polydactyly (as opposed to overlying fingers in Edwards), CHD, and aplasia cutis congenita
Turner syndrome associated disorders
Cubitus valgus, extremity edema at birth => hyperconvex fingernails, Cardiac (bicuspid AV, CoA), renal (horseshoe, duct abn), bone (scoliosis, Madelung deformity), metabolic (dyslipid, diabetes), autoimmune (celiac, thyroid)
Brushfield spots
Whitish spots in ringlike configuration around periphery of iris, associated with trisomy 21 esp blue eyes
Septooptic dysplasia (SOD)
Absense of optic chiasm/nerve, agenesis of septum pellucidum, midfacial anomalies, microphalus/penis
Job syndrome
Autosomal dominant hyper-IgE syndrome. Path => defect in Th17 cells => neutrophils fail to get to tissue sites despite chemotactic chemokines => recruit eosinophils instead => secrete IgE (cause eczema). Clx: FATED => Facies coarse, Abscess (staph), Teeth (2 rows of teeth or retain primary teeth), E (high IgE), Derm (eczema).
Denys-Drash syndrome
Wilms tumor, nephropathy, ambiguous genitalia
Hearing loss, white forelock, premature graying, telecanthus, iris heterochromia, hyper/hypopigmentation
Waardenburg syndrome => telecanthus (widening of medial canthi)
Noonan syndrome clx
Bleeding diathesis (F11 deficiency), short stature, congenital heart defect (pulmonary stenosis), pectus excavatum, webbed neck, low set ears, hypertelorism, lymphedema
Infant newborn screen +for CF, what next?
Sweat chloride testing
PHACES syndrome
Posterior fossa malformation, Hemangioma (large segmental face, unilateral or bilateral), Arterial anomalies (head and necK), Cardiac anomalies (CoA, PDA, VSD, ASD), Eye abnormalities (Horner, cataract, optic atrophy), Sternal clefting
Kabuki syndrome
Clx: Arched eyebrows, long eyelashes, long palpebral fissures with lower eyelids turned out, large protruding earlobes, intellectual disability
Tuberous Sclerosis
HAMARTOMAS: Hamartomas in CNS and skin, Angiofibromas skin, Mitral regurgitation, Ash-leaf spots (hypomelanotic macules), Rhabdomyoma (cardiac), Tuberous sclerosis, autosomal dOminant, Mental retardation, Angiomyolipoma (renal), Seizures, Shagreen patches (grayish-brown thick leathery area with orange peel texture)
Charcot-Marie-Tooth disease
Aka hereditary motor sensory neuropathy => at 1st to 2nd decade, progressive distal weakness, sensory loss, depress/absent tendon reflexes, high-arched feet => muscle atrophy => upper extremities later in disease. Also skeletal and eye abnormalities.
Age for thyroid screening in Trisomy 21
Newborn screen => 6 months => 12 months => annually if normal
Trisomy 21 and leukemias (most likely at what age?)
AML if < 1 years old; ALL if > 1 years old
Most common heart defects in Trisomy 21
AV canal defects, VSD, ASD, ToF
Most common GI defects in Trisomy 21
Duodenal atresia, Hirschsprung disease
Newborn girl with microcephaly, ocular hypertelorism, prominent glabella, frontal bossing, beaked nose, hypotonia, seizures
Wolf-Hirschhorn syndrome
Newborn with profound hypotonia, SGA, feeding problems, FFT, bifrontal narrowing, thin upper lip, almond-shaped eyes, hypogonadism, bilateral cryptorchidism, small penis
Prader-Willi Syndrome (paterally derived deletion of 15q11-13)
Newborn with underdeveloped mandibular and zygomatic bones, absent lower lid eye lashes, microtia, stenosis of external ear canal, down-slanting palpebral fissures, coloboma, and conductive hearing loss
Treacher-Collins syndrome (mandibulofacial dysostosis type 1)
Short stature <3%ile, short length of proximal extremities (rhizomelic shortening), trident hands, stenosis of foramen magnum, macrocephaly, flat nasal bridge and midface
Achondroplasia
Most common cause of death in achondroplastic children <4 years old
Brain stem compression
Most common disease with infantile spasm
Tuberous sclerosis
Newborn with long eyelashes, hirsutism, low hairline, downward-turned mouth, IUGD, thin upper lip, micromelia, and syndactyly
Cornelia De Lange syndrome
Syndactyly also seen in Smith-Lemli-Opitz Syndrome and Apert Syndrome (SLO also has microcephaly with narrow bifrontal diameter, broad nasal tip with anteverted nares, hypertelorism and ptosis, cleft palate, micrognathia, and low-set ears) (Alpert syndrome also has craniosynostosis and broad thumb)
Long eyelashes also seen in Kabuki Syndrome => Arched eyebrows, long palpebral fissures with lower eyelids turned out, large protruding earlobes, intellectual disability
Infant with macrodactyly (large digits), hemihypertrophy, lipoma, hemangioma, soft-tissue hypertrophy, and accelerated growth
Proteus syndrome
vs Beckwith-Wiedemann which also has hemihypertrophy and tissue hypertrophy => also hypoglycemia, omphalocele, Wilms tumor
vs Soto syndrome which has large hands and feet instead of digits, LGA, macrocephaly, prominent forehead, hypertelorism, intellectual disability, large hands and feet
Newborn with LGA, macrocephaly, prominent forehead, hypertelorism, intellectual disability, large hands and feet
Soto syndrome
vs Proteus syndrome => macrodactyly (large digits), hemihypertrophy, lipoma, hemangioma, soft-tissue hypertrophy, and accelerated growth
Brachycephaly, frontal bossing, wormian bones, hypoplastic or absent clavicles, delayed eruption of deciduous teeth, and joint laxity
Cleidocranial dysostosis (Cleido = Clavicle)
Newborn with craniosynostosis, brachycephaly, strabismus, hypertelorism, maxillary hypoplasia, beaked nose, proptosis, syndactyly, single nail, broad thumb
Apert syndrome
Newborn with craniosynostosis, short stature, deviated nasal septum, malocclusion, malposed teeth, and without limb abnormalities
Crouzon syndrome
Newborn with craniosynostosis, broad thumb and toes
Pfeiffer syndrome (vs Apert syndrome which also has maxillary hypoplasia, syndactyly, and proptosis)
Friedreich ataxia
Path: autosomal recessive trinucleotide repeat of frataxin gene (iron binding protein) => impaired mitochondrial function => degeneration of spinal cord tracts. Clx: Muscle weakness, loss of DTRs, loss of sensation, staggering gait, nystagmus, kyphoscoliosis, pes cavus, diabetes, hypertrophic cardiomyopathy
