Paediatric Syndromes (Self Notes) Flashcards
Down syndrome (From SpC OG)
- Incidence: 1:600-800 (may go down due to screening + abortion)
- CHD in 40%, 70% AVSD
- Life expectancy without CHD: 60
- Death caused by infections, CHD and malignancy
- IQ 25-50, IQ for older patients 25
- Premature dementia in 40-100%
- Short stature
- Hypothyroidism
- 15-20 fold increase in the incidence of leukemia (Myeloid type 7)
- Male infertility (Female infertility not a problem, but will have 50% pass down trisomy)
Genetics (SpC Paed PP):
- Aneuploidy: Trisomy 21 (94%, related to advanced maternal age)
- Robertsonian translocation (3-4%, unrelated to maternal age)
- Mosaicism Trisomy 21 (2-3%)
Clinical features:
- Midface hypoplasia: Upslanting eyes
- Clinodactyly + Hypoplasia of middle phalanx (wedge shape: medial side affected more)
- Phenotype may change over life
Vinson Cheng:
10 Facial features:
1. Protruding tongue
2. Brachycephaly (Flat occiput)
3. Microcephaly
4. Brushfield’s spot
5. Hypertelorism
6. Epicanthal fold
7. Upslanding eye
8. Hypoplasic teeth
9. Small ears
10. Hair loss
11. Flat nasal bridge
12. Len opacity
10 Hand and Feet sign:
1. Short metacarpal bone
2. Short phalanges
3. Clindodactyly of 5th finger
4. Simian crease (single palmar crease)
5. Sandal gap
6. Ulnar loop dermal ridge pattern on all digits
7. Palmar triradius
8. Plantar crease between 1st and 2nd toes
9. Cutis marmorata
10. Hyperkeratotic skin with time
Patau syndrome (Trisomy 13) (From SpC OG)
- Incidence: 1:8000 liveborn
- Due to non-disjunction: 80% (Robertsonian chromosomal translocation 20% —> Need to do Karyotype to find out)
- Congenital heart disease: 80%
- Most common CHD: ASD, TOF, TGA
- Prenatal death (Spontaneous / Stillbirth): 50%
- Only 5% of the live born make it to 1 year
Clinical features:
- Midline cleft
- Polydactyly
- Cyclopia
- Holoprosencephaly
- Cepocephaly (monkey face)
Edwards syndrome (Trisomy 18) (From SpC OG)
- Incidence: 1:3000 liveborn
- 80% females
- 90% due to non-disjunction
- Cardiac abnormalities: 100%
- Most common CHD: VSD, Myxomatous changes of the valves
- Prenatal death in 75%
- Only 5% of the liveborn reach 1 year of life
Clinical features:
- Mild facial features
- IUGR
- Clenched fist
- Rocker bottom feet
Turner syndrome (45, X) (From SpC OG)
**45X:
- Phenotypic females lost an entire / a portion of X chromosome that includes the tip of its short arm (SpC Revision)
—> include **tip of short arm
- Haploinsufficiency of genes on X chromosome
Epidemiology:
- affects approximately 1/2500 live female births, 2% of all conceptions (i.e. 95% are miscarried)
- only 1% of embryo survive to term
—> responsible for 7-10% of all spontaneous abortions
Genotype vs Phenotype:
- Various type of karotypic abnormalities (~50% classical 45X)
—> others karyotypes can also lead to TS (e.g. 46 Xi)
Clinical features:
2 common features (>90%):
1. **Short stature
2. **Premature ovarian failure
Other features:
1. **Micrognathia
2. **↑ Carrying angle (cubitus valgus)
3. ***Concave hypoplastic nails
4. Cystic hygroma
5. Neck edema —> Webbed neck
6. Cardiac defects are found in 75%, 35% liveborn have cardiac abnormalities
- Bicuspid aortic valve
- Coarctation of the aorta
- Aortic stenosis
- Hypertension
- Dilatation of aortic root
7. Renal anomalies
8. Autoimmune hypothyroidism
9. IBD
10. Hearing loss
11. DM
12. Osteoporosis
Variability of phenotypes in TS:
- Early surveys emphasised physical traits (typical clinical features: webbed neck, low-set / malrotated ears, ptosis, skeletal abnormalities)
- BUT only 50% truly dysmorphic
Management:
1. GH treatment (for short stature)
2. Monitor pubertal development +/- Estrogen replacement (for gonadal insufficiency)
3. Refer cardiac (for CVS problems) (need continuous monitoring ∵ conditions can occur later in life)
4. Refer USG (for renal abnormalities)
5. Screening TFT (for autoimmune hypothyroidism)
6. Refer ENT (for hearing loss)
From JC119:
Phenotype highly variable
1. Short stature
2. **Low posterior hairline
3. **Low set ears
4. Narrow, high arched palate
5. **Webbed neck
6. **Broad chest with widely-spaced nipple
7. **Cubitus valgus (↑ carrying angle)
8. **Left-sided cardiac lesions (e.g. **Coarctation of aorta, **Bicuspid aortic valve)
9. ***Horseshoe kidney
10. Streak ovaries, amenorrhoea, infertility
11. Hypothyroidism
12. Concave hypoplastic nail (SpC Revision)
(Normal intelligence)
SpC Revision:
- Sporadic disorder with complete / partial absence of 2nd X chromosome
- Incidence 1 in 2000-2500 live female births
- Should be considered in short girls, even in the presence of pubertal signs (∵ can have Mosaic turner)
- Marked serum gonadotropins from as early as 8-9 years (∵ lack of negative feedback)
- Pure XX and XY gonadal dysgenesis both present with delayed puberty, ↑ Gonadotropins + ↓ Sex steroids
- The XY gonadal dysgenesis group reared as girls have high risk of gonadal tumours, thus need surgery for removal of gonads
Noonan syndrome (From JC119)
- Autosomal Dominant (Vinson Cheng)
- Genetic mutation (e.g. ***PTPN11 mutation (SpC Revision))
- a ***RASopathies (along with Costello syndrome, CFC (Cardiofaciocutaneous syndrome)
- Atypical facial appearance
- **(Orbital) Hypertelorism
- **Downward slanting eyes
- ***Low set, abnormally shaped / posteriorly rotated ears - Short stature
- ***Broad / Webbed neck
- Heart defects
- **Hypertrophic obstructive cardiomyopathy
- ASD, VSD
- **PS - Vision problems
- Hearing loss
- Abnormal bleeding / bruising
- ***Pectus excavatum / carinatum
- Mild developmental delay / Intellectual disability
Russell-Silver syndrome (From JC119)
Cause:
- Largely unknown
- mat dup 11p15.5 (also implicated in Beckwith-Wiedemann syndrome)
- matUPD7
- Born SGA / Low birthweight (< -2 SD) (IUGR-related (SpC Revision))
- Short stature (< -2 SD)
- ***Relative macrocephaly (Normal head circumference which may appear large ∵ small body size)
- ***Triangular face
- ***Broad forehead
- ***Pointed chin
- ***Clinodactyly of 5th finger (尾指歪左)
- ***Limb / body / facial asymmetry / hemihypertrophy
- Hypospadias
- ***Feeding difficulty during infancy
- Hypoglycaemia (need GH supplementation for low glucose + poor growth)
- Normal head circumference (SpC Revision)
- Developmental delay
- Urogenital features (e.g. Hypospadias, Urethral valves, Horseshoe kidneys, Cryptochidism)
Beckwith-Wiedemann syndrome (BWS) (From JC122)
- ***Imprinting gene disorder
- Imprinting gene (60 in body):
—> important in development / growth
—> important whether come from father / mother
—> usually monoallelic expression (only 1 copy expressed, depends on origin e.g. father / mother)
Overgrowth syndrome:
- Abnormal regulation of imprinted region ***11p15
—> IGF2, KCNQ1 expressed in paternal allele —> promote growth
—> H19, CDKN1C expressed in maternal allele —> suppress growth
- if balance offset (e.g. ↑ methylation of H19 / ↓ methylation of KCNQ1 (i.e extra expression) —> Beckwith-Wiedemann syndrome (BWS)
(- Opposite: Russell-Silver syndrome (self notes))
- Risk of embryonal cancer (e.g. **Hepatoblastoma, **Wilms’ tumour (Nephroblastoma))
BWS subgroup:
1. Paternal UPD
2. ***Hypomethylation on DMR2
3. Hypermethylation on DMR1
Management:
1. Monitor for **hypoglycaemia in neonatal period (∵ cells more demanding)
2. Cancer surveillance for **embryonal tumour (Hepatoblastoma, Nephroblastoma)
3. **Abdominal USG every 3-6 months until 8 yo
4. **AFP concentration measurement in first 4 years of life for hepatoblastoma early detection
Prader-Willi syndrome (From JC119)
- Short stature
- ***Long + Narrow head at birth
- ***Narrow face
- ***Distinct almond shaped eyes
- Small mouth + corners curved downward
- Thin upper lip
- Small upturned nose
- ***Small hands + feet
- ***Hypogonadism leading to genital hypoplasia (Felix Lai)
—> Cryptorchidism
—> Scrotal hypoplasia
—> Labia minor / Clitoral hypoplasia - ***Obese (not a must) (Vinson Cheng)
- ***Mental retardation
- **Genomic Imprinting: deletion of the **paternal copies of SNRPN and Necdin genes
- Dolichocephaly (SpC Revision)
- ***Hypotonia + Poor feeding —> Failure to thrive
- Treatment: ***GH injection (Growth promoting effect + Lipolytic effect)
Mucopolysaccharidosis (MPS) (From JC119)
MPS subtypes share common characteristics + is a progressive multisystemic disorder
- MPS type 6: Maroteaux-Lamy syndrome
- MPS type 4a: ***Morquio syndrome
- MPS type 1: Hurler syndrome
Facial features:
1. Broad nose
2. Flat nasal bridge
3. **Prominent eyes
4. Enlarged tongue + lips
5. **Prominent forehead
6. ***Macrocephaly
7. Coarse hair
Extra-skeletal symptoms:
1. **Chronic rhinitis / otitis media
2. Obstructive airway disease
3. Skin thickening
4. **Corneal clouding
5. **Hearing loss
6. Enlarged tongue
7. **Valvular heart disease
8. Hepatosplenomegaly
9. ***Umbilical / Inguinal hernia (need to reduce early otherwise later on when develop hepatosplenomegaly will be difficult to operate)
10. Developmental delay
11. Abnormal facial features
Skeletal / Joint symptoms:
1. **Evolving joint contracture without signs of inflammation —> Fixed joint deformity early in life
2. **Cervical spine stenosis / Cord compression
3. **Pectus carinatum
4. **Kyphosis / Scoliosis
5. Bilateral hip dysplasia
6. Genu valgum
7. Waddling gait / Reduced mobility
8. ***Short stature of unknown reason
9. Idiopathic carpal tunnel syndrome
10. Multiple joint pain
Marfan syndrome (From JC122)
Mutation in **FBN1 gene (Fibrillin 1 gene) in chromosome 15 (detected by **DNA sequencing)
—> Loss of docking protein FBN1
—> ***↑ TGFβ signalling
Inheritance: ***Autosomal Dominant
DDx:
- Ehlers-Danlos syndrome
- Loeys-Dietz syndrome (LDS)
- Klinefelter syndrome
Revised ***Ghent criteria of systemic features —> Diagnosis of Marfan syndrome
(Ghent criteria (2010) (Vinson Cheng)
Four major features:
1. Dilated aortic diameter
2. Ectopia lentis
3. Systemic score >7
4. FBN1 mutation
- Family history plus 1 / 2 / 3
- No family history: 1+2 / 1+3 / 1+4)
Clinical features
1. **Arachnodactyly: Wrist + Thumb sign
2. **Pectus carinatum deformity
3. **Ectopia lentis
4. Arm-span-to-height ratio **>=1.05
5. Pes planus (flat foot)
6. ***Dolicocephaly (longer head than normal)
Treatment:
1. **β-blocker: to reduce aortic wall stress
2. **Losartan: TGFβ inhibitor —> more helpful than β-blocker (control in aortic dilation in Marfan)
Klinefelter syndrome (SpC Revision)
- Most common cause of ***hypergonadotropic hypogonadism in male
- Incidence 1 in 500-1000 live male births
- A group of chromosomal disorders with >=1 extra X chromosome added to the normal male karyotype of 46,XY
-
**Eunuchoidal body habitus with sparse body and facial hair, **gynaecomastia, ↑ fat mass, **small testes and penis, ↓ verbal intelligence, with **high gonadotropins,
**testosterone deficiency and **azoospermia - Early introduction of testosterone prevents gynaecomastia
Sotos syndrome (From JC119)
- Most common syndromic cause of congenital macrosomia
- Autosomal dominant
- Deletion / Heterozygous variant of NSD1 at chromosome 5q35
- Family history many reveal an affected parent but most cases are sporadic + de novo
Clinical features:
1. Distinct facial features
- High prominent forehead
- Sparse frontoparietal hair
- Downslanting palpebral fissures
- Small pointed chin
2. Increased birth length
3. Hypotonia
4. Variable large hands and feet
5. Joint laxity, renal abnormalities, cardiac abnormalities
6. Prognathism
7. Learning difficulties (variable) (vs ***No developmental delay in Beckwith-Wiedemann syndrome)
Costello syndrome (From JC119)
- Autosomal dominant
- Heterozygous pathogenic variant in HRAS gene on chromosome 11
- Part of Noonan / CFC (Cardiofaciocutaneous syndrome) / Costello RASopathy spectrum
Clinical features:
- Failure to thrive (NB may present as SGA, IUGR babies; May be LGA, but many have difficulties, develop FFT and short stature later)
- Coarse facial features
—> Thick lip
—> Prominent nose
—> Wide mouth
- Loose folds of extra skin (esp. on hands + feet)
- Sparse curly hair
- Arrhythmia
- Structural heart defects
- Hypertrophic cardiomyopathy
- Later: Significant learning difficulties, increased tumour risk (***Papillomas, Rhabdomyosarcoma, Neuroblastoma, Transitional cell carcinoma)
Klippel-Trenaunay syndrome (From JC119)
- Segmental overgrowth
- Mosaic PIK3CA mutation
Classical triad of:
1. Cutaneous capillary malformation (usually Port-wine stain)
2. Venous malformation / varicosities
3. Soft tissue / Skeletal overgrowth
Complications:
1. Coagulopathy
2. Bleeding tendency
3. Venous insufficiency
4. Limb length discrepancy
5. Kasabach-Merritt syndrome in 50% (Thrombocytopenia)
Cloves syndrome (From JC119)
CLOVES: Congenital lipomatous overgrowth, Vascular malformations, epidermal naevi, scoliosis / skeletal and spinal syndrome
- ~ to Klippel-Trenaunay syndrome —> also caused by somatic PIK3CA mutation
- Progressive + disproportionate segmental overgrowth syndrome involving:
1. Subcutaneous
2. Muscular
3. Vascular
4. Adipose tissue
5. Skeletal overgrowth
