Genetic Syndromes Flashcards
Achondroplasia
Most common skeletal dysplasia - **autosomal dominant **- FGFR3 mutation - 50% sporadic. Generally normal lifespan but risk of cervical cord compression
1:20000
Non-Proportional dwarfism
Limbs: Rhizomelic shortening - upper part of limbs. Trident shaped hands. Ligament laxity. Varus/valgus
Face: Frontal bossing, Small midface with flattened nasal bridge. Dental malocclusion
**Spine **: Kyphosis/lordosis, scoliosis, gibbus
CVS: Pulm HTN from OSA
Ears: OM
Narrow Foramen Magnum - Hydrocephalus
Danger of cervical CC due to narrow foramen magnum =- offer LL neurology for SCC
Tx: orthopaedic - kyphoscoliosis
Neurosurgical - decompress the foramen magnum or shunt hydrocephalus
Near-normal life expectancy if heterozygous
Specialised Growth Charts
Spirometry - reduced lung capacity & OSA
Trisomy 21
Poland Syndrome (unknown aetiology and not heritable)
Radar O Reilly!
Absent pectorals
Short or webbed fingers on ipsilateral side
1:20000 M:F 3:1. R>L
Sx:
GI abnormalities
Abnormalities of pectorals, humerus, ulna, radius
Oligo (missing) or Brachy (short) or Syn (webbed) dactyly
Dextrocardia
Diaphragmatic hernia
Liver/biliary abnormalities
Single palmar crease on same side
Moebius Syndrome
Facial paralysis, unable to move eyes side to side, no eye closing
Underdeveloped 6 and 7th nerve
?Vascular disruption in embryology. Sometimes auto dom
Sx:
Normal intelligence
Poor lateral eye movements
Lack facial expression - facial paralysis
High palate, hypotonic tongue, upper lip retraction
Can have VIII affected -> hearing loss
Talipes, oligodactyly
Strabismus
Potter Sequence
Classic: bilateral renal agenesis
T1: ARPKD
T2: Renal agenesis
T3: ADPKD
Sx:
Oligohydramnios -> compression by uterus -> physical deformities
LL abnormalities - talipes, bowing, sirenomelia (usually fatal)
Parrot beak nose, redundant skin, skin fold from canthus across cheek.
Low ears
GU anomalies, Anal atresia, Atresia of duodenum/colon/oesphagus, Diaphragmatic hernia
Weaver syndrome
**Autosomal dominant **
Rapid growth beginning in the prenatal period
Macrocephaly
Flattened occiput
Long philtrum
Retrognathia
Round face in infancy
Prominent chin crease
Large ears
Strabismus
Hypertelorism
Epicanthal folds
Downslanting palpebral fissures
Loose skin, thin deep-set nails, thin hair, short ribs, limited elbow and knee extension, camptodactyly, and a coarse, low-pitched voice.
Sotos syndrome
Overgrowth and advanced bone age
1:14000
LGA
Elongated Macrocephaly, Down slanting palpebral fissures and a pointed chin.
Hypertelorism, prominent forehead, large hands, feet, ears, nose and genitalia
Intellectual impairment; autistic traits.
Frequent behavioural impairments include ADHD, phobias, OCD, tantrums, and impulsive behaviours.
Vocal: stuttering, difficulty with sound production, or a monotone voice.
Hypotonia -> dev delay
Other signs include scoliosis, seizures, heart or kidney defects, hearing loss, and problems with vision
NSD1 mutation
Turner Syndrome
1:2500
50% due to XO
Hypogonadism & short stature (growth and pubertal failure)
Hands: Cubitus valgus, oedema of hands and feet, hyperconvex nails, short 4th/5th
Head: Webbed neck, low hairline, high arched palate,
Chest: Wide spacing of nipples, shield chest, Cardiac scarring
Chronic OM
CVS: bicuspid aortic, Aortic coarctation, aortic dissection
Gonadal dysgenesis: streak ovaries, amenorrhea, delayed puberty (15% start but delay)
Renal: Congenital renal, HTN, T2DM, Hyperlipidaemia
Learning difficulties
Screening for Abnormalities - Thyroid
GH replacement
Oestrogen/progesterone replacement - Pubertal staging
School support
Noonan Syndrome
Auto Dom
1:1000-2500
Mean IQ 85
30%: Coag defects - vW, low plt, Factors abnormal
Short
Facies: hypertelorism, epicanthic fold, ptosis, micrognathia, low-set and posteriorly rotated ears, depp philtrum, small upturned nose
Chest: widely spaced nipples, cubitus valgus, pubertal delay
CHD: Pulmonary stenosis, ASD, VSD, HOCM
Cryptorchidism, herniae
Russell-Silver
1:75000
Uniparental disomy of Chr 7 and defect on Chr 11
Relative macrocephaly (Normal HC). IUGR -> SGA. Poor growth
Limb: hemi-hypertrophy, clinodactyly, camptodactyly, toe syndactyly
Head: triangular face with high forehead and micrognathia, relatively large head, blue sclera, prominent nasal bridge, late closure of AF, short and webbed neck (Sprengel’s deformity)
Hypospadias or undescended testes
Hypoglycaemia & feeding difficulties
Denys-DRASH or DRASH syndrome
Abnormality in the WT1 gene
Triad:
1. Pseudohermaphroditism
2. Mesangial renal sclerosis
3. Wilms’ tumor.
Early nephrotic syndrome -> mesangial renal sclerosis -> kidney failure usually before 3y
SX: loss of playfulness, decreased appetite, weight loss, growth delay, abnormal skeletal development, insomnia, abdominal pain, constipation, and anuria.
WAGR syndrome
Wilms tumour
Aniridia
Genitourinary anomalies (Gonadoblastoma)
Mental Retardation
Mutation on chromosome 11 in the microdeletion of 11p13 - FISH (fluorescent in situ hybridization)
Mx:
Regular kidney surveillance for Wilms’ tumour until at 6–8 y
Thereafter follow-up of late onset nephropathy
Females may have streak ovaries, increase the risk of gonadoblastoma
Beckwith Wiedemann
Foetal overgrowth
1:14000
Most sporadic, some Auto Dom
3 Major or 2 major & 3 minor:
Major
1. Pre or postnatal overgrowth
2. Macroglossia
3. Abdominal wall defects
Minor
* Ear lobe creases or posterior helical pits
* Facial naevus flammus
* Hypoglycaemia
* Organomegaly
* Hemihypertrophy (25%)
Higher likelihood of prematurity. Commonly hypoglycaemia. Some req diazoxide. CHD in <10%.
Tongue -> feeding problems, OSA, speech problems
Overgrowth associated with advanced bone age
Neoplasia in 5-10% - commonly Wilm’s, then adrenocortical carcinoma, hepatoblasoma, neuroblastoma - higher risk in hemihypertrophy
Learning difficulties - NN hypoglycaemia
Mx:
* AFP monitor to 4 y
* Reg USS until 8 yrs
By adolescence can lead a normal life if no sequalae of hypoglycaemia
Prader Willi
Lack of active 15q11-q13. The genes in the PWS region are normally only active on the paternal chromosome
Dysfunction of hypothalamus
- Hypotonic - weak cry or suck
- Failure to thrive
- Unregulated appetite (hyperphagia)
- Learning disabilities
- Growth hormone deficiency/short stature,
- Small hands and feet, narrow forehead, light skin & hair
- Scoliosis
- Sleep disturbances with excessive daytime sleepiness
- Speech apraxia/dyspraxia
- OCD symptoms, skin picking, and labile emotions
Cornelia de Lange
Spontaneous genetic mutations
Slow growth pre & post birth -> short stature
* Intellectual disability
* Abnormalities of bones in the arms, hands, and fingers
* Hypertrichosis
* Microcephaly
* Hearing loss
* GI issues
* CLP
Facies: arched eyebrows often meet in the middle (synophrys), long eyelashes, low-set ears, small and widely spaced teeth, small and upturned nose
Social interaction issues
