Stems Flashcards
18 month old female - previously normal, now not speaking, hand flapping?
RETT Syndrome 1:8,500 MECP2 Girls Neurological disorder
Apraxia
Lack of meaningful speech
Disordered gait
Abnormal autonomic (sweating)
Abnormal breathing
Sudden cardiac death
NF1 -
Gene locus?
Inheritance pattern?
Gene product and function?
Incidence?
17q11.2
AD
Neurofibromin is tumour suppresor
Incidence is 1:3000
NF1
Diagnositc Criteria
Diagnostic Criteria (2 or more cardinal clincial features)
•≥6 café-au-lait macules (≥1.5cm post-pubertal or ≥0.5cm in prepubertal) •≥2 neurofibromas (any type) or ≥ 1 plexiform neurofibroma
•Freckling – axillary and/or inguinal
•Pilocytic astrocytoma of optic pathway
•≥ 2 Lisch nodules (iris hamartomas) •Dysplasia of sphenoid or long bone cortex
* First degree relative with NF1
TS -
Gene locus?
Inheritance pattern?
Gene product and function?
Incidence?
TSC1 9q (Hamartin) OR TSC2 16p (Tuberin)
mTOR Regulators via RHEB GTPase
AD - 50% Family Hx
Hamartomas and benign neoplastic lesions
Seizures/Mental retardation/behaviour abnormalitis/infantile spasms
1:6000
TS
Diagnostic Criteria
Major:
Definite–Major Features x2 or Major x1 and Minor x2
Probable - Major 1 and Minor 1
Suspect - Major 1 or 2=> Minor
Major: Facial angiofibroma or forehead plaque Non traumatic ungual or periungual fibromas >3 hypomelanotic macules Shagreen Patch Multiple retinal nodular hamartoma Cortical Tuber Subependymal nodule Subependymal giant cell astrocytoma (In 6-14%) Cardiac Rhabdomyoma Lympangiomatosis Renal Angiomyololipoma
TS
Diagnostic Criteria
Minor
Definite–Major Features x2 or Major x1 and Minor x2
Probable - Major 1 and Minor 1
Suspect - Major 1 or 2=> Minor
Minor:
Multiple pits in dental enamel Hamartomatous rectal polyps Bone cysts Central white matter migration lines Gingival fibroams Nonrenal hamartomas Retinal achromic patch “Confetti” skin lesions Multiple renal cysts
Retinoblastoma
Locus?
Function?
Incidence
RB1 13q14
Tumour suppressor
Phosphoprotein that restricts cell cycle from G1 to S
(Therefpre requires biallelic inactivation)
Associated risk of Osteosarcoma, soft tissue sarcoma, breast Ca
Stickler’s syndrome?
“Hereditary progressive arthro-ophthalmodystropy”
Collagen defects in COL2A1, COL11A1, COL11A2
Type 2 and Type XI collagen products
AD
~1:10,000
Retinal Detachment in first decade
Cataracts
Glaucoma
Empty central cavity of eyeball
Depressed nasal bridge
Midfacial hypoplasia
Micrognathia, glossoptosis, cleft palate (Pierre Robin Sequence)
Kyphoscoliosis
Joint hyperflexibility
Peripheral arthropathy
Hearing Loss
CHARGE Syndrome -
Acronym and gene
C – Coloboma of the eye, central nervous system anomalies
H – Heart defects
A – Atresia of the choanae
R – Retardation of growth and/or development
G – Genital and/or urinary defects (hypogonadism, undescended testicles, besides hypospadias)
E – Ear anomalies and/or deafness and abnormally bowl-shaped and concave ears, known as “lop ears”.
CHD7 in 65%, A Chromodomain Helicase involved in chromatin remodelling
“Variable expressivity”
Leading cause of “deafblindness”
VACTERL Association?
V - Vertebral anomalies A - Anorectal malformations C - Cardiovascular anomalies T - Tracheoesophageal fistula E - Esophageal atresia R - Renal (Kidney) and/or radial anomalies L - Limb defects
Genetic Testing - Variant Classification, scale from 1–5?
1-2 Presumed benign
3 Variant uncertain clinical significance
4-5 Presumed pathogenic
- Absent from controls
Affects evolutionarily conserved regions
Variants leading to sever protein changes if loss of function inthat gene know nto be pathogenic
+/- Segregates with disease in multiple inviduals/functional data
What is the role of the paediatrician in global developmental delay?
As PART OF A MULTIDISCIPLINARY TEAM Recognise presence of developmental delay Establish or rule out ‘medical’ causes Limit unnecessary investigations Establish a formulation Hear parents concerns Advocate for services/supports/accomodations Provide a trajectory/long term follow up
What is the “pick up” rate for various investigations in global developmental delay?
Karyotype Molecular 12-20%
Fragile X - 2-5% pick up
MRI 13 % if no features up to 25% if features (big head/focal seizures/abnormal neurology)
Metabolic Ix 1% unless targeted
Investigations in global developmental delay?
Saliva for Molecular Karyotype (Microarray) and Fragile X
Bloods for cK, Thyroid, Iron studies
Neuroimaging - MRI - balance risk of GA
Other stuff targeted:
Lead, B12, Vitamin D, Urine organic, Plasma amino acids
EEG often abnormal 5% but aetiologically yields diagnosis rarely
Serotinergic Syndrome
Agitation Autonomic Instability (Tachycardia) Diaphoresis, Hyp?tension Clonus - inducible, sustained Myoclonus Brisk hyperreflexia Hypertonicity in lower limbs Fluctating
