Syndromes Flashcards
(43 cards)
Trisomy 18
“Edward’s syndrome”
Classic features: Choroid plexus cysts - hallmark finding Radial ray anomalies Clenched hands with crossed fingers Rocker bottom feet 2 vessel cord Oesophageal atresia Strawberry skull Cardiac abn
Imaging Increased nuchal translucency Cardiac (95%) ASD, VSD, PDA, dextrocardia CNS Choroid plexus cysts CC agenesis Dandy-Walker continuum NTD Cystic hygroma Skeletal Clenched hands with overlapping index/middle finger - crossed fingers Absent thumb Radial ray anomalies - chr of 18 Rocker bottom feet - typical Facial abn Micrognathia Cleft lip/palate Dolichocephaly - due to frontal lobe hypoplasia "strawberry skull" Hypertelorism Low set ears Strawberry sign - inward bowing frontal bones (tip of strawberry anteriorly), brachycephaly, flattened occiput Single umbilical artery Cord cysts CDH Oesophageal atresia Omphalocele Renal Horseshoe Hydronephrosis
Trisomy 13
“Patau syndrome”
Classic features Holoprosencephaly - hallmark finding Midline facial abn - cleft lip/palate Omphalocele Polydactyly CHD Horseshoe kidney and cystic renal dysplasia (enlarged echogenic kidneys)
Most only live a few days CHD Hypoplastic left heart VSD CNS Holoprosencephaly - alobar Fetal hydrocephalus CC agenesis Microcephaly Encephalocele Early IUGR Abn facies - 90% Cleft lip/palate Micrognathia Proboscis Cyclopia Hypotelorism Skeletal Polydactyly 70% - post-axial (ulnar) Rocker bottom feet Clenched hands with overlapping digits Abdo wall Bladder exstrophy Omphalocele Cystic renal dysplasia (see enlarged echogenic kidneys) - (?such as MCDK, ARPKD, obstructive cystic renal dysplasia) Horseshoe kidney Single umbilical artery DDx Meckel-Gruber - cystic renal dysplasia, polydactyly (pseudotrisomy 13)
Trisomy 21
“Down syndrome”
Antenatal
Classic features: Duodenal and oesophageal fistula (both combined) Atrioventricular septal defect Absent NB Increased nuchal thickness
Antenatal Imaging
Nuchal translucency >3mm at 11-14 weeks. Less specific for T21
Nuchal fold thickness >6mm at 15-21 weeks - most sensitive and specific sign for T21
Cardiac - TR, ASD, VSD, AVSD, TOF, endocardial cushion defect 40% Abdo Duodenal atresia Oesophageal atresia Omphalocele (more common with 18) Soft markers: Short humerus/femur Aberrant RSCA Mild pyelectasis Echogenic bowel No nasal bone ossification Nuchal fold thickness Echogenic intracardiac focus Ventriculomegaly Cystic hygroma - but more common in Turners Sandal gap toes Hypoplasia of middle phalanx of little finger - causes clinodactyly (radial angulation/curve of finger) - 60% Downs have **MCQ
T21 radiographic findings and complications
Persistent metopic suture - after age 10 (the one across the frontal bones)MCQ
Decreased acetabular angles - flattened acetabular roofMCQ
But also at risk of DDH MCQ - due to laxity of ligaments/hypotonia/capsular insufficiency rather than increased acetabular angle
Don’t typically exhibit hip dysplasia before walking age
Flared iliac wingsMCQ - rotated towards coronal plane “mickey mouse ears”
Increased iliac angle - divergent iliac wings on axial CT
Increased risk SUFEMCQ
(b/c often overweight? Or due to mechanics of abn pelvis)
Clinodactyly - bent finger, radial angulation at DIP
Short little fingerMCQ
Sandal gap toes
Multiple manubrial ossification centresMCQ
X2 (usually 1)
Atlantoaxial subluxationMCQ
11 sets of ribsMCQ
Underdeveloped paranasal sinuses
Cerebellar hypoplasiaMCQ
Other
Early onset neurodegenerative disorder in almost all pt > 40yr
Alzheimer type dementiaMCQ
Leukaemia - AML and ALL - 10-20x incr risk of acute leukaemiaMCQ
Abn immune response - predisposed to severe infection
Pathology
Most common cause is meiotic nondisjunction
Extra chrm is maternal origin in 95%
Increasing risk of nondisjunction with increasing maternal age
1% mosaic - mixture of 46 and 47-chrm cells
Milder phenotype (depends on proportion abn cells)
Due to mitotic nondisjunction
Turner Syndrome
45X0
“monosomy X”
Infertility
Caused by non-disjunction sex chrm. Can be mosaic (can look normal and present with primary amenorrhoea)
Primary hypogonadism in phenotypic female
Classic Features
Cystic hygroma
Streak like ovaries (in paed not antenatal)
Coarctation
Most common sex chrm abn in females 1:2000-5000 births NO association with maternal age Streak like ovaries - streak of fibrous tissues instead of normal ovaries (no or few follicles) Bicuspid aortic valve Horseshoe kidney**MCQ Omphalocele Lymphatic malformation - cystic hygroma (around 60% cystic hygromas are associated with aneuploidy, most commonly Turner's Aortic coarctation Short 4th MC**MCQ Madelung Short stature Webbed neck, low posterior hairline Increased valgus angle
Other Later Abn
I.e. not antenally seen
C-spine abn - hypoplasia odontoid and C1MCQ
Thyromegaly - hypothyroid, positive autoab common
Get Hashimoto-like thyroiditisMCQ
Delayed fusion of epiphyses > 20 yrMCQ
Normal skeletal maturation up until then
Possible increased risk some malignanciesMCQ
Positive carpal sign - narrowed scapholunate angle
Madelung deformity - decreased carpal angle
Short 4th MC
Primary amenorrhoea
Abn secondary sex chr - minimal breast/pubic hair
Triploidy (non-molar)
Non-molar triploid pregnancy
Is triploidy with the extra haploid chrm maternal - don’t form placenta with molar change
Can’t dx on NIPT - needs invasive testing
Entire extra chrm set
69 XXY, XXX, or XYY
Either extra set of paternal (more common - diandric triploidy) or maternal chrm
(unlike complete mole which is only paternal DNA i.e. can’t form fetal parts)
Fatal - often 1st trimester miscarriage
Rarely might survive briefly after birth
Imaging
IUGR - severe and early
Macrocephaly
Fetal hydrocephalus
Oligohydramnios
Placental abn - placentomegaly or very small
Syndactyly - fusion of fingers (bony or ST)
DiGeorge Syndrome
“22q11.2 deletion syndrome”
“velocardiofacial syndrome”
Needs invasive testing to dx (not NIPT)
Classic features:
CATCH 22
CHD - esp conotruncal
Abn facies - low set ears, hypertelorism (widely spaced eyes)
Thymic hypoplasia - don’t develop 3rd and 4th pharyngeal pouch properly. Get lymphopenia as no thymus to mature T cells
Cleft palate/cellular immune deficiency
Hypoparathyroidism/hypocalcaemia - don’t have parathyroids
22 - deletion located on chrm 22
Imaging
Cleft lip +/- palate
CHD - especially conotruncal abn
e.g. TGA, truncus arteriosus, TOF
Chr facies - long face, facial asymmetry, prominent nose, hypertelorism, low set ears, abn philtrum (conflicting whether long or short)
Hypernasal speech
Learning disabilities
Decreased immunity - T cells mature in thymus which is hypoplastic
Parathyroid and thymus abn (malfm 3rd/4th pharyngeal pouches)
Hypoparathyroidism
Hypocalcaemia
Klinefelter Syndrome
Sex chrm abn causing male hypogonadism
47XXY most common (80%)**MCQ
Can be mosaic 46XY/47XXY or 47XXY/48XXXY
Due to nondisjunction of sex chrm during meiosis
Extra X is maternal or paternal in origin
Other less frequent types
1 in 500 male births
Presentation - girly men
Postpubertal males with small testes (3-4ml on USS), gynaecomastia, subfertility
Can be clinically overlooked
Increased risk GCT - esp mediastinum (not testes)
Increased risk male breast ca (x20)
Increased risk SLE and other AI diseases
Features
Normal testes before puberty but then don’t grow or make sperm
Gynaecomastia post puberty
Clinodactyly
Tall
Incr FSH
Androgen deficiency
Sparse facial/axillary hair
Infertile unless mosaic with significant 46XY porportion (impaired spermatogenesis)
Mental retardation (can be mild)
VHL
AD inheritance
Mutations in VHL tumour suppressor gene on chrm 3 **MCQ
VHL gene 3p25
Tumours have lost VHL function - express high levels of HIF, drives VEGF/various growth factors/EPO expression
20% arise de novo
>40 different tumours (benign/malignant)
Rare: 1 in 30-40,000
Pancreatic SCN - pancreatic serous cystadenoma Islet cell tumours - pancreatic NET Simple cysts (NOT pancreatic adenocarcinoma - or maybe very rarely)**MCQ
Other abdo:
Adrenal
Phaeochromocytoma **MCQ
Extra-adrenal phaeochromocytoma/paraganglioma
Renal
RCC - clear cell (bilateral, earlier age) MCQ
Cysts
Renal cysts in paed (otherwise uncommon)
AML
Bilateral epididymal head cysts
Liver - simple cystsMCQ
CNS/H&N
Haemangioblastoma - brain and spine (cord and nerve roots) **MCQ
Endolymphatic sac tumour - vestibular aqueduct
Choroid plexus papilloma
Retinal hemangioblastoma **MCQ
Causes retinal haemorrhage or detachment **MCQ
RCC is the leading cause of death
Classic is co-existing multisystem simple cysts and malignant tumours
CNS haemangioblastoma - 2nd most common cause of morbidity/mortality
Other
Paraneoplastic polycythaemia due to EPO expression by tumours
VHL HIPPEL
• H: hemangioblastoma
• I: increased risk of renal cell cancer
• P: pheochromocytoma
• P: pancreatic lesions (cyst, cystadenoma, cystadenocarcinoma)
• E: eye dysfunction (retinal hemangioblastoma), endolymphatic sac tumors
L: liver, renal and pancreatic cysts
TS
Cause
-Faulty TSC1 (encodes hamartin) or TSC2 (encodes tuberin) gene.
mTOR (kinase regulating cell metab) activity increased when either of these are lacking = cell growth
-AD but most are sporadic
CNS
- Tubers
- Subependymal nodules
- SEGA
- Aneurysms
- Radial migration lines
Abdominal
- Renal AML
- Renal cysts in kids (+liver/panc cysts)
- Increased risk RCC (clear cell) and oncocytoma
Thoracic
- Cardiac rhabdomyoma
- LAM
Other
Other organ hamartomas - retinal, hepatic
-MSK - bone cysts, inner calvarial hyperostosis, sclerotic bone lesions, scoliosis
MEN 1
Germline mutations in MEN1 tumour suppressor gene - encodes protein called Menin
Primary HPT most common manifestation (90%) - all get by 40-50yr **MCQ
Hyperplasia and adenoma
Most common presenting abn
Pancreatic NET - leading cause of death
Aggressive, present with mets
Often functional e.g. Gastrinoma most common = Zollinger Ellison
Pituitary adenoma - prolactin secreting microadenoma most common
Less common somatoropin (GH) = acromegaly
PPP (?or PaPiPa) (or 3Ps)
Pancreatic NET - gastrinoma
Pituitary adenoma
Parathyroid adenoma (think FRCR case)
MEN2A
Thyroid - medullary carcinoma before 20yr
Variant - familial medullary thyroid cancer (don’t have the other tumours) - older age onset, more indolent cause
Adrenal medulla - pheochromocytoma in 50%
Only 10% malignant (same as sporadic phaeo)
Parathyroid - hyperplasia in 10-20%
Present with primary HPT
MPP (or MPhP?) (or 1 M, 2 Ps)
Medullary thyroid
Pheochromocytoma (and paraganglioma generally)
Parathyroid adenoma
MEN 2B
Different RET mutation than MEN2A
Medullary thyroid ca - multifocal and more aggressive than MEN2A
Phaeochromocytoma
Extraendocrine manifestations:
Ganglioneuroma of mucosal sites - lips, GIT, tongue (i.e. not NET)
Referred to as “mucosal neuromas” in mcq questions
Marfanoid habitus - long bones similar to Marfans
NO primary HPT
MPN (or MPhN?) (or 2 Ms, 1 P)
Medullary thyroid
Pheochromocytoma (and paraganglioma generally)
Neuromas
Carney Complex
Atrial myxoma Skin pigmentation (blue naevi)
Plus other features:
Pituitary adenoma
Psammomatous melanotic schwannoma
Testicular tumour - esp sertoli cell
NOT Carney triad (gastric GIST, pulmonary chondroma, extra-adrenal phaeochromocytoma)
(“Carney Complex has Cardiac stuff - myxoma”)
VACTERL association
Non-random association of anomalies involving many organ systems EXCEPT the brain
Heart and kidneys most important
Need x3 to call
Vertebral anomalies - hemivertebrae, congenital scoliosis, caudal regression, spina bifida
Anorectal malformation - anal atresia
Cardiac anomalies
TOF
Renal anomalies, radial ray abn (spectrum abn e.g. hypoplasia/absence radius/radial carpal bones/thumb)
Limb anomalies - polydactyly, oligodactyly
Beckwith-Wiedemann Syndrome BWS
Congenital overgrowth syndrome - increased risk childhood cancers Genomic imprinting abn Mostly sporadic. 10% AD inheritance Omphalocele Macroglossia Hemihypertrophy Visceromegaly - big organs, big spleen
Increased risk of hepatic and renal malignancies - screening USS abdo
- Wilms (most common tumour in BWS), hepatoblastoma, adrenal cortical carcinoma, pancreatic tumours - Neuroblastoma - Risk is for increased embryonal tumours
Perinatal hypoglycaemia
Pentalogy of Cantrell
From Al, everything here goes “blerrrrghgh”
Rare ++
Ectopia cordis - extrathoracic heart (remember Vim teaching case with ecoptia cordis)
Omphalocele
Diaphragmatic defect
Sternal disruption/Pericardial defect
CVS anomalies - VSD, ASD, tetralogy of fallot, LV diverticulum
Ddx
Amniotic band – can cause lots of
Meckel-Gruber Syndrome
AR inheritance
Multi-organ syndrome
Sometimes called “pseudotrisomy 13” due to overlapping features
Need renal dysplasia plus one of the other triad features
Triad of:
1. Encephalocele - occipital or holoprosencephaly
2. Cystic renal dysplasia causing multiple tiny renal cysts - look like ARPKD (?but not same) ?MCDK
3. Polydactyly - post axial (ulnar)
Other - hepatic abn/fibrosis
Raised maternal AFP
Holt-Oram Syndrome
“hand heart syndrome”
AD inheritance
Often mutation in TBX5 gene
Many other mutations
Classic
Cardiac septal defects and radial ray abn
Imaging
CHD
ASD - most common
VSD
Aortic coarctation
Radial ray anomalies - radial aplasia/hypoplasia/fusion, thumb abn e.g. aplasia
Can be asymmetrical
Phocomelia - shortening of deficiency in proximal/mid limbs e.g. thalomide
DDx
VACTERL - also radial ray abn and cardiac but need x3 to call
TAR syndrome - thrombocytopenia absent radius syndrome. Extremely rare.
Have bilateral absent radius but normal thumbs
Noonan Syndrome
Non-aneuploidic Genetically and phenotypically heterogeneous RASopathy - developmental disorders caused by germline mutation in genes coding for Ras/MAPK pathway Amplifies Ras/MAPK pathway Normal number of chrm = NORMAL karyotype Sporadic and AD inheritance Various geners - PTPN11 most common M and F affected Similar features to Turners Features Craniofacial abn Cardiac - Pulmonary stenosis (most common), hypertrophic cardiomyopathy, PDA Vascular abn - cystic hygroma, lymphoedema Short Hypotonic Dilated renal pelvises Nuchal oedema in 1st trimester
Fetal Hydantoin Syndrome
Women taking phenytoin for epilepsy during pregnancy
CNS - microcephaly
IUGR
Cardiac abn
Facial abn - cleft lip, low nasal bridge
Gu abn
Hand/phalangeal abn - hypoplasia distal phalanges fingers/toes
Fragile X Syndrome
Key MCQ facts Short boy Big balls Retarded Hyperextensible joints Long mandible Trinucleotide repeat on X chrm
Pathology
Mutation in FMR1 gene
Trinucleotide repeat mutation - more triplet repeats = worse phenotypeMCQ
Carrier males are normal
20% males with the mutation are clinically and cytogenetically normalMCQ
Can transmit via normal daughters to their grandsons
Affected females
30-50% carrier females are mentally retarded
M>F
2nd most common genetic cause of mental retardation after T21
Features
Short stature MCQ
Cognitive
Cognitive disability - more severe in MMCQ
MSK - hyperextensible jointsMCQ
CV - aortic root dilatation, MV prolapse
Facial dysmorphism - long face with large mandible (long mandibleMCQ), large everted ears
Macroorchidism - large testicles**MCQ
Only distinctive feature seen in 90% post pubertal males (other features variable++)
PHACE Syndrome
“cutaneous haemangioma-vascular complex syndrome”
Posterior fossa malformation e.g. DW
Haemangioma e.g. subglottic haemangioma, infantile haemangiomas of face and neck
Arterial anomalies - stenosis, aneurysm, agenesis
Coarctation and cardiac abn
Eye abn - coloboma, optic nerve hypoplasia
See subglottic haemangioma on e.g. ST neck x-ray – look for posterior fossa abn of PHACE
On x-ray looks like asymmetric narrowing of subglottic airway (as opposed to symmetric narrowing of croup)
