Neurofibromatosis

History Taking

Chief complaint:

• "I have multiple spots on my skin."

• "I have a lump that is growing."

History of presenting complaint:

• Noticed multiple brownish patches on the skin since early childhood, increasing in number and size over time.

• Presence of soft bumps or lumps under the skin, which may be painful or causing other symptoms.

• Experiencing progressive vision loss or other neurological symptoms like weakness or numbness.

• Frequent fractures or bone deformities.

• Learning difficulties or attention deficit problems in school.

System review:

• Neurological: headaches, seizures, cognitive difficulties, or weakness/numbness in limbs.

• Dermatological: multiple "café-au-lait" macules, freckling in the armpit or groin, skin nodules (neurofibromas).

• Ophthalmological: Lisch nodules in the iris, visual field defects, decreased visual acuity.

• Musculoskeletal: bone pain, curvature of the spine (scoliosis), bowing of the lower leg.

Past medical history:

• History of being diagnosed with attention-deficit/hyperactivity disorder (ADHD) or learning difficulties.

• Any history of childhood malignancy.

• Any history of hearing loss or other neurologic complaints like numbness or paresthesia.

Past surgical history:

• History of surgical removal of any skin nodules or neurofibromas.

• History of any corrective surgeries for skeletal abnormalities such as scoliosis.

Drug history:

• Medications for control of symptoms such as analgesics for pain relief from neurofibromas.

• Medications for ADHD or any other learning difficulties.

• Treatment for any associated conditions, such as antiepileptic drugs for seizures.

Family history:

• Any family members diagnosed with neurofibromatosis or having similar symptoms.

• History of similar skin lesions or lumps, vision problems, or learning difficulties in family members.

Personal history:

• Difficulty in school or job due to cognitive problems or physical manifestations of the disease.

• Emotional distress or anxiety related to the condition.

Social history:

• Impact on relationships and social interactions due to visible manifestations of the disease.

• Restrictions or adjustments in physical activities due to pain or skeletal deformities.

Physical Examination

General examination:

• Multiple café-au-lait macules on the skin.

• Presence of axillary or inguinal freckling.

• Multiple, various-sized neurofibromas on the skin.

• Possible skeletal deformities like scoliosis or tibial bowing.

Examination of hands and arms:

• Neurofibromas may be present.

• Bony deformities due to dysplasia or pathological fractures.

Examination of the mouth:

• Presence of neurofibromas or café-au-lait spots in the oral mucosa.

Examination of the neck:

• Neurofibromas may be present.

Cardiovascular examination:

• No specific findings typically associated with neurofibromatosis.

Respiratory examination:

• No specific findings typically associated with neurofibromatosis, unless a neurofibroma is affecting the chest wall or mediastinum leading to respiratory symptoms.

Abdominal examination:

• Palpable masses, which could be plexiform neurofibromas.

• Possible hepato-splenomegaly if associated with malignancy.

Neurological examination:

• Signs of optic pathway glioma: visual acuity loss, visual field defects, relative afferent pupillary defect.

• Motor and sensory deficits, depending on the location and extent of neurofibromas.

• Learning disabilities may be apparent on cognitive assessment.

Additional examinations:

• Fundoscopy may reveal optic disc pallor or swelling in the case of optic pathway gliomas.

• Detailed skin examination for neurofibromas, café-au-lait spots, and axillary freckling.

• Audiometry if there are symptoms suggestive of acoustic neuroma.

Investigations

Laboratory tests:

• Complete Blood Count: to identify any associated anemia or leukocytosis, suggestive of underlying malignancy.

• Liver function tests: to identify any hepatic involvement.

• Renal function tests: to identify any renal involvement.

• Genetic testing: Confirmation of the diagnosis by identifying mutations in the NF1 or NF2 gene.

Imaging studies:

• MRI Brain: To identify optic pathway gliomas or other intracranial tumors.

• CT scan or MRI of the spine: To detect neurofibromas in the spinal canal or skeletal abnormalities.

• CT scan or MRI of the abdomen: To detect neurofibromas or tumors in the abdomen.

• Whole-body MRI: To identify internal neurofibromas or plexiform neurofibromas.

• X-rays of long bones: To detect dysplasia or pathological fractures.

• Audiometry and MRI: In case of hearing loss, to identify vestibular schwannomas (acoustic neuromas).

Invasive tests:

• Biopsy: to confirm the diagnosis of neurofibroma or other tumors if imaging studies are inconclusive or in case of suspected malignant transformation.

Other tests:

• Slit-lamp examination: To identify Lisch nodules in the eyes.

• Neuropsychological testing: To assess for learning disabilities or attention deficit disorder.

• Ophthalmologic examination: To monitor for optic pathway gliomas in children with NF1.

• Blood pressure measurement: To identify hypertension that could be secondary to renal artery stenosis or pheochromocytoma.

Management

General management:

• Regular follow-up: to monitor for progression or complications.

• Genetic counseling: to inform about the genetic nature and risk of transmission to offspring.

• Multidisciplinary approach: involvement of neurologists, oncologists, dermatologists, ophthalmologists, and other specialists as needed.

• Supportive care: psychological support, counseling for coping with cosmetic issues or learning difficulties.

Medical management:

• Pain management: analgesics for pain related to neurofibromas.

• Antiepileptics: if seizures are present.

• ADHD medications: for associated attention deficit hyperactivity disorder.

• Chemotherapy or targeted therapies: for malignant peripheral nerve sheath tumors or other malignancies.

• Beta-blockers or calcium channel blockers: for associated hypertension, especially in cases of pheochromocytoma.

Surgical management:

• Neurofibroma removal: for symptomatic, cosmetically displeasing, or suspected malignant neurofibromas.

• Surgery for optic pathway gliomas: if causing significant visual impairment or not responding to chemotherapy.

• Surgical correction of skeletal deformities: such as scoliosis or tibial bowing.

• Tumor removal: for symptomatic or compressive tumors like acoustic neuromas.

• Malignant tumors: may require wide surgical resection.

Other:

• Physiotherapy: to manage bone or muscle pain and improve mobility.

• Special educational support: for children with learning difficulties.

• Regular eye exams: to monitor for development or progression of optic pathway gliomas.

• Regular blood pressure monitoring: especially in NF1 patients at risk for pheochromocytoma or renal artery stenosis.

Causes of increased blood pressure in neurofibromatosis

• Renal artery stenosis

• Pheochromocytoma

• Coarctation of aorta