Syndromes Flashcards

1
Q

IPEX Syndrome

A
  • Foxp3 defect (transcription factor that controls development and function of Treg cells)
  • X-linked
  • Immune dysfunction, Polyendocrinopathy, Enteropathy
  • Autoimmune features:
  • -> Endocrinopathy: diabetes, thyroiditis
  • -> Diabetes develops by first few weeks of life
  • -> Enteropathy: diarrhoea –> FTT
  • -> Haemolytic anaemia, autoimmune neutropenia, ITP
  • Atopic features:
  • -> Eczema, food allergies, eosinophilia
  • Haem features:
  • -> Lymphadenopathy, splenomegaly
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2
Q

Wolfram Syndrome 1

A

WFS1 gene on Ch 4p - sometimes associated with mitochondrial mutations

  • Characterised by optic atrophy, SNHL, DI and IDDM
    1. Non-autoimmune, insulin dependent diabetes in first decade
  • Some are severely insulinopenic, others have high levels
    2. Diabetes insipidus and hearing loss in second decade
    3. Renal tract abnormalities develop in third decade
    4. CNS symptoms e.g. cerebellar ataxia and myoclonus develop in fourth decade
    5. Death usually occurs ~30yo (median) secondary to neurorespiratory causes
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3
Q

Smith-Lemli-Opitz Syndrome

A
  • AR, mutation in sterol 7-reductase gene located on 11q12-q13. Low plasma cholesterol with elevated 7-dehydrocholesterol –> levels not correlated with severity
  • Growth retardation, microcephaly, ptosis, anteverted nares, cleft palate (not lip), syndactyly of 2-3 toes and severe cognitive impairment
  • Causes 46XY DSD in boys with undervirilisation + absent mullerian duct derivatives. 46XX girls have normal genitalia
  • Type 1: severe disease, lethal in 1st yr of life, assoc. w/ pyloric stenosis
  • Type 2: assoc. w/ cleft palate and Hirschprung’s disease
  • Maternal apolipoprotein E values seem to correlate with dz severity
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4
Q

DiGeorge Syndrome

A
  • Heterozygous deletion of Chr 22q11.2
  • Abnormal development of 3rd and 4th branchial pouches
  • CF:
  • -> Conotruncal cardiac defects 80%
  • -> Hypocalcaemia 60% - parathyroid aplasia/hypoplasia, may improve later in life due to compensation of residual tissue
  • -> Thymic aplasia/hypoplasia –> immune deficiency
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5
Q

Variations in Turner Syndrome

A

Y chromosome material - higher risk of gonadoblastoma in streak gonads
Ring chromosome

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6
Q

Turner Syndrome

A

45X0

  • Haploinsufficiency of SHOX gene: short stature
  • Cardiac defects: aortic stenosis, CoA
  • Autoimmune dz: autoimmune thyroid disease, T1DM, coeliac dz
  • Renal abnormalities: horseshoe kidney
  • Audiology: short, narrow ear canals, SNHL
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7
Q

Trisomy 13 (Patau Syndrome)

A
  • Genetics: nondisjunction (advanced maternal age), rarely translocation
  • Key features: midline defects - holoprosencephaly, cleft lip/palate, cardiac defects, scalp defect (hair/skin), normal growth
  • Genetic test: karyotype/FISH/microarray
  • Prognosis: median survival 10 days, 80% die by 3mths, 92% by 1yr, profound intellectual disability in long-term survivors, often lethal
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8
Q

Prader-Willi Syndrome

A
  • Genetics: imprinting defect at 15q - loss of paternally active genes (pat deletion, pat imprinting defect, mat UPD)
  • CF: neonatal hypotonia (poor feeding/suck), undescended testes and micropenis, hyperphagia after infancy –> obesity, hypopigmentation, small hands and feet, endocrinopathies due to abN hypothalamic signals
  • Dysmorphism: almond-shaped eyes, micrognathia
  • Prognosis: risk of obesity, GH widely used, ID mild, behavioural issues
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9
Q

CHARGE Syndrome

A

Coloboma of eye or microphthalmia, cranial nerve abN
Heart defects
Choanal atresia/stenosis
Growth retardation +/- developmental delay with learning difficulties
Genitourinary defects e.g. hypogonadism, UDT
Hearing loss with abnormally-shaped ears - concave, malformed pinna
Others: tracheo-oesophageal fistula, orofacial cleft
Mutation in CDH7 gene - AD or de novo

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10
Q

Cardiovascular abnormalities in Turner Syndrome

A

39% Bicuspid aortic valve
31% Elongation of aortic arch
15% Partial anomalous pulmonary venous return
15% COA
CVS abnormalities and risk for aortic dissection strongly associated with history of foetal lymphoedema

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11
Q

Klinefelter Syndrome

A
  • 47XXY, mosaics: 46XY/47XXY, 46XY/48XXXY, 45X/46XY/47XXY
  • Impairment of linguistic competence, psychiatric problems occur early –> attention deficit (w/o impulsivity), difficulties in social interactions due to poor insight and poor judgement
  • Severe aneuploidy –> severe ID and dysmorphism
  • Hypogonadism: small testes, spermatogenic arrest and Sertoli cell predominance (major)
  • -> Pubertal onset normal, then stall with decrease in testicular size due to seminiferous tubule dysgenesis. Small penis due to low testosterone, pubertal delay and gynaecomastia.
  • -> Azoospermia and infertility
  • Normal adrenarche
  • Risk of breast cancer (same as women)
  • Tall stature (>2SD above MPH) with US:LS disproportion (<0.9) - delayed epiphyseal closure due to hypogonadism, long limbs
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12
Q

Crouzon Syndrome

A
  • AD, FGFR2 mutation
  • Craniosynostosis - most commonly brachycephaly due to premature coronal synostosis
  • Orbital underdevelopment and maxillary hypoplasia –> proptosis, hypertelorism –> strabismus
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13
Q

Apert Syndrome

A
  • Sporadic > AD, FGFR2 mutation
  • Craniosynostosis classically involving multiple sutures –> higher risk of raised ICP + neurological Cx
  • Can effect coronal, sagittal, lambdoidal and squamosal sutures
  • Syndactyly of 2-4th digits common
  • Less proptosis c.f. Crouzon
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14
Q

Carpenter Syndrome

A
  • AR
  • Multiple sutures fused causing kleeblattschädel skull deformity (clover-leaf)
  • Soft tissue finger and toe syndactyly
  • Intellectual impairment
  • Assoc. with heart defects, corneal opacities and genu valgus
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15
Q

Chotzen Syndrome

A
  • AD, MC syndromic cause of CS
  • Multiple suture involvement causes plagiocephaly
  • Ptosis, facial asymmetry
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16
Q

Pfeiffer Syndrome

A
  • Sporadic > AD
  • Turricephaly (cone head) due to coronal, sphenofrontal and frontoethmoidal suture fusion
  • Hypertelorism
  • Short, broad thumbs and great toe, partial syndactyly
17
Q

General complications from craniosynostosis syndromes

A
  • Hydrocephalus, papilloedema, raised ICP –> craniectomy Sx necessary
  • Optic nerve atrophy due to optic foramina abN
  • Respiratory abN due to deviated nasal septum, choanal atresia
  • Disorders of speech and deafness
18
Q

Alagille Syndrome

A
  • AD, JAG1 mutation on chr20p or NOTCH1
    –> Protein ligand involved in intracellular signalling
  • Facies: frontal bossing, moderate hypertelorism, deep set eyes, broad nasal bridge, long nose with bulbous tip, pointy chin
  • Neonatal cholestasis: initial bile duct prolif –> paucity +/- paucity of extrahepatic ducts and GB
  • R) heart lesions (peripheral pulmonary artery stenosis, TOF)
  • Posterior embryotoxon, abN radii, vertebral abN (butterfly vertebrae, hemivert), def in fat sol vitamins
    Minor: short stature, high-pitched voice, renal anomalies (horseshoe, cystic, hypoplastic), hypercholesterolemia, intracranial vascular malformations (prone to haemorrhage)
19
Q

BASM (Biliary atresia Splenic Malformation) Syndrome

A
  • Biliary atresia
  • Polysplenia (functionally asplenic)
  • Intestinal malrotation
  • Midline liver
  • Abdominal situs inversus
  • Portal vein abnormalities and interrupted IVC
    +/- cardiac anomalies
20
Q

Gorlin Syndrome

A
  • PTCH gene mutation
  • Predisposes to basal cell carcinoma with first lesion appearing in mid-adolescence
  • May develop thousands of skin cancers –> indolent, but disfiguring
  • Other manifestations: medulloblastoma 5-10%, recurrent jaw cysts, calcification of falx cerebri, palmoplantar pits in older child
  • -> RTX in medullo –> accelerated BCC development in irradiated fields
  • Dysmorphism: macrocephaly, prominent forehead, hypertelorism
  • Sun protection mandatory, XR should be avoided
21
Q

Fanconi anaemia associations

A

Biallelic mutations in FANCD1/BRCA2 and FANCJ/PALB2 can also cause VACTERL associations

22
Q

Fanconi anaemia

A
  • PC macrocytic anaemia <10yo –> pancytopenia develops in 50% within 10yrs of anaemia
  • Other Sx: Cafe-au-lait spots, thumb and/or radial abN, short stature, abnormal male gonads, microcephaly, eye abN, structural renal defects, LBW, developmental delay, abN hearing
  • 10-30% have cancer predisposition e.g. AML
23
Q

DDx for cafe-au-lait

A
  • NF1 and NF2
  • McCune Albright Syndrome
  • Fanconi Anaemia
  • LEOPARD syndrome (lentigines, ECG conduction defects, ocular hypertelorism, pulmonary stenosis, abN of genitalia, retardation of growth, SNHL (deaf)
  • Bloom Syndrome
  • Russell-Silver Syndrome
  • Watson Syndrome
24
Q

DDx for cafe-au-lait

A
  • NF1 and NF2
  • McCune Albright Syndrome
  • Fanconi Anaemia
  • LEOPARD syndrome (lentigines, ECG conduction defects, ocular hypertelorism, pulmonary stenosis, abN of genitalia, retardation of growth, SNHL (deaf)
  • Bloom Syndrome
  • Russell-Silver Syndrome
  • Watson Syndrome
25
Q

Neonatal features of Williams Syndrome

A
  • Hypercalcemia
  • Elfin facies
  • Hypertension
  • Supravalvular aortic stenosis
26
Q

Differential diagnoses for Marfan Syndrome

A
  • Homocystinuria
  • Loeys-Dietz Syndrome
  • MEN2B Syndrome
  • Ehlers-Danlos Syndrome
  • Fragile X Syndrome
  • Stickler Syndrome
27
Q

Neonatal presentation of Prader-Willi Syndrome

A
  • Delivery: breech, reduced FM, premature
  • Dysmorphism: almond-shaped eyes, dolichocephaly, small hands and feet, narrow bifrontal diameter, downturned mouth
  • Neonatal hypotonia (axial), lethargy, decreased movements, weak cry, poor reflexes including suck, FTT
  • Hypogonadism in M: micropenis or hypoplastic scrotum, poorly rugated
  • Hypogonadism in F: small clitoris and labia from birth