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
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
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
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
5
Q
Variations in Turner Syndrome
A
Y chromosome material - higher risk of gonadoblastoma in streak gonads
Ring chromosome
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
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
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
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
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
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
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
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
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
15
Q
Chotzen Syndrome
A
- AD, MC syndromic cause of CS
- Multiple suture involvement causes plagiocephaly
- Ptosis, facial asymmetry
