Syndrome Cram Flashcards
Difference between Prader-Willi and Angelman?
Both 15q11-13 - Prader-Willi only maternal contribution, Angelman only paternal contribution
PW - hypotonia, FTT, feeding difficulty then overeating & obesity and mild ID in childhood. SNRPN gene
Angelman - hypertonic, severe ID and intractable seizures. UBE3A gene
Short and obese child DDx?
PWS - hypotonia infancy, mild ID
Bardet-Biedel - renal anomalies, loss of vision, hypogenitalism
16p11.2 deletion obesity without overeating behaviour
Cohen - “wave shaped” palpebral fissures and microcephaly
Difference between BWS and Russel-Silver?
Both 11p15 methylation, IGF-2 gene affected.
BWS paternal UPD, RS maternal UPD. RS can also be caused by maternal UPD on 7
BWS - macrosomia, macroglossia, omphalocele, hemihypertrophy,
RS - IUGR, growth retardation, hemihypertrophy, neurodev delay
BWS malignancy risk?
Wilms - abdo US 3/12
Hepatoblastoma - serum AFP
Screen until age 8
Coat hanger ribs/bell shaped chest?
Paternal UPD 14q
Williams syndrome genetic cause, test of choice and clinical manifestations?
7q11 microdeletion, test w FISH for 7q
Elf like features. ID & cocktail party personality
Supravavular aortic stenosis (sometimes peripheral pulmonary stenosis), prolonged QT, SCD due to outflow tract obstruction
High calcium
Inguinal hernia, diverticula
DiGeorge/22q11/velocardiofacial syndrome genetic cause, test of choice and clinical manifestation?
Autosomal dominant 22q11 causing disruption of 3rd & 4th pharyngeal pouch. FISH for 22q
Conotruncal defect - ToF, truncus, IAA
Hypoplastic thymus - lymphopenia (1% have SCID)
Hypocalcaemia
Cleft palate
Psychosis
1q21.1 microdeletion vs duplication
Microdeletion - microcephaly ?TAR ?schizophrenia
Duplication - macrocephaly
15q11.2 microdeletion
Neurodev delay
Language delay
Psychosis
16p13.11 deletion
Short stature
Dev delay
Behaviour/psychiatric problems
Idiopathic epilepsy
Most common form of inherited intellectual disability?
Fragile X
Most common cause of primary hypogonadism?
Kleinfelter
Kleinfelter clinical presentation?
Hypospadias/cryptochordism/micropenis Learning disability/autistic traits/behaviour problems Delayed puberty, small testes Gynaecomastia INFERTILITY
Turner clinical presentation?
Short stature Congenital lymphoedema Early ovarian failure/primary amenorrhea Risk of gonadoblastoma Aortic valve disease (bicuspid), aortic dilatation/dissection Autoimmune endocrinopathy - hypothyroidism, DM Renal anomalies Otitis media/conductive hearing loss
Impact of extra sex chromosomes on phenotype?
For every extra sex chromosome IQ drop of 10 and more severe phenotype
Trisomy 18/Edward clinical presentation?
IUGR & polyhydramnios Hypertonia Prominent occiput w small mouth and micrognathia Flexed overlapping fingers Horseshoe kidney
Trisomy 13/Patau clinical presentation?
Micro/anophthalmia Cleft lip and/or palate Postaxial polydactyly Holoprosencephaly Cardiac anomalies
Trisomy 8 clinical presentation?
Always mosaic otherwise FIDU
Genesis of corpus callous & ventriculomegaly
Noonan Syndrome clinical presentation?
Dysmorphic face
Dev delay
Chest wall deformity
Pulmonary valve stenosis/hypertrophic cardiomyopathy
Cryptorchidism
Lymphatic dysplasia/easy brushing & bleeding (partial FVII def)
Genetic cause and of Noonan?
Autosomal dominant RAS-MAPK defect
Malignancy risk in Noonan?
JMML
CHARGE genetic cause and presentation?
Autosomal dominant CHD7 gene mutation Coloboma Heart defect choanal Atresia Retardation of growth/dev Genitourinary anomalies Ear anomalies
Alagille genetic cause and presentation?
Autosomal dominant JAG1/NOTCH2
Paucity of intralobar bile ducts (cholestasis, hepatitis, jaundice, cirrhosis)
Peripheral pulmonary stenosis (less common TOF)
Butterfly vertebrae
Posterior embryotoxin
Renal abnormalities
Marfan syndrome genetic cause and key clinical findings?
FBN1 autosomal dominant
Aortic root dilatation
Ectopia lentis
Differential diagnosis of patient with marfanoid features (tall, lanky, hyper mobile, high arched palate) and differentiating features?
Marfan - ectopia lentis with upwards dislocation and aortic root dilatation, normal intellect
Homocysteinuria - ectopia lentis with downward dislocation, mental retardation
Loueys-Dietz - bifid uvula, cleft palate/craniosynostosis, velvet skin
Stickler - Pierre robin sequence with myopia/glaucoma/retinal detachment
Kleinefelter - small testes, mental retardation
Osteogenesis imperfect genetic cause and clinical presentation?
Autosomal dominant mutation of collagen COL1A1/COL1A2 gene Bone breaks/"wormian" bones Short stature Scoliosis Blue sclera Hearing loss
Triplet repeat disorders?
Fragile X
Friedrich Ataxia
Myotonic Dystrophy
Fragile X genetic cause, test of choice and clinical presentation?
X-liked recessive trinucleotide repeat disorder Triplet repeat measurement of FMR1 gene Long face, high arched palate Mitral valve prolapse Large testes Mental retardation. Behavioural/autism
Friedrich ataxia genetic cause, test of choice and clinical presentation?
Autosomal recessive trinucleotide repeat disorder
GAA triplet repeat expansions in frataxin (FXN) gene
Teenage onset gait ataxia, weakness, loss of deep reflexes
Hypertrophic cardiomyopathy
Scoliosis
Diabetes
Myotonic Dystrophy genetic cause, test of choice and clinical presentation?
Autosomal dominant trinucleotide repeat disorder
CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene
Weak facies
Muscle weakness AND PAIN. Myotonia (delayed muscle relaxation)
Respiratory insufficiency
Cardiac conduction abnormalities/cardiomyopathy
Cataracts
