Short cases Flashcards
Short stature
Introduce Wash hands General Inspection with adequate exposure • Dysmorphic • Disproportionate stature • Tanner staging • Nutritional status • Skeletal abnormalities • Colour/inc RR/Skin
Measurements and manoeuvres:
A) MEASUREMENTS:
Height
Lower Segment from pubic symphysis
Calculate Upper segment (Ht-LS)
US:LS Birth 1.7, 3yrs 1.3, 8+ yrs 1.0
If high = short lower limbs (skeletal dysplasias, ↓Th)
If low = short trunk (vertebral irradiation, scoliosis) or a short
Neck (Klippel Feil syndrome)
Arm span 0-7 -3cms, 8-12yrs 0, 14yrs +1 in ♀
HC
Weight
Plot on Centile chart
Ask for birth measurements
Ask for parental percentiles and ages at puberty
B) HANDS AND FEET TOGETHER:
Asymmetry (Russell-Silver)
Approximation of shoulders (absent clavicles in cleidocranial dysostosis)
C) ARMS OUT STRAIGHT:
Cubitus valgus in Turner’s and Noonan’s >15˚ in ♀ and >10˚ in ♂
D) THUMBS ON SHOULDERS:
Proximal segment shortening – achondroplasia, hypochondroplasia
Middle segment shortening
Distal segment shortening – acromesomelic dysplasia
E) PALMS UP:
Simian Crease – T21, Seckel’s
Clinodactyly - Russell-Silver, T21, Seckel’s
F) MAKE A FIST:
Short 4th metacarpal – 45XO, FAS, Pseudohypoparathyroidism
G) BACK:
Short neck - Klippel-Feil, Noonan’s
Web neck - 45XO, Noonan’s
Low hairline - 45XO, Noonan’s, Klippel-Feil
H) TOUCH TOES:
Scoliosis - Noonan’s, Klippel-Feil
SYSTEMATIC EXAMINATION:
Investigations:
Blood:
FBC and Film Ch disease, anaemia
ESR IBD
U+E’s, Cr Ch renal disease
Fasting Glc DM
Ca, PO4, Alk Phos Ricketts, hypophosphatasia
LFT’s CLD, nutritional deficiency
TTG Abs Coeliac
Pancreatic isoamylase Shwachman’s
TFTs, TSH Hypothyroidism
Karyotype 45Xo, T21
Somatomedin C Decreased GH def, coeliac, Crohn’s, malnutrition, DM (poorly controlled)
GH stimulation tests GH deficiency
(insulin, GHRH, exercise, Clonidine)
LH, FSH, prolactin, Hypogonadism
oestradiol, testosterone
Dex Suppression Test Cushing’s syndrome
Sweat:
Sweat conductivity CF
Imaging: Bone age Maturational delay, precocious puberty, ↓Th, ↓pit Skeletal survey Skeletal dysplasias Skull X/R Craniopharyngioma CT/MRI Brain Intracranial tumour
Bronchiectasis 7 causes
CF REcurrent infections / aspiration Severe pneumonia / infection (adenovirus) Immune deficiency PCD Foreign body Congenital anomaly
Steroid side effects
MEDICHOG
Myopathy Eyes - cataracts Diabetes Immune suppression Cushingoid Hypertension Obesity / Osteoporosis Growth suppression
Ataxia Ddx
Cerebellar
- Malformation (dandywalker)
- infection
- tumour
- cerebrovascular event
- Degenerative / demyelinating disease
Vestibular - labyrinthitis
Peripheral neuropathy - HSMN ; B12/folate def Ataxia telangiectasia Friedreichs ataxia Guillan barre Hypothyroid
Examine
Gait, upper and lower limb neuro
Eyes, speech ; ears
Abdo
Cafe au lait Ddx
NF1 Fanconi anaemia Russel silver Noonans / LEOPARD Bloom syndrome
Short stature exam
Inspection - dysmorphic, proportional, nutritional, evidence of chronic disease
Growth parameters
US:LS measurement
Arm span
Manoeuvres Hands together Hand out - carrying angle thumbs to shoulder palms up and palms down make a fist hands out inspect back, touch toes
Mention
Symmetrical / asymmetrical
syndromal or not
pubertal status
Inx Bone age Karyotype / microarray Screen for chronic disease Endocrine screen - IGF1, GH stim ; TFT ; LH/FSH, prolactin, ACTH, Dex supposed ? skeletal survey
short stature clues to diagnosis
IS NICE
Syndromic
- normal weight: Turners, Noonans, Russel silver, Kallman
- Fat: PWS, T21, Bardet Biedl, Alstrom
Disproportionate short stature
- Skeletal dysplasia
- short limbs: achondroplasia
- short neck/spine: Klippel feel, OI, scoliosis, RT
Short but thin - think chronic disease
1. Idiopathic: Constitutional or familial short
2. Intrauterine: TORCH, SGA, FASD
3. Nutritional: Deprivation or malabsoprtion
4, Iatrogenic: Radiation
5, Chronic disease: CKD, CF, IBD, malig
6. Psychological: AN
Short and fat
1. Endocrine: Hypothyroid, Hypopit, Cushing, PseudohypoPTH
2, Steroids
Short stature Ddx
IS NICES
Idiopathic - familial / constutional
Skeletal - dysplasia, scoloisis
Nutrition
Iatrogenic - steroids, radiation
Chronic disease - CF, coeliac, cardiac, renal, IBD
Endocrine - Hypothyroid, hypo pit, GH def, PseudohypoPTH, cushings ; delayed/precoc puberty
Syndromic - turner, Noonan, PWS, T21, FASD, russel silver
Tall stature Ddx
FES
Familial - constitutional or obesity
Endocrine: Hyperthyroid, precocious puberty (central/peripheral), Pituitary gigantism
Syndromic
- Marfans, NF1, Homocytinuria, Sotos, Klinefelters, BWS, Kallmans
Causes of obesity
- Nutrition
- Endocrine - Cushing, hypothalamic, hypothyroid
- Syndromic: PWS, Bardet bide, Altrom, Kallman, klinefelter
- Steroid induced
Complications of obesity
Low mood / bullying HTN/Dyslipidemia/T2DM (metabolic) OSA SUFE Fatty liver Precocious puberty
Causes of a goitre
- Autoimmune thyroiditis
- Graves disease
- Simple goitre (normal TFTs and no Abs)
- Hyperplasia
- Diffuse nodular non toxic goitre
- Subacute thyroiditis
- Malignancy
- Infiltration
Most common worldwide is endemic goitre secondary to iodine deficiency
Short stature investigations
Bone age
Screen for chronic disease - FBC, U&E, LFTs, TFTs, HbA1c, coeliac serology ; ESR, CRP IGF-1 and GH stimulation test Endo: LH/FSH/testosterone/oestradiol ? ACTH / dex supp test Urine P:Cr ration Stool: calprotectin, steatocrit Sweat test
Genetics: microarray or karyotype
Skeletal survey if ? skeletal dysplasia
MRI brain
Tall stature investigations
Bone age XR (precocious puberty) Urine methionine (homocystinuria) Karyotype / gene panel ECHO Bloods: TFTs, Renal, LFT, FBC, prolactin/LH/FSH/ACTH MRI brain
Bone XR ? osseous dysplasia (McCune Albright)
ejection systolic murmur LUSE
RVOT - subvalvular/valvular(noonans has dysplastic valve) / supravalvular (Williams ; branch PAS Alagille) - all heard loudest LUSE radiating to back (branch stenosis to axilla)
If to/fro murmur suggestive PR (post TOF repair)
PS - radiates to back ; RVH ECG (RBBB if TOF)
ASD - fixed splitting S2 ; RBBB (RSR) ECG
AVSD - superior axis
ejection systolic murmur RUSE
LVOT - subvalvular(HOCM), valvular, supravalvular(williams) ; distal (aortic arch obstruction, radiation to back (inter scapular). Loudest RUSE radiates to neck
AS - radiates carotids
- supravalvular/valvular/subvalvular
- suprasternal thrill
ECG LVH +/- strain
Holosystolic murmur
Apex
- MR (congenital, acquired - post RHD, DCM/ALCAPA)
ECG bifid p waves, LVH
LLSE
- VSD (biventricular hypertrophy ; canal VSD assoc w/ AR)
- coarctation
RLSE - TR/ebsteins
Continuous
PDA (bounding pulses) - loudest left infraclavicular ; if large can be associated with heart failure.
ECG LVH or wide bifid p waves
BT shunt (look for scar)
Ddx
- venous hum (turn neck, goes away)
- Aortopulmonary window
Diastolic murmurs
LSE -relative TS in ASD(mid diastolic)
Apex - relative MS in VSD (mid diastolic)
LUSE PR post PS/RVOT surgery
- post tet repair
RUSE - AR ( congenital associated with bicuspid AV, turners, conal CCSD ; Acquired - RHD, post op) ; severity associated with collapsing pulses and wide pulse pressure.
rate out of 4
Cardiac scars
Midline sternotomy
- Cardiac transplant
- complex cardiac lesion
- valve replacement
Lateral thoracotomy
- Shunt surgery or PDA closure
- PA banding
- ASD/VSD closure
Dextrocardia ECG
q waves in I and AVL
Large R waves V2,V3
R wave regression
Cause of hepatomegaly
SHIRT x 2
Structural - biliary atresia, choledochal cyst, Alagilles (bile duct paucity)
Storage : metabolic (Gaucher, nieman pick, GSD) Wilsons, A1AT, CF
Haematoligical - thalassemia, SCD, leukaemia ; NHL
Heart - CCF (R sided F)
Infection - Viral: CMV/EBV, hepatitis ;
Inflamm - IBD, hepatitis
Infiltrative - LCH, sarcoidosis
Rheum - sJIA, SLE
Tumours
Hepatoblastoma, HCC
Trauma - haematoma
SPLENOMEGALY
HIP
Haematological - HS(AS); G6PD (XLR)
Infective - SBE, Typhoid
Portal HTN
Heptosplenomegaly Ddx
CHIMPS
Connective tissue - SLE, JIA Haem: Thalassemia, Sickle cell, leukaemia, lymphoma Infection - CMV/EBV/Hepatitis Metabolic - Gaucher, pieman pick Portal HTN
Enlarged kidney
CHARTS
Cystic (ADPKD, ARPKD) Hydronephrosis Adrenal Renal V thombosis Tumour - wilms, neuroblastoma, RCC
Clubbing differential
Cardiac - cyanotic
Resp: Suppurative lung disease - CF, bronchiectasis
Gastro - CLD, IBD
Thryoid - acropachy (hyperthyroid)
Portal HTN
Splenomegaly
Portosystemic shunts - varices, haemorrhoids, caput medusae
Ascites, low albumin
Causes
- Pre hepatic- portal V thrombosis
- Heptatic: cirrhosis, A1AT, CF, Biliary atresia, neonatal hepatitis, VOD
- Post hepatic: Budd chiari (hepatic V obstruction), constrictive pericarditis
Bronchiectasis - 7 causes
CF Recurrent infections/aspirations Severe pneumonia (TB, adenovirus) Immune deficiency Primary ciliary dyskinesia Foreign body Congenital airway anomaly
Cerebellar exam
DANISH
Dysdiadokinesis Ataxia Nystagmus Intention tremor / past pointing Speech Hypotonia
Cerebellar signs are ipsilateral to side of lesion
Hemihypertrophy
Ddx and exam
simple - unilateral enlargement of one limb
complex- 1/2 body enlarged
- Beckwith - Wiedman
- Russel silver (hemihypoplasia)
- Klippel - trenaunay weber (triad of vascular malformation - venous malformation, abnormal lymphatics, - more localised)
- NF1
- Isolated hemiherplasia - assoc wilms
- Proteus syndrome
Exam
Look for birthmarks, vascular malformation, CALM
Growth (short -RSS, tall - BWS)
Associated tumours - Wilms, hepatoblastoma, gonadal, neuroblastoma (with BWS)
Neuro - hemiatrophy in hemiplegic CP ; Gait
Hands and feet together, touch toes (scoliosis), palms exposed. Check growth, HC, weight, BP
BWS
- overgrowth, methylation defect 11p15.5
- macroglossia, hemihypertophy, omphalocoele, hypoglycemia (secondary hypperinsulinism)
- Naevus flammus forehead, abnormal ear helix and crease. Cardiomegaly
- Risk tumours (films, hepatoblastoma, GCT, neuroblastoma)
- US surveillance every 3/12 until 8 in high risk
RSS
- small stature, triangular face, apparent macrocephaly, blue sclera, 5th finger clinodactyly, hemiatrophy
Risk Wilms ; UPD Ch7 in 10%
Cafe au lait macules
Oncology long case
Hx diagnosis - initial symptoms, treatment, complications of treatment ; parents attitude to diagnosis
Parental understanding of prognosis
Impact on family, siblings, marriage, finances
Current status
- how long post treatment ; central line
- complications - infections, anaemia
- prophylaxis and compliance ; mouth cares
- SE from treatment
- Infections : VZIG within 96hours VZV, IVIG for measles
- Impact ADL
- Growth and development
- School
- Immunisation status, any immumnosuppresives
Late effects and GVHD
Late effects
- short stature (RT, hypo pit, hypothyroid)
- Eyes - cataracts (TBI, steroid)
- Ears - hearing impairment (RT, cisplat, gentamicin)
- Steroid SE and metabolic syndrome
- Psychological - mood, memory, attention, IQ
- Puberty
- Fertility - any fertility preserving measures
- Cardiac (anthracyclines, RT ; use dexrozoxane ; regular ECHO)
- Bone health
- Peripheral neuropathy (vincristine)
- Secondary tumours - RT, alkylating agents, etoposide
Social issues, school issues
Hypopituitary causes
Congenital
- midline defect (holoprosencephaly),
-SOD (sept-optic dysplasia) - triad of 1. optic nerve hypoplasia, 2. pituitary hypoplasia, 3. midline brain abnormalities (absent septum pellucid and agenesis corpus callosum).
Mostly sporadic ; Neuro compl, endo comp
wandering nystagmus, visual impoairment
Assoc obesity, temp instability, OSA, ASD
- genetic (CHARGE - CHD7 mutation, PROP1 mutation, Kallman)
Later / acquired
- craniopharyngioma: triad 1. endocrine hypofunction - (growth F, hypothyroid, DI), 2. eyes (bitemporal hemianopia), 3. headache
Rx transphenoidal surgery, RT (become panhypopit post Rx)
- cranial RT, (affects anterior pit)
- trauma (TBI)
Hypopit Hx
- Diagnosis, complications, treatment
- cognition, development and school
- growth and puberty
- learning / behaviour issues
- Vision
- Neuro symptoms (SOD, holopros)
symptom screen for each pituitary hormone
Impact Education, treatment Management Hypos Emergency steroid plan, stress dose - IV hydrocortisone, IV fluid bolus + IV dextrose - increase steroid if taking P450 inducers and during pregnancy Management DI (DDAVP, monitor Na) Puberty and growth - GH treatment - Pubertal induction treatment males testosterone IM monthly girls - oestrogen Micropenis treat with testosterone
Rx with glucocorticoids before thyroxine (risk causing adrenal crisis)
T21 long case
Prenatal screening (detects cell free fetal DNA/RNA in maternal blood)
non disjunction trisomy 21 in 95% ;
3-4% Ch 14/21 translocation (robertsonian) - recurrence risk 12% if mum carrier, 1% if dad carrier
2% mosaic
Hx
Diagnosis, symptoms at birth, initial issues (Resp, feeding, CVS), any gut/surgical issues
Initial investigations ; genetic counselling; Karyotype
Treatments: Surgical / medical
Hospitalisations / complications
Impact on child - school, ADLs, school funding
Impact family - financial, further kids, guardianship
Cardiac - 30-50% cardiac issues. ECHO birth + 6 weeks
AVSD (45%), VSD (35%), ASD PDA, TOF
Echo ; risk of pulmonary HTN ++ (early surgical repair)
If unrepaired CHD - risk CVA and brain abscess.
Adults may get mitral valve prolapse and AR even if no history CHD
Subtle immune deficiency - recurrent URTI/LRTI
Predisposed to autoimmune conditions
- hypothyroidism (15% DS) ; congenital hypothyroid 1/140
- coeliac disease (5-7%)
- DM, malignancies (leukaemia)
Chronic OME, dental issues
Joint and MSK issues
15% AAI due to excessive mobility of C1 on C2, only 2% symptomatic as result subluxation / cord compression - neck pain, new continence issues, difficulty walking/weakness
Hip instability 1-7%
Foot issues
Hearing - 50-80% hearing loss, CHL, SNHL, mixed
chronic OME ++ common, grommets, T/As
SLT for hearing aids
Eyes/vision
50% ocular impairment - refractive errors, strabismus, nystagmus, cataracts.
Cognition and development
delay gross motor milestones due to hypotonia and joint laxity, average walking 2-4years
Most have mild (IQ50-70) - Mod (35-50) ID (average developmental age 5.5)
Language milestones slower to develop than others
Neurodevelopmental issues
ADHD (6%), Aggressive / oppositional behaviour
ASD dual diagnosis (7%)
seizures (8% - 2 peaks, 1st year life, in 20s)
75% alzheimers by >60yrs
Depression (outrule hypothyroid)
Growth and weight
High risk obesity
Dental
Hypothyroid
Haematological
- Neonates - polycythemia and macrocytosis
- transient myeloprolif in 10% (regress by 2-3months, mutation GATA1, 20% with TAS will develop AML in first 4 years life
-Leukaemia (15-20x increased risk)
AML and ALL (1/300) - better outcome for AML in DS
Chemo sensitive, dose reduce
GI - 7% GI defects ; Hirscsprung, duodenal atresia
Coeliac
Skin - palmoplantar hyperkeratosis 40%
Adolescents 50% keratosis pillars (follicular rash)
fungal skin infections
ECG criteria for LVH and RVH
54321 rule
RVH
RV1: >5squares <1mo ; >4squares <1year ; >3squares >1yo
SV6: >3sq <1mo ; >2sq <1yo ; >1sq >1yo
Also RAD, upright T V1 ; qR V1
LVH:
RV6: >3sq <1mo, >4sq <1yo, >5sq>1yo
SV1: >1sq <1mo, >2sq <1yo ; >3sq>1yo
Also LAD, flat/inverted T waves I/AVF
Complications CHD
Cyanosis - growth/puberty/acne/exercise
Complications surgery
- shunts: malfunction, protein losing enteropathy (Fontana)
- Stenosis / regurgitation / CHF / heart block
- Operative issues: RLN palsy, Horners, diaphragm issues
CNS complications - stroke (SBE/post op/ polycthemia)
Drug complications: Anticoags
COMPLICATIONS FONTAN
Chylothorax and pleural effusions
Protein losing enteropathy
Stroke
Cerebral abscess
Ataxia Ddx
- Cerebellar
Congenital:
- Structural: Dandy walker malformation, chair
- spinocerebellar degenerative: AT, FA(Freidreichs ataxia)
- Metabolic ; other degenerate
Acquired
- Infectious; Acute cerebellar ataxia (post VZV) ; Miller fisher GBS
- Toxins: Alcohol, phenytoin
- Tumours: Medulloblastoma, neuroblastoma
- Stroke / migraine / seizures
- Vestibular: acute labyrinthitis (middle ear infection)
- Posterior column loss
- Subacute combined degenerative cord (B12 def ; absent ankle jerk, dorsal column loss)
- Ataxia telangiectasia
- DM, hypothyroid
4. Peripheral neuropathy (DAM IT BICH) Drugs (vincristine) ; Alcohol Metabolic (DM, CRF) Infective (GBS), tumour, B12 def ; Idiopathic CTD (SLE), Hereditary (HSMN)
Gait short exam
Observation
Looks at shoes - any wearing, any AFOs
Inspection legs (WANGP) wasting/fascicultations ; abnormal movements ; neurocutaneous stigmata, growth arrest, posturing
Any deformities or scars
Spine for scoliosis and scars
Review gait walk normal, heel to toe ; turn quickly walk on toes(S1) ; walk on heel(L5) FOG test (unmask hemiplegia) Run Squat
Romberg - +ve eyes open - cerebellar ;
+ve eyes closed (propricoptive loss)
Check for pronator drift
Squatting, towers, leg length discrepancy
Clubbing Ddx
Cardiac - cyanotic cardiac disease
Resp - suppurative lung disease (CF, bronchiectasis, PCD)
GI - CLD, IBD
Thyroid - thyroid acropachy (hyperthyroid)
Complications splenomegaly
hypersplenism - thrombocytopenia
function asplenism - susceptible encapsulated organisms
splenic infarction (SCD) - painful
Early satiety / reduced appetite
NF1 diagnosis criteria
CALNOP
Cafe au lait >6 Axillary/inguinal freckling Lisch nodules (2+) / Long bone dysplasia Neurofibromas (2+) Optic pathway glioma Plexiform neurofibroma (1+)
Others
First degree relative
Distinctive osseous besoin - sphenoid wing dysplasia
Short case NF1
Complications
- Skin CAL
- Tumours - optic glioma, plexiform neuro (MPNST)
- bones - dysplasia , scoliosis
- Growth - short stature, macrocephaly, precocious puberty
- Seizures
- HTN (idiopathic, renal artery stenosis, phaeo)
- Developmental delay
eye exam short
Inspection - front/above/side
- any neurocutaneous stigmata, HC, dysmorphic, ptosis (congenital vs acquired)
Lids/iris / lens - glaucoma/cataract
Squint
- Heterophoria (latent squint - when tired)
- Heterotropia ( permanent squint)
- ESO (convergent), EXO (divergent)
- Paralytic ( related to issue EOM weakness/CN palsy)
- non paralytic
If concern hyperthyroidism - lid lag
Visual acuity - infant toy, preschool E chart, school - snellen External eye movements Ptosis Visual fields - bitemporal hemianopia - pituitary / optic chiasm - homonymous hemianopia - optic tract - upper quadrant - temporal - Lower quadrant - parietal Convergence Pupils and Pupillary reflex Fundoscopy / red reflex
Gait exam short
Inspection ; - spine/scoliosis - asymmetry /hemihypertropyh / leg length discrep Gait - normal - heel-toe (from 5 yrs) - up on toes (S1) - up on heels (L5) FOG test (walk outside of feet) - unmask hemiplegia Run Rombergs - eyes open (cerebellar) - eyes closed (posterior column) Squat (prox weakness) / Gowers Neuro exam
Internuclear ophthalmoplegia
impairment of lateral conjugate gaze ; get failure of adduction in affected eye and contralateral eye abducts with nystagmus
if right eye affected, get diplopia on looking left
Caused by lesion in medial longitudinal fasciculus
Seen in MS, stroke
Ptosis Ddx
impairment of levator palpebral superioris
Horners (ptosis/meiosis/annhydrosis)
Large pupil - CN3 palsy (tumour, vasc, MS)
bilateral with fatigue - NMJ disorder (MG)
Bilateral facial weakness Ddx
Brainstem - vascular, tumour, möbius, demyelination Posterior fossa - acoustic neuroma Cranial nerve - GBS, bells, Ramsay hunt NMJ - MG, botulinism Muscle - MD, FSHD, myopathy
Moebius - CN 6 and 7 palsy
CN palsy investigations - MRI brain/spine ; LP
NF1 diagnostic criteria
CALNOPOF
2+ of the below
- CAL macules (6 or more) >5mm prepubertal or >15mm post pubertal
- Axillary or inguinal freckling (age 5-8)
- Lisch nodules (2+, usually appear 5-10years ; all adults)
- Neurofibroma (2+) or 1+plexiform neurofibroma
- Optic Pathway glioma (15-20% NF1, mostly <7years ; most asymptomatic, Rx chemo Carboplat and vinc)
- Plexiform neurofibroma - seen 50%, (risk progression to MPNST)
- distinctive Osseous lesion - sphenoid wing dysplasia, long bone bowing with pseudoarthosis
- First degree relative with NF1
Genetics - Autosomal dominant ; Ch 17q11.2 ; germline mutation in NF1 suppressor gene, codes for neurofibrin (negative regulator of RAS protoncogene - controls cell growth)
1:3500 people
50% patients have no family history (de novo)
Clinical diagnosis, rarely need genetic diagnosis
Complete gene deletion - poorer prognosis
Complications NF1
- Tumours
- Hypertension - renal vascular disease, renal artery stenosis Coarctation, phaeo
- Scoliosis - appears 6-10yrs
- MPNST - adolesence (PET scan), 10%
- Malignancy risk (7xleukaemia risk,
- Pulmonary valve stenosis
- Vasculopathy - moyamoa
- IQ and behaviour - 30% ASD features,
NF1 long
Hx - cognition and development ; speech/hearing
School Hx ; behaviour
Vision / opthal reviews
Growth and centiles, puberty. Asymmetry (whole gene)
Neurofibromas and Rx ; skin
MSK - bone, scoliosis
HTN - cause and Rx ; vasculopathy / Neuro symptoms
Cardiac - PS, HOCM
Monitoring Skin Vision - OPG highest risk <6 ; 15% have OPG Learning and behaviour, development Self esteem Scoliosis and osetoporosis HTN - renal US and 24hr urine catecholamine Genetic counselling (AD)
Sturge weber
Somatic mutation GNAQ, gain function mutation
Triad - PWS V1, leptomeningeal angiomas, glaucoma
Complications Stroke like episodes / hemiplegia Epilepsy, developmental delay Glaucoma (2/3 have congenital glaucoma) - risk lifelong, Cognitive impairment in 80% (50% ID) Behaviour and emotional issues Migraines / headaches Body asymmetry - hemihyperplasia (overlap with KTW) Endo: central hypothyroid, GH deficiency
Mx Seizures - AED PWS - pulsed dye laser Aspirin to reduce risk stroke Glaucoma Rx
Tuberous sclerosis aetiology
Multisystem disorder, characterised by tumor like growths (hamartomas) in multiple organs
• Incidence: 1 in 5800
• Dominantly transmitted ; High incidence of spontaneous new mutations (up to 75%)
Two genes associated
• TSC1 – 9q34 – hamartin (20%)
• TSC2 – 16p13 – tuberin (60%)
• TSC2 more severe phenotype but considerable overlap
Loss MTOR inhibition - cell growth/proliferation
TS surveillance
• Genetics: Genetic testing and family counseling
• Brain
– SEGA monitoring
• MRI of brain every 1-3 years in asymptomatic <25y
• Those with large/growing SEGA more freq
• Educate re signs of raised ICP
• Surgical resection for acutely symptomatic SEGA
• Surgical or Medical treatment (mTOR inhbitors) for growing but asymptomatic SEGA
– Screen for TSC associated neuropsychiatric disorders
• Implement evidenced based management for autism/ADHD/anxiety
• Sudden change in behaviour think SEGA/seizure/renal disease
– Epilepsy
• Obtain routine EEG in all with known or suspected seizures. Vigabatrin first-line for spasms
• Established antiepileptics as per epilepsy of any cause for other seizure types
• Epilepsy surgery should be considered for medically refractory epilepsy
• Kidney
– Obtain MRI abdomen to assess for progression of angiomyolipomas and renal cystic disease every 1-3 years
– Assess renal function and BP annually
– Embolisation followed by corticosteroids first line for angiomyolipoma presenting with acute haemorrhage. Avoid nephrectomy.
– Asymptomatic, growing angiomyolipoma >3cm treat with mTOR inhibitor, selective embolisation second line
• Lung
– Clinical screening for LAM (exertional dyspnea)
– Lung function tests and 6 minute walk test for females 18y+, males if symptomatic
– Counsel regarding smoking and estrogen risks
– HRCT every 5-10 years in asymptomatic
– Those with lung cysts – annual pulmonary function and HRCT 2-3 yearly
– mTOR inhibitors for mod-severe lung disease or rapid progression
– Are candidates for lung transplant
• Skin
– Exam annually
– Disfiguring lesions Rx with surgical excision/ laser/topical mTOR inhibitors
• Teeth
– Detailed dental review every six months
– Panoramic radiographs by 7 years
– Symptomatic / deforming lesions treated
• Heart
– ECHO every 1-3 years until regression documented
– ECG every 3-5 years
• Eyes
– Annual eye exam in those with identified lesions or visual symptoms at baseline
– Periodic examination if on Vigabatrin treatment
Diagnostic criteria TS
Genetic diagnosis
Clinical diagnosis - 2 major or 1 major and 2 minor
Major criteria 4 brain - SEGA, - SENA, - cortical dysplasia -multiple retinal hamartomas 4 skin - SHAU - Shagreen ptaches (50%, first decade) - hypomelanocytic macule >3 which are >5mm - birth on - Angiofibromas >3 (age 2-5yrs, >75%) - Ungal fibroma >2 (adolescence) 3 others - lung/heart/kidney - LAM - women in 30s, HRCT and 6min walk test - Renal Angiomyolipoma - Cardiac rhabdomyomas
Minor • Confetti skin lesions • Dental pits (>3) • Gingival fibromas (≥2) • Retinal achromic patch • Multiple renal cysts • Non-renal hamartomas
Hx in TS
Diagnosis, genetics Seizures Cognition, learning Development Behaviour Cardiac Eyes / Lung / Renal If on Vigabatrin need eye screen SE Everolimus - elevated cholesterol & TG, transaminitis, leucopenia. Therapeutic monitoring Interacts with AEDS - P450 inducers (carbamazepine) decrease levels.
NF1 annual surveillance
Parents must be examined and educated regarding risk to future pregnancies
Age 0–8 years:
• Annual examination for long bone bowing, asymmetry, scoliosis, hypertension
• Developmental, growth and head circumference assessment
• Annual pediatric ophthalmologist examination
Age 8–15 years:
• Examination looking for scoliosis, limb asymmetry, neurofibromas
• Review school performance looking for learning disabilities and
attention deficit and psychosocial evaluation
• Discuss NF and the affect of puberty on NF
Age 16–21 years:
• Examination for neurofibromas. Imaging studies to evaluate any complaints of pain
• Review knowledge of NF, school performance, socialization, and self-esteem
• Discuss inheritance of NF1, and risk for pregnancy
• Discuss the effects of puberty, pregnancy, and birth control pills
on NF
Age >21 years:
• Examination, blood pressure check
• Imaging studies to evaluate any complaint of pain
• Discuss cutaneous neurofibromas, pain, and the risk of cancer
• Discuss socialization, and career/jobs
Ataxia telangiectasia
AR, mutation ATM gene
AFP raised
- Ataxia / cerebellar dysfunction (onset usually 1-4yrs)
- Oculomotor apraxia
- Telangiectasias: Sclerae & sun-exposed area’s such as ears and nose (age 3-10)
- Primary Immune Deficiency
▪ Sinopulmonary infections
▪ Pulmonary Disease: Bronchiectasis and ILD - Cancer Predisposition
▪ Leukaemia (T-cell ALL and T-PLL) and lymphoma - Insulin-resistant diabetes
Nystagmus short
Unilateral nystagmus - Needs MRI to outrun tumour
INO - failure adduction affected eye with nystagmus of abducting eye. Due to pathology in brainstem affecting medial longitudinal fasciculus
Describe
- Pendular (same velocity each direction)
- Jerk (quicker in one direction - slower movement represents the pathology)
- Horizontal/verticular
Congenital nystagmus
- related to visual conditions, usually bilateral, conjugate and horizontal
Acquired
- Cerebellar
- Labryinthine
- Medications
Peripheral - pointed same direction, resolves with fixation
Central - change direction with change gaze, no change with fixation
Spasmus nutans (infants 4mo-3years) - head nodding, nystagmus, head tilt
Floppy infant Ddx
Central (Floppy strong) - UMN disorder
- Hypotonic CP (HIE) ; TORCH
- Brain malformation
- Syndrome - T21, PWS
- Metabolic - smith lemli optik, zellweger
Peripheral (Floppy weak)
- Anterior horn - SMA
- NMJ - congenital MG
- Muscle - congenital myopathy, myotonic dystrophy
Hemiplegia aetiology
Ischaemic stroke
- Cerebral arteriopathies (50-70%)
- Cardiac causes
- Thrombophilia
- Sickle cell
- sepsis
Haemorrhagic
- Vascular abnormalities - AVM, aneurysm
Compliance and adherence methods
Identify barriers
- SEs / complications
- Education
- Simplify regime, involve child, avoid school meds
- Reminders
- Positive reinforcement, negotiate short term goals
- Increase adolescents autonomy over health
- written and oral instructions
Complications growth hormone treatment
Benign intracranial hypertension Type 2 DM OSA Increased risk malignancy Worsening scoliosis SUFE
Indications GH treatment
GH deficiency - proven on 2 bloods \+ GH stim test abnormal (GH<5 on 2+ tests), height velocity <25th centile, normal bone age (<14girls, <16 boys) image pituitary, outule malignancy
Aim: height V >50th centile or increase >2cm per year, bone age<14 girls, <16boys
Short stature without GH def:
height <3sd below mean height age
height velocity <25th centile
no chronic disease, no skeletal dysplasia, no malig
Renal failure (height <2sd below mean, HV <25thcentile)
Turners (monitor and rx hypothyroidism)
Prader willi - outrage OSA, obesity and T2dm, be >2yrs
Other
following pituitary surgery (tumour resection)
- IGF >1sd below mean, GH def, low QOL
Ddx Hypopit
CCRASH
Craniopharyngioma
- endocrine hypofunction, headache, VFD: bitemporal hemianopia
CHARGE - AD, CHD7 mutation
Radiotherapy
Acquired brain injury (including HIE)
Septo-optic dysplasia- Triad of
1. ON hypoplasia, - blindness (wandering nystagmus)
2. Hypoplasia pituitary, (def GH>TSH>ACTH>GnRH>DI)
3. Midline brain abnormal (absent septum pellucidum, genesis corpus callosum)
Others assoc: OSA, ASD, obesity, temp instability
Holoprosencephaly (malformation forebrain)
Order of hormones affected
GH ; TSH ; ACTH ; GnRH
Replace glucocorticoid before thyroid hormone as risk adrenal crisis
Tall stature exam
Inspection Cognition US:LS - elevated in Marfans, klinefelters along with wing span Symmetry ; tanner staging Scoliosis Wrist/thumb sign - Marfans Beighton score if hypermobility Mention split lamp for lens dislocation BP
T1DM complications
Microvascular
- Retinopathy (and cataracts) - screen annual from 12yrs)
- Nephropathy (screen with UACR), monitor BP
- Neuropathy - foot sensation)
Macrovascular - CAD, peripher Vase disease
Assoc Coeliac (3-5%) Autoimmune thyroid (hashimotos ; hypothyroid) 3%pt Lipid disorders - Screen lipids Addisons
Alagille
Autosomal domimant JAG1 genemutation (90%), notch 2 gene mutation
Intrahepatic biliary hypoplasia
Cardiac: Peripheral pulmonary stenosis, TOF
Butterfly vertebrae
Eyes - posterior embryotoxin
Facial: Deep set eyes, pointed chin, wide forehead, prominent nose
Renal abnormalities
Oedema Ddx
Renal - CKD, Nephrotic
Liver - CLD (albumin)
Bowel - PLE (stool A1AT), IBD, CF
Nutritional - protein/calorie malnutrition
Local causes - lymphadenopathy
Drugs - steroids. calcium channel blockers
Non pitting oedema
- Lymphoedemea
- Myxoedema
Macrocephaly short
Dysmorphic
Growth
HC x 3 ; ask for parents HC (average adult 56cm)
Palpate - shunt, fontanelles, sutures Eyes (LR palsy CN6 increased ICP ; upward gaze palsy - Parinaud) Spine - ? spina bifida Skin - neurocutanoeus <2 - developmental, >2 Neuro exam (UL, LL, Cerebellar) bone, abdomen(HSM)
Ddx
- Large bones - achondroplasia, rickets, OI
- Large brain
- SOTOS,
- Neurocutaneous: NF1, TS, SWS ;
- Metabolic (MPS)
- Cerebral tumours - Hydrocephalus
- Communicating (impaired CSF absorption) - post meningitis, bleed
- Non communicating / obstructive: aqueduct stenosis, posterior fossa tumours
- Dandy walker malformation - cystic enlargement of 4th ventricle and posterior fossa
Microcephaly Ddx
Congenital (Pre-natal)
- Brain malformation - lissencephaly
- Syndrome/chromosomal
- Cornelia de lange, angelmans, T21, Fanconi - Hereditary
- Metabolic
Acquired (Post natal)
- TORCH
- FASD
- Endo - hypothyroid, hypo pit
- malnutrition
- HIE, meningitis
Exam
- inspection
- HC, other growth ; check if Hx preterm
- check hearing and vision
Friedreichs ataxia
AR disorder FXN gene on Ch 9, triplet repeat GAA
Age 5-15 onset Absent knee jerk but upgoing plantars Pes cavus Ataxia, Rombergs positive Loss vibration/proprioception, distal sensory loss Cerebellar dysarthria
Optic atrophy
Hyperglycemia, risk T1DM
Cardiac - HOCM
Charcot Marie tooth
CMT 1A - demyelinating
CMT2 - axonal
CMT1a - PMP22 gene duplication
Distal calf atrophy (champagne bottle leg),
pes cavus, hammer toes
Loss reflexes
Spina bifida long
NTD (issue first trimester; failure closure D17-28)
Pregnancy Hx: RF NTD - AEDs, nutritional, genetic
Folic acid supplementation, prenatal diagnosis
If mum has child spina bifida, 3x risk in future pregnancy
Diagnosis and early management Childs function / ADLs and self help skills Bowel care Bladder care Education -? cog impair
Comp
CNS
1. Hydrocephalus - ? shunt
- 90% Arnold chiari 2 (displacement of cerebellar tonsils and vermis through Forman magnum, caudal displacement of medulla and spinal cord, risk compression of brainstem causing cerebellar dysf, CN palsy, hydrocephalus
- Symptoms - swallowing issues, aspiration, dysarthria, OSA, stridor/abnormal cry, spasticity UL
- Issues with shunt
2. Syringomyelia - cavity of central canal spinal cord, assoc with scoliosis, lower limb weakness and deformities.
3. Scoliosis - congenital / acquired due to syrinx / shunt dysfunction / tethered cord. 50% MMC have scoliosis
4. Tethered cord- requires surgical intervention in 1/3, usually during growth spurts such as adolescence
- Gait changes, lower limb pain, change in motor or sensory function, new orthopaedic / foot deformities
Inx MRI, Rx surgery (outrage syrinx/shunt dysfunction)
Cognitive disability - issues maths, attention
- 80% normal IQ but issues maths, executive function
Urinary issues - UTIs, reflux, CKD
Bowel issues
Ortho - feet/hips/spine
6Ss
- spine/skeleton - spine/hip surveillance, talipes (50%) ; if progressive foot deformity Ddx syrinx / tethering
- SDB - seen in 20%, need sleep study if level above t10
- Skin - sensory level, pressure sores, review equipment
- Senses - check vision and hearing
- Size - growth and puberty
- Seizures (15-20% patients)
Issues adolescence
- mood, dependence, self care
- Fertility/relationships
Females with level below L3 have vulval sensation and can have orgasm, normal fertility
Discuss contraception, folate supp if planning pregnancy, risk 1/20 for child spina bifida
Males - 70% get erections, 50% ejac; 20%orgasm ; many infertile males
LATEX allergy - 500x risk due to early exposure
Management points
Motor disability and mobility devices, contractors, skin pressure sores
Bladder management ; worsening bladder control often indication of tethered cord/syrinx/shunt issue
Oxybutinin (antichol) and intermittent catheter
If issues with catheters - ? mitronfanoff ;
? bladder augmentation ; urodynamics once old enough
Rx UTIs, monitor for CKD (regular renal US) - 5-10%pt
CKD mineral bone disease - risk fractures
Bowel issues - Rx constipation, rectal emptying
Consider irrigation system (Peristeen) / MACE
Turners long case
1/2500 females
Total or partial loss X chromosome
45X (50%), others mosaic ; variable phenotype
Birth - lymphedema hands/feet, short and webbed neck
Dysmorphic features: epicanthal folds, abnormal ears,neck webbing, short stature, low posterior hair line, wide spaced nipples, shield chest, hyper convex nails, wide carrying angle, madelung deformity, shortened 4th metacarpal, multiple nevi
Complications
- CVS: elongated transverse aortic arch ; 16% bicuspid AV, risk AS/AR, 11% have coarctation ; risk PAPVR
Risk aortic root dilation - needs monitor, ++risk with pregnancy. Screen with ECHO/MRI every 5yrs
Monitor for HTN
- Vision/hearing: Recurrent OME - combo CHL and SNHL
Risk strabismus, ptosis, cataracts, epicentral folds.
? hearing aids or glasses
-Renal: 1/3 kidney issues - horseshoe kidney , duplex collecting system. Risk recurrent UTIs
Screen with US every 5yrs. Monitor for HTN
- Short stature (SHOX def)
- GIT: Risk coeliac (5%, screen every 2 years), IBD ; increase LFTs 40%
- Hypothyroidism 10-30% (Hashimotos), annual TFTs from age 10
- Puberty (1/3 enter spontaneous puberty), 3% spontaneous periods
>90% have gonadal failure
Pubertal induction at 12-14 ; Pelvic US prior - growth - plot of TS specific chart; Rx with growth hormome
- Dental issues - high palate and dental overcrowding
- Risk obesity and T2DM
- Bone health (improves with GH and oestrogen ) - scoliosis, hips, arthritis
Psychsocial/Education
- ? issues cognition ; maths ; social
- Behavioural issues
- Bullying
- Speech issues
- Fertility discussions
If Y chromosome present - risk gonadoblastoma, prophylactic removal gonads
central cord lesion presentation
LMN signs in the upper extremities and UMN signs in the legs, bladder dysfunction, and loss of sensation caudal to the lesion.
There may be considerable recovery, particularly in the lower extremities.
Charcot Marie tooth (HSMN)
CMT1A most common (demyelinating)
-CMT1a - AD, presents with distal weakness, sensory loss, absent DTR, per caves and hammer toes.
Due to PMP22 duplication
Delayed motor and sensory conduction studies
- CMT2(axonal)
Symptoms/signs
inverse champagne leg appearance due to muscle wasting, foot drop (due to weakness of dorsiflexion)
PES CAVUS and hammer toes
Can involve upper limbs too (less than LL)
May have palpably enlarged nerves (popliteal/tibial)
High stoppage gait
Risk hip dysplasia and scoliosis
Use AFOs
Guillan Barre
Ascending paralysis (AIDP)
Post infectious polyneuropathy
- Symmetric ascending paralysis (LL>UL) ; weak+flaccid
- Loss reflexes
Risk bulbar involvement in 1/2, respiratory compromise
10-15% require ventilatory support
MFS(ataxia, ophthalmoplegia, Areflexia)
Autonomic signs - HR/BP instability, constipation, urinary retention
LP - elevated CSF protein (1/3 N if done first week)
MFS - IgG Ab to Gq1b
MRI brain and spinal cord - thickening of Cauda Equina
Rx IVIG or PLEX
10% go on to need repeat IVIG
7% go on to develop CIDP (>2 relapses >8weeks apart)
Ddx for acute hemiplegia
Stroke
Stroke mimics • Todd’s paralysis • ADEM (Acute Disseminated EncephaloMyelitis) • Mass lesions, eg. Neoplasms • Trauma (NAI) • HSV encephalitis • PRES (Post. Reversible Encephalopathy Syndr.) • Complicated migraine • Metabolic eg.MELAS (Mitochondrial)
Spastic diplegia Ddx
CP: Prematurity - PVL
Dopa responsive dystonia - median onset 6yrs, diurnal variation
Tethered cord / spinal cord ischaemia
Vit E deficiency
Ask about bladder bowel
Any upper limb involvement
Birth Hx, prematurity
Vitamin E deficiency signs
Patients may have cerebellar disease, posterior column dysfunction, and retinal disease.
Loss of deep tendon reflexes is usually the initial finding. Subsequent manifestations include limb ataxia (intention tremor, dysdiadochokinesia), truncal ataxia (wide-based, unsteady gait), dysarthria, ophthalmoplegia (limited upward gaze), nystagmus, decreased proprioception (positive Romberg test), decreased vibratory sensation, and dysarthria.
Friedreichs ataxia
AR disorder of spinocerebellar tracts (dorsal column)
triplet repeat disorder GAA repeat, Frataxin gene
Ataxia (before age 10) LL>UL Upgoing plantars, absent ankle pes cavus, hammer toes, kyphoscoliosis dysarthria speech nystagmus Loss vibration and proprioception, Rombergs+ve
Cardiac: HOCM
Diabetes
Noonan Syndrome
• AD (often inherited) ; 1:1000-1:2500
PTPN11 mutation in 50%
Rasopathy, Noonans gene panel
Triad: Dysmorphic, short, cardiac
• Short stature
• Facial dysmorphism (can be very subtle)
- Hypertelorism, epicanthal folds, ptosis, diamond shaped eyebrows, down slanting palpebral fissures
-Short webbed neck, low posteriorly rotated ears, low posterior hairline, short broad nose, broad forehead, triangular face
• Chest deformities (wide spaced nipples, pectus excavatum), webbed neck, short/squared off fingers
Wide carrying angle
• Cardiac (50-80%) - PS(dysplastic PV) - most common - Superior axis - Hypertrophic cardiomyopathy, 20% Others: VSD, ASD, TOF
- Lymphatic (chylothorax, increased NT)
- Self-limited feeding problem (25%)
- Cryptorchidism (60 – 80%)
- Global developmental delay, language delay
- Learning difficulties, reduction in IQ but intellectual disability not typically severe
- Bleeding diathesis
- Increased risk childhood malignancy e.g. JMML, neuroblastoma
Ddx - CFC, costello, turner, LEOPARD
Monitor: growth, echo, hearing, development
Prader Willi
• 1:10 000 – 30 000
• Infancy – hypotonia, feeding difficulties
• Later infancy/childhood – excessive eating/food seeking behaviour
• Gradual development of obesity
• Developmental delay – motor and language
• Cognitive impairment
• Behavioural phenotype (tantrums, stubbornness, manipulative behaviour, OCD characteristics, self-harm)
• Short stature – GH responsive
• Facial features – narrow bifrontal diameter, almond shaped PFs,
thin upper lip, downturned corners of mouth
• Strabismus 60-70%
• Hypogonadism – incomplete pubertal development, infertility
• GH treatment increases lean body mass, reduces fat mass, increases mobility, improves language and cognitive skills
Angelmans
- 1:12 000 -24 000
- Severe developmental delay (6-12 months) and ID
- Severe speech impairment
- Gait ataxia/tremulousness of limbs
- Behavioural phenotype – inappropriate happy demeanour, frequent laughing/smiling, excitability, hand-flapping
- Microcephaly (postnatal)
- Seizures 80% (generally before 3y), abnormal EEG, with a characteristic pattern of large- amplitude slow-spike waves
- Feeding problems common
- Normal puberty and fertility
Klinefelters
- 47,XXY ; 1:600 males
- 1/3 diagnosed in childhood – language delay, hypotonia/motor delay • Learningdifficulties,IQreducedcomparedtosiblings
- 1/3 diagnosed in adolescence – puberty delay (hypogonadism)
- Long legs, gynecomastia (50%)
- Small, firm testes
- 1/3 diagnosed in adulthood (usually when investigated for infertility) • Increased risk type 2 diabetes, osteoporosis, CVD
- Testosterone replacement • ART (testicular biopsy/ICSI)
Williams Syndrome
Deletion on Ch7 (7q11.2), most de novo, affected individuals have 50% chance of passing on
• Distinctive face
- Broad forehead, bitemporal narrowing, periorbital fullness, stellate/lacy iris pattern, short nose, broad nasal tip, long philtrum, wide mouth
Narrow face and long neck, small widely spaced teeth
• Cardiac abnormalities (elastin arteriopathy)
- Supravalvar aortic stenosis 75%
- Peripheral pulmonary stenosis
• Hypertension
• Anaesthetic risk (high risk for cardiac arrest)
• Connective tissue abnormalities
• Herniae, rectal prolapse, soft lax skin
Bowel/bladder issues
- Hypercalcaemia in infancy
- Hypothyroidism
- Feeding difficulties, FTT and short stature
- Increased risk for type 2 diabetes, obesity in adults
• Variable level intellectual disability ~100%
- visuospatial issues
• Personality - Overfriendliness, empathy, like music
• Psychiatric - Generalized anxiety, specific phobias, attention deficit disorder
Poor sleep
Vision / hearing issues
Dental issues
Neuro: axial hypotonia, peripheral hypertonia
Ataxia short
Exam
Ddx
Inx
Incoordination of movement and balance due to dysfunction
o Cerebellar
o Sensory or motor pathways (connecting to CB)
Aetiology
a) Cerebellar
- Congenital
i) Congenital CNS anomalies - Dandy-Walker syndrome, Chiari malformation, encephalocele, agenesis of CB vermis
ii) Spinocerebellar degenerative - AT, Friedrich ataxia, olivopontocerebellar atrophy, abetalipoproteinemia (also a metabolic disorder)
iii) Other degenerative - GM2 gangliosidosis, neuronal ceroid lipofuscinosis, Pelizaeus-Merbacher disease
iv) Metabolic - arginosuccuric aciduria, maple syrup disease, pyruvate decarboxylase deficiency, Hartnup disease, Vitamin E deficiency - Acquired
i) Infectious
- Acute cerebellar ataxia (post-viral e.g. varicella, coxsackie, echovirus), cerebellar abscess
- Miller Fischer variant of GBS (ataxia, ophthalmoplegia, areflexia)
ii) Toxins
- ETOH, ethylene glycol, sedatives, hypnotics, thallium (used occasionally as pesticides), lead, mercury, hydrocarbon fumes
- Anticonvulsants (CBZ and especially phenytoin, when serum level >30mcg/mL = 120umol/L)
iii) Tumours
- Cerebellar tumours
- Frontal lobe tumours - ataxia by destruction of fibres connecting frontal lobe with CB
- Neuroblastoma – encephalopathy characterised by progressive ataxia, myoclonic jerks, opsoclonus (non-rhythmic horizontal and vertical oscillations of the eyes)
iv) Trauma – head injury
v) Other - vascular events, migraine, seizures
b) Vestibular disease
1. Acute labyrinthitis – middle ear infection, intense vertigo, vomiting and abnormal labyrinthine function (esp ice water caloric testing)
c) Posterior column loss (V & P)
1. Subacute combined degeneration of the cord – B12 def (symptoms similar to Friedrich’s ataxia - UMNL of LL with absent ankle reflexes, dorsal column loss, peripheral sensory neuropathy, also optic atrophy & dementia)
2. Tabes dorsalis
3. Diabetes
4. Hypothyoroidism
d) Peripheral neuropathy (DAM IT BICH)
1. D = Drugs - isoniazid, vincristine, phenytoin, nitrofurantoin, cisplatin, heavy metals, amiodarone
2. A = Alcohol
3. M = Metabolic – diabetes, CRF
4. I = Infective – GBS but usually predominantly motor
5. T = Tumour (leukaemia, lymphoma)
6. B = B12 deficiency
7. I = Idiopathic
8. C = CTD – SLE, PAN
9. H = Hereditary – HSMN
History
1. Onset of ataxia o Acute (*most common) • Infectious* (acute post-infectious, labryinthitis, Miller Fischer variant GBS) • Drug ingestion* • Seizure, head injury, vascular event (stroke), brain tumour, hydrocephalus o Developing chronic • Tumour • Neurodegenerative
- Underlying cause
o CNS abnormality/degenerative – associated congenital anomalies, FHx
o Metabolic – FHx
o Infectious – features of acute infectious, labyrinthitis
o Tumour – Sx of ICP
o Exposure to drugs and toxins
o Recurrent respiratory and sinus infections (ataxia telengiectasia) - Developmental Hx - ? just clumsy or true ataxia
Examination
1. CNS examination o CB function (speech, vision, gait) – abnormality of CB hemispheres o Gait veers towards involved side o Wide based and unsteady gait o Dysmetria of ipsilateral extremity
- Lower limb neuro
o Motor function and reflexes abnormal gait may arise from muscle weakness and spasticity
o Sensory function - Fundoscopy (neurodegenerative)
- Systemic exam - cutaneous stigmata (ataxia telangiectasia)
Investigations
- Bloods
o FBE, UEC
o +/- toxicology screen blood (and urine)
o +/- metabolic screen (amino acids, lactate, pyruvate, ammonia, pH, ketones) - Other
o CT/MRI needed - if no lesion, detailed metabolic and genetic evaluation
o +/- LP (after imaging)
o VMA/HVA urine if think neuroblastoma (need image chest and abdomen as well)
Prader willi syndrome
Long
Methlylation disorder with absence of paternally expressed genes from the chromosome 15q11- q13 region
Diagnosis methylation testing
-70% paternal deletion, 25% maternal UPD, rest methylation defect
Infancy - central hypotonia, poor feeding and FTT
Older
Dysmorphic - almond eyes, thin upper lip, downturned mouth, straight border to side of legs/ulnar border
Issues
Hypothalamic dysfunction
Poor sleep
Hyperphagia and obesity - risk T2DM, OSA
Developmental and cognitive delay
Short stature and GH insufficiency. Small hands/feet
Behavioral problems - skin picking, tantrums, manipulative behaviour, OCD
Neuroendocrine abnormalities.
- GH deficiency
- Hypogonadism
- Central Hypothyroidism
- T2DM
- Central adrenal insufficiency (Risk of adrenal crisis with GH treatment)
Eye problems - strabismus
Monitor bone health, scoliosis - need Ca and Vit D
Behaviour
Nutrition
Endocrine ; GH treatment
Sleep
22q11 deletion syndrome
CATCH 22
Cardiac
- Conotruncal defect - 3XTAPS
TOF ; Interrupted aortic arch, VSD ; tricuspid atresia/truncus arteriosus
Abnormal face
- Hypertelorism, abnormal ears, bulbous nasal tip
- Asymm crying face
Thymic hypoplasia / T cell defect
Cleft palate and pharyngeal insufficiency
HypoPTH and Hypocalcemia
Others - low IQ Feeding issues Renal issues - horseshoe kidney, abnormal structure Seizures High incidence Psychiatric disorders
FISH for 22q11.2
Chorea Ddx and exam
CP Wilsons Neurodegn - Lesch Nyan, Huntingtons Sydenhams chorea Drugs SLE AT
Stick out tongue
Pronator sign (hands above head)
Milk maids grip
Cerebellar short
Inspection, HC (? tumour), ? shunt ; telangiectasia, BP Speech - sizzling sausage Nystagmus Truncal ataxia Gait - ataxia (fall to side of lesion) Rombergs +ve Tremor, hypotonia, past pointing Dysdiadokinesis Pendular reflexes
Look eyes (KF rings, telangiectasia, papilloedema)
Syndromic assoc
FA (pes cavus, hammer toes, absent knee/ankle reflex) ; T2DM, HOCM
Ataxia telangiectasia
Wilsons
Neuroblastoma
Bardet Biedl (RP, Polydactylyl, obese, hypogonad)
MRI
FBC, UE, LFT, metabolic, toxicology
Peripheral Neuropathy causes
DAM IT BICH
Drugs - vincristine, isoniazid Alcohol Metabolic - CRF, DM Infective - GBS Tumour - Leukaemia/lymphoma B12 def Idiopathic CTD - SLE HSM neuropathy - CMT
Hemiplegia EXAM and Ddx
Observation Speech (Dysphasia if dominant hemisphere) Intellect Skin - Neurocutaneous, bruising HC, scars, shunt
Gait examination
- Circumduction gait, arm flexed
FOG test
Sensory neglect (pronator drift)
COMPLETE EXAM
Upper limb
Cranial nerves
Cardiac exam
Determine level - cortex, IC, brainstem, spinal cord
Parietal lobe signs (Cortical)
- Dominant lobe (LIRA - left right confusion, ideomotor apraxia (brush teeth), receptive aphasia, agraphia)
- Non dominant - constructional apraxia (draw clock)
Visual fields (lesion at IC or above)
Cranial nerves, esp CN7 (UMN above pons, LMN pons)
CORTEX: Face and arm>leg, cortical signs
IC: dense hemi, homonymous hemianopia
Brainstem: Ipsi CN palsy, contr hemi
Spinal cord - face spared
Ddx Congenital causes (Antenatal / Perinatal causes) - Hemiplegic CP - Vascular - Structural - Congenital infections
Acquired
- Stroke:
- – Ischaemic - moyoma, CARIAC(thromboembolic): CHD, RHD, SBE, ; sickle cell, thrombophilia ; NF1, homocystinuria
- –Haemorrhagic - coagulopathy, AVM, tumour, haemophilia
- Vasculitis (SLE, takayasu)
- Neoplasm
- Trauma
- Infective (HSV encephalitis, meningitis, abscess)
- Metabolic (MELAS)
- Autoimmune - ADEM
Ddx facial weakness
Bilateral weakness with ptosis +/- ophthalmoplegia
- Moebius (CN 6,7) (facial palsy, CN6palsy, absent pectorals, hypoplastic fingers)
- MG
- MD
B/L weakness with no ptosis
- myopathy
- CP with bilateral UMN facial palsy
- GBS
Unilateral facial nerve palsy
- UMN (forehead sparing): check gait, VF
Causes: Tumour, vascular
- LMN (forehead involved):
Idiopathic / Bells, Ramsay Hunt, check ears for OM, parotid gland
Tacrolimus
SE
Medications that affect levels
HTN, Hyperkalemia, GI upset Neuro: Peripheral neuropathy and Tremor Renal impairment Hyperglycemia Hypomagnesemia
Things that increase Tac level
Antibiotics: Macrolides ; cipro
Omeprazole ; NSAIDs, Fluconazole
Things that decrease Tac levels
AEDS - CBZ, Phenytoin ; Rifampicin
Liver transplant
Graft survival - 90% 1 year, 80%5years
Done when liver decompensated
- Hepatorenal, encephalopathy, refractory ascites
Indications
- impaired synthetic function (albumin low, high INR)
- intractable malnutrition / FTT
- Varices from portal HTN
- poor QOL (intractable pruritius, lethargy, anorexia)
Diseases
- EHBA (biliary atresia) - most common >50% LTx
- Metabolic condition - CF, AAT def, GSD, tyrosinemia
- Acute hepatic necrosis
- Primary biliary cirrhosis / cholestatic liver Dx
- Malignancy
Donor must be ABO matched
Immune suppression
- Tac, MMF, steroids(weaned over 12mo)
Complications
- Acute rejection (most common first 3/12 post transplant, no effect graft function )
- Late rejection - due to SE immune supp - infection/PTLD
Fever, deranged LFTs, jaundice, pain
Rx pulse steroids, increase TAC
- Infections: Bacterial, Viral (EBV/CMV), fungal
- Biliary comp (20%) - cholangitis
- PTLD.- EBV driven, occurs 3-12mo post LTx
Rx by decreasing Tac ; consider rituximab - SE immune supp - renal impair, HTN, T2DM
- Recurrence primary liver disease - autoimmune, hepatoblastoma (monitor AFP)
- Thrombosis of anastomosed vessel (risk highest first 3/12, Rx Anticoag)
NB compliance AVOID LIVE vaccines Need VZIG/IVIG if measles or VZV exposed PCP prophylaxis until 1 year post CMV prophylaxis x 3/12 with valgan
Back to school 3/12 post transplant Good hygiene, no swimming Nutrition Skin surveillance Psychological support - parents and child
Renal Transplant short
Appears, growth ; Vitals - BP
evidence PD / HD
Hands - nails, wrists, pulse, BP
JVP for overload
Eyes - cataracts SE, fundo to check for RP
Hearing aids (Alports)
Medication SE - BP, Hirsutism, weight, gum hypertrophy Heart/lungs Abdo - scars, PD site, transplant - ballot ; bruit - Check liver (ARPKD) lymphadenopathy (PTLD) Rash on legs, peripheral oedema, sensation
Hx Renal transplant - Diagnosis, Inx, complications, treatment Bladder / bowels Growth, BP Bones Skin Fluid intake
Meds EPO for anaemia Immune suppression and SEs Special feed / restrictions ? GH for growth ACE for BP UTI prophylaxis CMV prophylaxis (for 3/12, valgan) Cotrimoxazole (PCP prophylaxis for 6/12 post) IMMS status
Check regular bloods, viral serology
Biopsy at 3/12 and 12/12 - check for CNI toxicity, allograft nephropathy, subclinical rejection
Monitor BP, lipids
Bone bloods, Vit D
US at 1,5,10years post transplant
No live IMMS, may need VZIG/IVIG if exposed
Impact
Complicance
Sick plan
School / mood / finances
Ddx graft dysfunction renal
Infection - UTI, EBV/CMV, BKV Obstruction Medication-tac/ciclosporin Perfusion Dehydration Rejection
Horners syndrome
Ptosis, miosis, anhidrosis
Lesion along sympathetic pathway
Ddx
- Congenital (iris heterochromia)
- Post cardiac surgery
- Neuroblastoma
- Brachial plexus lesion (Klumpkes)
- Mediastinal / apical lung tumour
- MS / stroke / spinal cord lesions
Lateral medullary syndrome (brainstem)
vertigo and ataxia,Horner syndrome.
- abnormal eye movements, ipsilateral limb ataxia, and a dissociated sensory loss (loss of pain and temperature sensation on the ipsilateral face and contralateral trunk)
JDM
Peak 4-6, 12-13
Skin Gottrons papules Heliotrope rash Sun exposed rash Calcinosis
Symmetrical proximal muscle weakness
Elevated CK, LDH, AST
Dilated nail fold capillaries
Cardioresp comp - DCM, conduction abnorm
GI/renal; swallow weak
CNS/ophthal
25-30% full recovery , no relapse
50-60% relapsing course
Small percentage chronic
CMAS to assess severity
SLT
LUNG FUNCTION
Steroids, taper over 2 years
MTX
VACTERL
Vertebral anomalies Anal atresia +/- fistula Cardiac (VSD0 TE - tracheo-esophageal fistula Renal anomalies Limb anomalies (Polydactyly, humeral/radial hypoplasia,)
Fanconi Anaemia
Inherited BM failure syndrome
Short stature Radial ray and thumb abnormalities Skin: CAL HEAD: bird like face, microcephaly, epicanthal folds, low set ears, CHL, strabismus Renal: ectopic/horseshoe/absent kidney Hypospadias / abnormal genitalia Cardiac: PDA, VSD Endo: Hypothyroid, DM Malignancy risk
Diagnosis; Chromosomal breakage analysis
Rx: HSCT
Haemophilia long case
Age diagnosis, presentation ;
TYPE A (factor 8 def) ; B (factor 9 def). BOTH XLR
2/3 family Hx, 1/3 spontaneous mutation
APTT prolonged–> genetics
Complications - joint/brain/skin/airway Treatment and prophylaxis ; analgesia Inhibitors (20-30% with A) - Low responders - higher dose - High responders - may need recomb Factor7 - Immune tolerance, Rituximab Frequency of infusions Activity limitation Acute emergency plan
Prophylaxis Imms Dental care, surgery ? CVAD genetics
Factor replacement in emergency
Joints - RICE
Avoid NSAIDS for pain
Sickle cell long
Age Dx, Symptoms Complications - Crises - acute chest - Stroke - Splenic sequestration - Renal - Eyes: Retinopathy, SE hydroxyurea
Acute Mx plan
Avoid precipitants
Splenic function - ? need extended imms
- Risk infection encapsulated organisms - pneumococcal, salmonella (OM)
Treatment: Hydroxyurea
? HSCT
6/12 review, emergency plan
SE Hydroxurea - BM supp, teratogenic
Adherence, transition
Thalassemia
BETA THAL
Anaemia Extramedullary haematop - frontal bossing Iron overload - Endocrine: growth F, hypothyroid, DM - Cardiomyopathy (annual ECHO) - Liver: cirrhosis and portal HTN (Liver US, LFTS) - Brain Pigement bile stones Hypersplenism (thrombocytopenia) Short stature, pubertal delay
Transfusions chelation timing and SE (cataracts, SNHL, annual eye and hearing review ) IMMS Genetic testing (25% risk recurrence) HSCT
Retts
XLD, mutation MECP2 gene, 99% sporadic
Occurs only females
Normal initial development followed by regression from 6-18months with loss of speech and purposeful hand movements and development of stereotypic hand movements and abnormal dyspraxia gait.
Features Hand stereotypes - wringing, clapping Ataxic/apraxic gait Abnormal respiration - hyper vent and aponea ; bruxism Deceleration of head growth Prolonged QTc Eye pointing Abnormal sleep ASD behaviour, loss speech, poor eye contact Scoliosis Epilepsy and seizures in 80-90% - Rx AEDs, ketogenic diet Autonomic dysfunction Feeding issues - PEG fed, GORD, abdominal bloating, constipation Decreased sensitivity to pain Bone health
4 stages
- Delay ; (6-18mo)
- Regression (1-4yo)
- Unapparent slow deterioration (2-10)
- Motor deterioration - become wheelchair dependent by adults
Kabuki syndrome
AD, KTM2D gene
high arched eyebrows, eversion lateral 1/3 eyebrows, long palpebral fissures Cleft lip/palate ; abnormal ears ID ; short stature Spine abnormalities Cardiac: CoA, VSD Renal/GI issues
