AHNH + Vinson Cheng Teaching Flashcards
Management of Paediatric problems
- Explanation of condition
- Education and Counselling
- Multidisciplinary approach
Febrile convulsion (Uptodate)
NOT considered a form of epilepsy (recurrent nonfebrile seizures)
Definition:
- A convulsion associated with an elevated temperature >38oC
- A child >6 months - <5 yo
- Absence of CNS infection / inflammation
- Absence of acute systemic metabolic abnormality that may produce convulsions
- No history of previous afebrile seizures
2 types:
1. Simple febrile seizures (most common)
- Generalised seizure
- <15 mins
- Not recur in 24 hours
- Generalised tonic-clonic seizures mainly (but may also be atonic / tonic)
- Complex febrile seizures
- Episodes that have a focal onset (e.g. shaking limited to one limb / one side of the body)
- >15 mins
- More than once in 24 hours
DDx:
- Epilepsy (Infantile spasm)
- CNS infection
- Non-epileptic events / movements
Felix Lai:
West syndrome: Infantile spasm + Hypsarrhythmia (abnormal interictal high amplitude waves and a background of irregular spikes) + Mental retardation / regression (arrest of psychomotor development)
Vinson Cheng:
Spinal muscular atrophy
Etiology:
- Autosomal recessive
- Genetic mutation in *Chromosome 5q13
—> A telomeric copy SMN1
—> A centromeric copy SMN2 (SMN2 gene is a disease phenotype modifier, more number of SMN2 genes —> more SMN protein produced to compensate for loss of SMN1 gene —> less severe the disease is (SpC Paed))
4 types (some say 5)
(1. SMA0 (Prenatal onset, respiratory support at birth (Felix Lai))
2. SMA1 (Infantile, Werdnig-Hoffman disease, onset <6 months) (唔識坐 (Felix Lai))
3. SMA2 (Intermediate, Dubowitz disease, onset 6-18 months) (most in examination) (識坐唔識行)
4. SMA3 (Juvenile, Kugelberg-Welander disease, onset >18 months) (識行但成日跌)
5. SMA4 (Adult onset)
Investigations (Felix Lai):
1. CK level (should be normal, DMD / BMD: abnormal)
2. Molecular genetic testing (homozygous deletions of exon 7 of SMN1 gene located on chromosome 5)
3. Muscle biopsy +/- Sural nerve biopsy
Management:
1. Breathing
- Ventilation
- PT
- Sputum clearance
- Nutrition (e.g. ***gastrostomy)
- Orthopedics
- PT
- OT
- Orthotic device
- Electric wheelchair
- Assistive technologies - Drugs
- Nusinersen (new drug: antisense nucleotide that modifies the alternative splicing of the SMN2 gene —> more SMN protein produced)
- Gene therapy (Onasemnogene abeparvovec (Zolgensma))
Gait examination
Types of gait:
1. Spastic hemiplegic gait
- Affected upper limbs flexor tone (adducted and internally rotated in shoulder), decreased arm swing, fisting of hands
- Affected lower limbs extensor tone, decreased heel strike +/- circumduction
- Spastic diplegic gait
- Extensor tone of both lower limbs
- Scissoring gait / Crouching gait, Small steps, decreased heel strike - Dystonic / Dyskinetic gait
- Choreoathetosis, Dystonia, Rigidity - Waddling gait / Trendelenburg gait (Myopathic gait)
- Pelvic tilting - Ataxic gait
- Wide based stance, truncal ataxia / unsteadiness - High steppage gait (Neuropathic gait)
- Foot drop, decreased heel strike, increased hip flexion - Antalgic gait
Facial nerve palsy
Congenital:
- Moebius syndrome (Underdevelopment of CN6, CN7)
Acquired:
- Birth injury
Neurocutaneous syndrome
- Neurofibromatosis type 1 (NF1)
- Tuberous sclerosis (TS)
- Sturge-Weber syndrome (SWS)
Tuberous sclerosis (TS)
See SpC Revision Session 23
- Autosomal dominant inheritance
- Prevalence 1:6000 to 1:10000 live births
- Variable phenotypic presentation
- Gene mutation testing available
- TSC1 (9q24, encode harmatin) / TSC2 (16p13.3, encode tuberin) gene mutation in ~85% patients
- Harmatin-tuberin complex downregulates mTOR C1
- Seizures occur in 80% of patients, many present with infantile spasms, though all seizure types can be encountered as they grow older
- Vigabatrin is 1st treatment of choice for infantile spasms associated with TSC
- Diagnosis: Clinical criteria
Diagnosis:
- Definite TSC: 2 major / 1 major + 2 minor / Positive genetic testing
- Probable TSC: 1 major + 1 minor
- Possible TSC: 1 major/ >=2 minor features
Major features:
- Facial angiofibromas or forehead plaque
- Nontraumatic ungual or periungual fibroma
- Hypomelanotic macules (>=3) (Ashleaf spots)
- Shagreen patch (connective tissue nevus)
- Multiple retinal nodular hamartomas
- Cortical tubers
- Subependymal nodule (SEN)
- Subependymal giant cell astrocytoma (SEGA)
- Cardiac rhabdomyoma
- Lymphangioleiomyomatosis (LAM)
- Renal angiomyolipoma
Minor features:
- Nonrenal hamartoma
- Retinal achromic patch
- “Confetti” skin lesions
- Multiple renal cysts
- Multiple, randomly distributed pits in dental enamel
- Hamartomatous rectal polyps
- Bone cysts
- Cerebral white matter radial migration lines
- Gingival fibromas
Evaluation:
1. Skin, Teeth, Eyes: Clinical examination
2. Brain: MRI, EEG, TAND
3. CVS: Echo, ECG
4. Kidney: USG, MRI, Hypertension screen, eGFR
5. Lungs: HRCT, Lung function
6. Genetics: 3 generation family history, Genetic testing
Surveillance:
1. Skin, Eyes: Annual
2. Teeth: Biannual
3. Brain: MRI every 1-3 years until 25, EEG based on clinical need, TAND annually
4. CVS: Echo every 1-3 years until rhabdomyoma regress, ECG every 3-5 years
5. Kidneys: MRI every 1-3 years, Annual BP, eGFR
6. Lungs: HRCT every 5-10 years, Lung function annually
From Vinson Cheng:
- Adenoma Sebaceum (Angiofibromas)
- Periungal Fibromas
- Hypomelanic macules (Ashleaf spots)
- Shagreen patches: Lower back
- Coloboma
- Mental retardation, epilepsy and developmental delay
- TSC1/2 mutation —> too much mTOR activation —> abnormal cell growth/proliferation
- Rare multisystem AD genetic condition
- non-cancerous tumours in brain / other vital organ
From Felix Lai:
- Vogt triad = Facial angiofibroma + Seizure + Intellectual disability (mental retardation)
- Mutation in either TSC1 / TSC2 gene (tumour suppressor genes)
- De novo mutation (80%) / Autosomal dominant (20%)
Clinical features:
1. Dermatological
- Angiofibroma
- Ashleaf spots (Hypopigmented macules / Confetti skin lesions)
- Shagreen patches
- Distinctive brown plaque on forehead
- Ungual fibroma
- CNS manifestation
- Glioneuronal hamartoma (Cortical dysplasia (tuber))
- Subependymal nodules (SEN)
- Subependymal giant cell tumours (SGCT) (aka Subependymal giant cell astrocytoma (SEGA))
- Epilepsy
- TSC-associated neuropsychiatric disorders (TAND) (90%) - CVS
- Cardiac rhabdomyomas - Respiratory
- Lymphangioleiomyomatosis (LAM) - Renal
- Angiomyolipoma
- RCC
- Renal cysts - Ophthalmic
- Retinal hamartoma
- Chorioretinal depigmentation (Retinal achromic patches)
From ERS27:
Clinical features:
ASHLEAF
1. Ashleaf spots (Hypopigmented macules)
2. Shagreen patches (鯊魚皮斑病變)
3. Heart rhabdomyosarcoma
4. Lung hamartoma
5. Epilepsy due to cortical tubers
6. Angiomyolipoma in kidney
7. Facial angiofibroma (acne-like)
Treatment:
Rapamycin (Sirolimus) / Everolimus (2nd gen rapamycin derivative)
—> suppress mTOR pathway
Neurofibromatosis type 1 (NF1)
See SpC Revision Session 23
Pathology:
- Germline mutation in 1 of 2 alleles of tumour suppressor gene NF1 on chromosome 17q11.2
- Autosomal dominant
- Although this heterozygous germline mutation is sufficient to cause NF1, somatic loss of function in the second allele is required for tumour formation.
- Neurofibromin (protein product), is important in regulating Ras, a proto-oncogene that plays a prominent role in cell growth and differentiation and is mutated in many common cancers
- Neurofibromin is expressed in most tissues but at particularly high levels in the nervous system (including Schwann cells along peripheral nerve trunks, glial cells, and neurons), which partially explains the predilection for peripheral nerve sheath tumors and gliomas
Mosaic NF1:
- Mosaic NF1 occurs when there is a somatic mutation later in embryonic development (as opposed to a germline mutation in generalised NF1). Mutations that occur very early in embryonic development can present with a phenotype similar to generalised NF1, whereas mutations in terminally differentiated cells typically manifest with isolated areas of involvement. Clinically, the area of involvement may vary from a narrow strip to one-half of the body; although often unilateral, it sometimes involves both sides
- In individuals with suspected mosaic NF1, genetic testing should be performed on blood as well as on the affected tissue (e.g. melanocytes from a CALM)
Clinical features (SpC Revision + Felix Lai):
1. Cafe au lait spots
2. Axillary Freckling
3. Lisch nodules
4. Neurofibromas and Plexiform Neurofibroma
5. CNS tumours (Gliomas)
- Astrocytoma
- Brainstem glioma
- Optic pathway gliomas (OPG) (affect vision / lead to blindness)
6. Soft tissue sarcomas
- Malignant peripheral nerve sheath tumour (MPNSTs)
- Rhabdomyosarcoma
- GISTs
- Glomus tumours
- Phaeochromocytoma
- Wilms tumour
- Juvenile myelomonocytic leukaemia
- Breast cancer
7. Bone abnormalities
- Long bone dysplasia
- Pseudoarthrosis
- Sphenoid wing dysplasia
- Non-ossifying fibroma within long bones
- Short stature
- Scoliosis
- Osteoporosis
8. Neurological abnormalities
- Cognitive deficits and learning disabilities
- Seizures
- Cerebrovascular abnormalities (Aneurysms, Stenosis, TIA)
- Peripheral neuropathy
- Macrocephaly
9. Hypertension
- Essential
- Renovascular
DDx of cafe au lait spots:
1. NF2
2. Schwannomatosis
3. Legius syndrome
4. McCune-Albright syndrome
5. Noonan syndrome
6. Russell–Silver syndrome
Diagnostic criteria:
Revised 2021 NF1 Diagnostic criteria
>=2 of following:
1. >=6 Cafe au lait spots of >5mm in size (before puberty) / 15mm in size (after puberty)
2. Freckling in axillary / groin (inguinal) regions
3. >=2 Neurofibromas of any type / 1 Plexiform neurofibroma
4. >=2 Lisch nodules (abnormal clumps of pigment on coloured portion of eye / >=2 Choroidal abnormalities
5. Optic pathway glioma
6. Certain abnormalities of bone development in the head (∵ thinning of cortex) (Sphenoid wing dysplasia) / abnormal bowing of bones (Pseudoarthrosis) / anterolateral bowing of tibia (Tibial dysplasia)
7. A parent with confirmed NF1
8. A pathogenic NF1 gene variant
Only Cafe au lait spots, Neurofibroma appear at birth, followed by tibial dysplasia, others develop later
SpC Revision:
Cutaneous NFs:
- Within dermis and epidermis
- Initially sessile, later pedunculated
- Red-blue-violaceous -fleshy and soft
- Not painful
Subcutaneous NFs:
- Deep to the dermis
- Skin moves over
- Discrete spherical or ovoid
- Firm, tender or painful
Plexiform NFs:
- Extensive interdigitating network
- Numerous fingerlike fronds that insinuate extensively into adjacent normal tissues
- Surgical removal impossible
- Superficial or deep
- +/- Overlying hyperpigmentation or hypertrichosis
- Usually present at birth
Treatment principles:
- NO specific medical treatment for neurofibromas exists
1. Genetic counselling
2. Treatment of various tumours
- Depends upon type of tumour, its effect on adjacent tissues and related complications
- Surgical treatment + Pain management of plexiform neurofibromas
3. Neurologic disorders that may require specific management
- Include cognitive deficits, learning disabilities, seizures, and peripheral neuropathy
4. Orthopedic intervention may be needed for long bone dysplasia and scoliosis
New drug:
- Selumetinib (MEK inhibitor (inhibit cell proliferation)) (SpC Paed)
Chest scars
Right thoracotomy:
1. Right Blalock-Taussig shunt
2. Right Pulmonary artery banding
3. Esophageal surgery (TEF repair)
4. Congenital diaphragmatic hernia repair (with scar migrating up)
5. Thoractomy
6. Lobectomy
Left thoracotomy:
1. Left Blalock-Taussig shunt
2. Left Pulmonary artery banding
3. Coarctation of aorta repair
4. PDA ligation
5. Thoracotomy
6. Lobectomy
Mid sternotomy:
1. Complex cardiac surgery
2. Any bypass surgery
3. Valvular surgery
4. Pulmonary artery banding
Other scars:
1. Chest drain scars
2. Pacemaker / ICD scars
3. Mediastinal drain scars
Unilateral vs Bilateral kidney enlargement
Unilateral:
1. Polycystic kidney disease
2. Kidney mass / tumour (Wilm’s tumour / Nephroblastoma)
3. Hydronephrosis
Bilateral:
1. Polycystic kidney disease
2. Kidney mass / tumour (Bilateral) (e.g. WAGR syndrome (Wilms tumour-aniridia syndrome))
3. Hydronephrosis (posterior urethral valve)
Thalassaemia major
Facial features:
1. Pallor/ Jaundice
2. Dark complexion
3. Maxillary hyperplasia
4. Spacing of teeth
5. Frontal bossing
Abdominal examination:
1. Abdominal distension
2. Hepatosplenomegaly
3. Needle marks (injection of deferoxamine)
Genetic imprinting syndrome
An epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner
- Prader-Willi syndrome
- Angelman syndrome
- Beckwith-Wiedemann syndrome
- Russell–Silver syndrome
- Pseudohypoparathyroidism
Down syndrome
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
Approach to Eye examination in paediatrics
- General
- Squint (strabismus)
- Cataract
- Coloboma (hole in iris / cleft eyelid, in CHARGE association)
- Heterochromia
- Lisch nodules (NF1)
- Aniridia (Absence of iris, WAGR syndrome) - Red reflexes and Pupils
- Size
- Reactivity - Extraocular movement
- Fundi
- Optic disc
- Papilledema
- Retinopathy
Aniridia syndrome
Genetic congenital eye and medical syndrome usually detected at birth
3 types of inheritance:
- Sporadic
- Familial
- Recessive
WAGR syndrome:
- Wilms’ tumour (usually occurring before 8 yo)
- Aniridia
- Genitourinary abnormalities / Gonadoblastoma
- Retardation / learning disabilities
