NF1 long case Flashcards
(23 cards)
What mode of inheritance is NF1?
Autosomal dominant
what gene? what chromosome?
NF1 gene in the long arm of chromosome 17 at 17q11.2
What does the gene code for?
neurofibromin
Neurofibromin 1 is found throughout the nervous system, functioning as a tumour suppressor. Loss of neurofibromin 1 (by somatic mutation) leads to increased risk of development of tumours, both benign and malignant. Hence a loss of neurofibromin occurs in NF1-associated tumours, but many features are not accounted for by the interaction between neurofibromin and ras. The cells most affected by NF1 mutations are derived from the neural crest.
What age do plexiform neurofibromas affecting the head and neck occur?
before the age of 1
50% get these
What age do neurofibromas affecting other parts of the body occur?
before adolescence
When would you expect optic gliomas (OPG) to appear?
From birth until 8 years, optic gliomas can appear
(loss of visual acuity, abnormal colour vision, visual field cuts, strabismus, proptosis or even hypothalamic dysfunction)
When would you expect hypertension to be evident?
from 2 years onwards
When would you expec CAL macules?
3-5 years: axillae and groin freckling; from 5 years onward development of neurofibromas. Lisch nodules are expected between 5-10 years.
(CAL best seen with woods lamp)
When would you expect bony anomalies?
long bone bowing (tibial pseudoarthrosis) and sphenoid wing dysplasia are congenital and are usually noted within the first 2 years; rapidly progressing dysplastic scoliosis typically occurs between 6 and 10.
(Pulsatile proptosis can occur in patients with SWD which causes a bony defect behind the eyeball, and allows the temporal lobe to herniate into the orbit, causing the visible (brain) pulsatility)
When would you expect malignant nerve sheath tumours?
from adolescence onwards
Diagnostic criteria for NF1?
two or more of: 1. six or more café-au-lait macules > 5 mm greatest diameter in prepubertal children, and > 15 mm diameter in postpubertal people; 2. two or more neurofibromas of any type, or one plexiform neuroma; 3. freckling in the axillary or inguinal region; 4. optic glioma; 5. two or more Lisch nodules (iris hamartomas); 6. distinctive osseous lesions such as sphenoid dysplasia or tibial pseudoarthrosis; and 7. a first-degree relative with the NF1.
learning and behavioural issues?
50%-75% have some memory or specific learning disabilities. ADHD symptomatology, low self esteem and poor interpretation of social cues. sleeping difficulties, and headaches.
Scoliosis in NF1?
- Dystrophic scoliosis - rapidly progressing , under the age of 10, shorter segments and a more acute angle.
- Idiopathic scoliosis, rarely needs treatment.
bone health in NF1
reduced bone mineral density, increased bone resporption and vitamin D deficiency, increased risk of fractures.
ddx for HTN in NF1?
- coarctation of aorta
- renal artery stenosis
- neuroendocrine tumours: pheo/neuroblastoma/ganglioneuroma
Cardiac lesions
Pulmonary valve stenosis is the heart defect seen most commonly
Head circumference
above average and height below average.
Tumours LMNOP + DR G
Leukaemia (JCML)
Meningioma/Malignant peripheral nerve sheath tumours
Neurofibromas/Neuroblastoma
Optic Pathway Glioma
Pheochromocytoma
+
Duodenal Carcenoid
Rhabdomyosarcoma
Gliomas
Gastrointestinal fx
Gastrointestinal Stromal Tumours
what is the NF1-Noonan phenotype
Pulm stenosis/webbing/low set ears/hypertelorism/downslanting palpebral fissures/
due to the RAS overlap
Watson syndrome?
NF1 without the neurofibromas
past hx in long case
Initial dx (what age and how)
time period of being informed of dx and development of sx?
what invx?
evolution of sx?
number of hospitalisations and indications?
Development of complicatiins and thier management
Previous medications tried (stimulants/antihypertensives/laser tx/ surgical procedures)
imms/allergies
three generation family hx
what is the surveillance?
Annually
1. development and school progress
2. growth and pubertal development
3. BP
4. auscultation for pulm sten
5. visual ax
6. ax spine and skin
