chapter  14
62 Pages

Neurocutaneous syndromes

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic diseases involving the skin. The estimated prevalence is 1:500 to 1:3000.

Age of onset

● Lesions of NF1 (as well as those of tuberous sclerosis) have specific age of onset: at birth for cafeau-lait spots, during childhood for freckling, and in late childhood and puberty for neurofibromas and plexiform tumors

Clinical findings

● Café-au-lait spots: light-brown macules present at birth and slowly growing with age, distributed randomly with sharp borders and round-oval shape (Figures 14.1-14.4)

● Freckling: small lentiginous-like lesions distributed preferentially on large folds (Figures 14.4 and 14.5)

● Neurofibromas: nodules ranging from 2-3 mm to 1-2 cm in dimension, flesh colored, subcutaneous and slightly protruding, randomly distributed or focused along the course of peripheral nerves (Figures 14.6-14.8)

● Plexiform tumors: large subcutaneous soft tumors (Figures 14.9 and 14.10), with a particular ‘full bag’ texture, located elsewhere on the skin and potentially reaching huge dimensions, becoming the so-called ‘tumeurs royales’ (Figures 14.11-14.13)

Figure 14.1 ● Less frequently hypopigmented ovalar spots similar to those occurring in tuberous

sclerosis are noted, as well as angiomatous-like lesions (Figures 14.14 and 14.15) ● Rarely, alopecic lesions are visible on the vertex (Figure 14.16) ● Mucosal lesions are very rare ● Darker colored skin compared with healthy family subjects ● A soft skin touch, similar to that occurring in Ehlers-Danlos subjects, is detectable in

over 70% of patients ● Itching ● A higher incidence of juvenile xanthogranulomas (Figure 14.17) ● Segmental presentation for both café-au-lait spots and neurofibromas is possible

(Figure 25.28)

Figure 14.3 ● Cutaneous lesions vary widely from subject to subject and even among members of the

same family

Extracutaneous, symptoms ● Lisch nodules, small multiple papules on iris, pathognomonic of NF1

Figure 14.4 ● Macrocephaly with hypertelorism (Figure 14.18) ● Fibrous dysplasia of the sphenoid, highly characteristic of the disease and usually

monolateral ● Scoliosis, lordosis (Figure 14.19) and pseudoarthrosis of joints and dysplastic lesions of

the bones ● Optic nerve and chiasmal gliomas, peculiar to NF1 ● Rarely, other tumors of the nervous tissue may be detected, such as malignant

peripheral nerve sheath tumors but, in general, malignant transformation of tumors is rare

● Early-onset hypertension ● Pulmonary stenosis (this association is known as Watson syndrome) ● Classic mental retardation is overemphasized but rarely present and frequently

confused with the typical poor performance at school of these patients ● Low attention, dyslexia, scarce propensity to scholar discipline may be severe during

the first years of maternal or elementary school, but this gap may be solved during late childhood and pre-puberty

● Soft tissue tumors (retroperitoneal or pelvic) ● Rarely, leukemias in patients with xanthogranulomas

Finally, we experienced in our consultations four subtypes of clinical presentation that may reflect a specific genetic pattern:

● Classic NF1 with café-au-lait spots, neurofibromas and plexiform tumors, with associated CNS symptoms (40% of patients)

Figure 14.7 ● Café-au-lait spots alone, without any other cutaneous or extracutaneous sign (Figure

14.19) (40%) ● Almost ‘complete’ or generalized lentiginosis with intermingled café-au-lait spots with

‘buttonhole’ (soft-tumors, easily compressible lesions) (5%) (Figure 14.20) ● Generalized neurofibromas, usually of small dimension (100-200 lesions), with

plexiform tumors, ‘tumeurs royales’ and usually very few or absent café-au-lait spots with CNS-associated symptoms (15%) (Figure 14.7)

Course and prognosis

The course of the disease is strictly dependent on the extracutaneous involvement.