Neurocutaneous disorders

Chapter 5 Neurocutaneous disorders



Anne R. Halbert, MB BS (Hons), FACD




Neurofibromatosis



1. What are the two main forms of neurofibromatosis?
Neurofibromatosis type 1 (NF-1 or von Recklinghausen’s disease) and neurofibromatosis type 2 (NF-2). NF-1 accounts for 90% of all cases of neurofibromatosis and affects approximately 1 in 3500 individuals. NF-2 is a genetically distinct entity with a prevalence of 1 in 25,000. Both conditions have autosomal dominant inheritance with 50% of cases representing new mutations.

2. Outline the diagnostic criteria for NF-1.
The diagnosis can be made if two or more of the following criteria are present:
• Six or more café-au-lait macules >5 mm in greatest diameter in prepubertal children and >15 mm diameter in postpubertal individuals

• Two or more neurofibromas of any type or one plexiform neurofibroma

• Freckling in axillary or inguinal regions

• Two or more Lisch nodules

• Optic glioma

• Distinctive osseous lesion, such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudoarthrosis

• First-degree relative with NF-1

National Institutes of Health Consensus Development Conference: Conference statement: neurofibromatosis, Arch Neurol 45, 575–578, 1988.


3. Where is the gene for NF-1 located? What protein does it encode?
The NF-1 gene is a large gene mapping to chromosome 17q11.2. It encodes a protein called neurofibromin, which has a role in tumor suppression.

4. What is the earliest skin sign of NF-1?
Café-au-lait macules. These sharply defined, light brown patches may be present at birth but more commonly start appearing in the first year of life (Fig. 5-1). They are noted initially by 4 years or less in all affected children and within the first year in 82% of cases.
image

Figure 5-1. Multiple café-au-lait macules >5 mm in diameter.


Huson SM, Compston DAS, Harper PS: A genetic study of von Recklinghausen neurofibromatosis in southeast Wales. II. Guidelines for genetic counselling, J Med Genet 26:712–721, 1989.


Boyd KP, Korf BR, Theos A: Neurofibromatosis type 1, J Am Acad Dermatol 61:1–14, 2009.


5. What is Crowe’s sign? When does it develop?
Crowe’s sign is freckling of the axillae or other body folds. It develops in 90% of NF-1 patients, usually in middle childhood. These lesions are not really freckles, but multiple small café-au-lait macules.

Key Points: Neurocutaneous Disorders



1. Multiple Lisch nodules are pathognomonic of NF-1.

2. Multiple café-au-lait macules are the earliest skin sign of NF-1, occurring in approximately 80% of affected babies by the end of the first year of life.

3. NF-2 most commonly presents with deafness or tinnitus related to underlying vestibular schwannomas.

4. There are two genetic loci for tuberous sclerosis on chromosomes 9 and 16.

5. In virtually all cases of Sturge-Weber syndrome, the facial port wine stain involves some of the V1 distribution.

6. Hypomelanotic macules are a useful diagnostic skin sign for tuberous sclerosis in infants with seizures.

6. When do peripheral neurofibromas appear in NF-1?
Peripheral neurofibromas usually start to develop during puberty but increase in size and number in early adult life. They are soft, pink, or flesh-colored papules, nodules, or tumors distributed mainly over the trunk and limbs (Fig. 5-2). Multiple neurofibromas can develop or existing neurofibromas may enlarge during pregnancy.

7. What is a plexiform neurofibroma?
It is a diffuse, elongated neurofibroma occurring along the course of a nerve, usually the trigeminal or upper cervical nerves. Present in 30% of patients with NF-1, these lesions are mostly congenital. They are often disfiguring, associated with overlying skin hypertrophy, hyperpigmentation, and increased hair (Fig. 5-3).

8. What are Lisch nodules?
Melanocytic hamartomas of the iris. When multiple, these lesions are pathognomonic of NF-1, occurring in more than 90% of patients by the second decade of life. They are best seen on slit lamp examination.

9. What is the most common central nervous system (CNS) tumor occurring in NF-1?
Optic glioma occurs in 15% of patients, usually before 6 years of age. Two percent of affected individuals develop other CNS neoplasms including astrocytomas, schwannomas, and hamartomas. Epilepsy occurs in 6% of patients, often due to these underlying focal lesions.
image

Figure 5-2. Multiple peripheral neurofibromas.


image

Figure 5-3. Soft baglike lesion of a plexiform neurofibroma.


Friedman JM, Birch PH: Type 1 neurofibromatosis: a descriptive analysis of the disorder in 1728 patients, Am J Med Genet 70:138–143, 1997.


10. How common is intellectual impairment in NF-1?
Nearly 50% of patients have mild intellectual impairment or learning difficulties; 5% have moderate to severe retardation.

11. What are the most common skeletal abnormalities in NF-1?
• Macrocephaly: 45%

• Short stature: 34%

• Dysplasia of a long bone, most commonly tibia: 14%

• Kyphoscoliosis: 11.5%

12. How frequently should patients with NF-1 be assessed? What should this assessment include?
An annual assessment is usually sufficient. The clinical examination should include a blood pressure measurement (hypertension occurs in 6% due to renovascular stenosis or pheochromocytoma) and a full neurologic examination. Children also require a regular eye examination; surveillance for kyphoscoliosis, precocious puberty, and hypogonadism; and regular developmental assessments. Investigations should be guided by symptoms or physical signs.

Drappier J-C, Khosrotehrani K, Zeller J, et al: Medical management of neurofibromatosis 1: a cross sectional study of 383 patients, J Am Acad Dermatol 49: 440–444, 2003.

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Vasculitis Lichenoid skin eruptions Acne and acneiform eruptions Disorders of pigmentation Panniculitis Special considerations in skin of color

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Apr 26, 2016 | Posted by in Dermatology | Comments Off on Neurocutaneous disorders

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