ULTIMATE SYNDROME DECK Flashcards
Facies - upslanting palpebral fissures, epicanthal folds, low set ears, flat nasal bridge
Sandal gap, single palmar crease
AVSD
Hypotonia
T21
Acute megakaryoblastic leukaemia
ALL/AML
T21
Deafness Vision problems Hypothyroidism Coeliac Duodenal atresia T1DM
T21
Eunochoid body habitus Gynaecomastia Small testes Low IQ ANgry/ASD/ADHD/emotionally immature
Kleinefelter XXY
Mitral valve prolapse
Kleinefelter XXY
Breast Ca, extra gonadal germ cell tumours
Kleinefelter XXY
Short stature Infertility/ovarian failure Increased upper:lower segment Defective dental development Recurrent otitis media Sensorineural deafness
Turner XO
Aortic arch malformation, bicuspid aortic valve, coarctation
Turner XO
Oedema of hands and feet at birth
Turner XO
Micro/anophthalmia Cleft lip/palate Postaxial polydactyly Scalp defects VSD/PDA/ASD Coloboma
T13 - Patau
Rockerbottom foot FIsted hands Wizened features VSD/PDA IUGR Meckel's, malrotation or omphalocele
T18 - Edward
Short Puffy eyes Long flat philtrum Dev delay Over friendly, socially disinhibited, ADHD, excessive empathy
William Syndrome
Supravalvular aortic stenosis
Peripheral pulmonary stenosis
William Syndrome
Hypercalcaemia
Hypercalcuria
Early puberty
William
Cardiac - truncus arteriosis, ToF, IAA Abnormal facies - prominent nose w large nares, small mouth, small ears Thymic hypoplasia (impaired T cells) Cleft palate Hypocalcaemia
22q11 DiGeorge
“CATCH22”
Pre and post-natal growth restriction Microcephaly Greek helmet facies Severe ID Recurrent aspiration ASD, VSD, PS
Wolf Hirshom
What is most common and second most common trisomy?
1 - T21
2 - T18
Most common translocation assoc w T21?
14;21
if 21;21 then recurrence rate is 100%
Inheritance of William?
AD, usually de novo
Failure of 3rd & 4th pharyngeal pouch to form?
22q11 - Di George
Genetic cause of Prader-WIlli?
Absence of paternal 15q
Either de novo deletion (70%) or maternal uniparental disomy (28%)
2% have mutation/deletion in imprinting centre - 50% inheritence
Neonatal hypotonia Undescended testes Voracious appetite +++ ID Obesity Hypopigmentation Small hands/feet
Prader-Willi
Premature adrenarache w delayed other secondary sex characteristics OCD, autism Cognitive impairment Epilepsy Scoliosis
Prader-Willi
Genetic cause of Angelman?
Deletion of maternal 15q
70% de novo deletion
5% paternal uniparental disomy
Microcephaly ID w absent speech Hand flapping Ataxia Laughter Loves water
Angelman
Abnormal EEG with large amplitude slow spike waves in the absence of seizures
Angelman
Genetic cause of BWS?
Paternal over expression at 11p13 resulting in overactivity of IGF2
Assoc w IVF (loss of IC2 methylation)
Sporadic (85%)
AD (15%)
Macrosomia, macroglossia, hemihypertrophy Abdominal wall defects Dysmorphic ears Hyperinsulinism, hypoglycaemia Wilms, hepatoblastoma, neuroblastoma
Beckwith Widemann
Which phenotypic factor is most strongly associated w tumour development in BWS?
Hemihypertrophy
Risk period of tumour development in BWS?
0-8 years
USS 3/12 until age 8
Genetic cause of Russell Silver?
Maternal over expression at 11p resulting in underactivity of IGF2
60% sporadic deletion, 10% maternal uniparental disomy
SGA w large head Prominent forehead, triangle face Hemihypertrophy Hypotonia Hypoglycaemia
Russel Silver
Hirsutism Unibrow, long eyelashes Ulnar ray defect Severe GOR PS, VSD, ASD
Cornelia de Lange
Inheritance of Cornelia de Lange?
Single gene mutation
NIPBL = 60%
SMC1A = 5%
Usually AD, de novo
Short stature Webbed neck PVS Dev delay Coag defects
Noonan
Inheritance of Noonan?
Single gene
PTPN11 - 50%
Interrupts Ras-MAPK
AD 2/3 de novo
Lentigines ECG conduction defects & HOCM Ocular hypertelorism Pulmonary stenosis Abnormalities of genitalia Retarded growth Deafness
LEOPARD syndrome
FTT Dev delay / ID Coarse facial features, loose skin w deep palmar/plantar creases Papillomata of face & perianal region Hypotonia, joint laxity, tight achilles
Costello
Inheritance of Costello?
Single gene
HRAS missense mutation causing defect in Ras/MAPK
Prolonged feeding abnormality -> FTT Seizures Tall forehead, low ears, sparse curly hair Hyperkeratosis Dystrophic nails HOCM, PS
Cardiofacicocutaneous syndrome
Inheritance of Cardiofacicocutaneous Syndrome?
Single gene
AD
BRAF/MAP2K/KRAS
Overgrowth (height & HC >2SDs above)
High hair line
Broad & prominent forehead
Learning disability
Sotos syndrome
Inheritance of Sotos?
Single gene
NSD1
AD >95% de novo
Tall, long limbed, thin Joint hypermobility Aortic dissection/AR/MR Chest wall deformity Lens dislocation UPWARDS Normal IQ
Marfan
Inheritance of Marfan?
Single gene
FBN1
Defective fibrillin (connective tissue)
75% have one affect parent, 25% de novo
Tall, long limbed ID Lens dislocation (DOWNWARDS) Thromboembolism Seizures
Homocystinuria
Investigation and management for homocysteinuria?
Plasma total homocysteine and methionine will be markedly elevated
B6 if responsive, methionine restricted diet, folate & B12
Inheritance of homocysteinuria?
Single gene
CBS mutation
AR
Fractures Dental abnormalities Hearing loss Blue sclera Osteoporosis Wormian bones
Osteogenesis Imperfecta
Inheritance of OI?
Single gene COL1A1 most common COL1A2 second most common Classic OI - 60% de novo Deforming/perinatally lethal OI - 100% de novo
Short limbed dwarfism Proximal limbs Midface hypoplasia Hyperextensible joints Delayed motor milestones Sleep apnoea
Achondroplasia
Inheritance of Achondroplasia?
Single gene
FGFR3 - fibroblast growth factor
AD - 80% de novo
Homozygous mutation usually lethal in newborn period
Intrahepatic biliary dysgenesis Butterfly vertebrae Pulmonary stenosis Tubulointerstital nephropathy/structural renal abnormalities Posterior embryotoxin
Alagille Syndrome
Inheritance of Alagille?
Single gene JAG1 - most common NOTCH2 - second 30-50% inherited, 50-70% de novo AD
Coloboma Heart defect choAnal atresia Retarded growth & dev Genital abnormalities Ear abnormalities "snipped off helix"
CHARGE
Inheritance of CHARGE?
Single gene
CHD7
AD usually de novo
Deafness
Ear abnormalities
Brachial fistulae/cysts under SCM
Renal agensis/hypoplasia/dysplasia
Brachio-Oto-Renal syndrome
Inheritance of Brachio-Oto-Renal syndrome?
SIngle gene
EYA1 mutation
AD
Abnormalities of 1st and 2nd brachial arches
Cone-rod dystrophy Obesity Insulin resistance Progressive sensori-neural hearing loss Dilated/restrictive cardiomyopathy Multiple organ failure
Alstrom syndrome
Rod-cone dystrophy (night blindness by 7-8, legal blindness by 16) Truncal obesity Post-axial polydactyly Cognitive impairment/learning idsability Urogenital abnormalities
Bardet-Biedel
Growth deficiency, reduced subcut fat
Erythematous, sun sensitive skin with cafe au lait spots
Microcephaly
Prominent ears and predisposition to otitis media and recurrent sinus/resp infections
Diabetes
Infertility
50% cancer risk by age of 25
Bloom syndrome
Supernumerary teeth
Bone abnormalities
Cleidocranial dysostosis
Large ears and nose, sunken eyes Short stature Neurological degeneration Cataracts, pigmented retinopathy Sun sensitivity
Cockayne syndrome
Skeletal malformation of radial/thenar/carpal bones Vertebral anomalies Sloping shoulders Secundum ASD, VSD Cardiac conduction disease
Holt Oram
Segmental/patchy overgrowth syndrome
Normal until toddler years
Pre-disposition to tumuors, DVT and PE
Proteus syndrome
Bitemorpal narrowing and ptosis with upturned nostrils 2-3 syndactyly Post-axial polydactyly Microcephaly & ID Growth retardation Cleft Congenital cataracts Anomalous pulmonary venous return High cholesterol
Smith-Lemli-Opitz
Hemifacial microsomia Conductive hearing loss Manibular abnormalities Vertebral defects ToF/VSD
Goldenhar
Hypoplasia of midface
Ear abnormalities, conductive hearing loss
Eyelid coloboma, sloping eyes, no lower eyelashes
Treacher-Collins
Micrognathia
Glossoptosis
Cleft palate
Airway obstruction & feeding difficulties
Pierre-Robin Sequence
Cause of Pierre-Robin Sequence?
Mandibular hypoplasia, prior to week 9 post-conception
Under-developed lower jaw leads to abnormal placement of tongue, cleft palate and airway obstruction
Commonest syndrome assoc w PRS?
Stickler syndrome
PRS +
Myopia/cataract/retinal detachment
Hearing loss - conductive and sensorineural
SUFE/Perthes
Stickler syndrome
Large ears Macro-orchidism post puberty Long face & prominant jaw Dev delay at 2-4years and ID (IQ 30-50) ASD/eye contact avoidant
Fragile X
Inheritance of fragile X?
X linked domiannt (females may have symptoms)
Trinucleotide repeat disorder <55 repeats normal, 55-200 “pre-mutation”, >200 full mutation
CANNOT BE DETECTED ON MICROARRAY/SEQUENCING - needs PCR or southern blot
Fragile X premutation presentation?
Shy, late onset cerebellar ataxia and intention tremor
Progressive motor, cognitive and psychiatric disturbance
Average age of onset 35-45
Huntington’s
High pitch cat like crying Round face, downslanting palpebral fissures, broad nose, low set ears Microcephaly FTT Hypotonia Psychomotor delay
Cri du Chat
Partial deletion chromosome 5
Bifid uvula Aortic dilatation Wide spaced eyes Scoliosis Joint laxity Talipes
Loeys-Ditz syndrome
Flat philtrum Thin upper lip Jittery babies Reduced brain volume Learning disability/dev delay Short stature, microcephaly ASD/VSD, conotruncal defects
Fetal Alcohol Syndrome
Vertebral anomaly Anal abnormality Cardiac - VSD/TOF Tracheo-oesophageal fistula Renal anomaly (single umbi artery) Limb abnormality
VACTERL association
Not a syndrome- unknown cause
