Neurofibromatosis noonan syndromeQ87.1

Noonan and Ehmcke, 1963; Watson, 1967

Rare syndrome with pulmonary valve stenosis, café-au-lait spots, mental retardation, dwarfism, macrocephaly, Lisch nodules. Common clinical signs of peripheral neurofibromatosis.

Panethnic, at 1/2,500 live births.

Controversial. An association with autosomal-dominantly inherited mutations of the Watson syndrome gene (WSS gene, gene locus: 17q11.2) with consecutive neurofibromin disorder is suspected.

Congenital. Depending on the phenotype, the symptoms often manifest themselves in early childhood or in young adults.

Very heterogeneous expression in different organs.

• Integument: Lisch nodules (see also peripheral neurofibromatosis). Often café-au-lait stains and axillary freckling. Pigmentation of the oral mucosa. Nevi: Mostly disseminated melanocytic nevi, hemangiomas, circumscribed lymphangiomas, lentigines and nevi spili. Pea-sized, skin-coloured to bluish, broad or stalked neurofibromas. Cutis laxa (especially in infancy). Bulging nail beds of the upper or lower extremity. Keratosis follicularis of the face or on the extensor sides of the extremities. Deep hairline.
• Eyes: Eyes set wide apart, often slanted, ptosis, visual defects (including strabismus, myopia).
• Nose: Broad nostrils, which occasionally lead to restrictive breathing problems in infancy.
• Mouth: Upper lip usually clearly thickened, highly arched palate, small jaw (malocclusion), often delayed teething and increased caries tendency.
• Ears: Deep set and dorsally displaced ears, thickened outer edge and helix, earlobes turned upwards, hearing loss due to frequently blocked ears, occasionally sensory-related hearing loss.
• Neck: Short, wide or running down at the sides (children and adults).
• Chest: Funnel chest, nipples wide apart.
• Spine: Often scoliosis.
• Musculature: Hypotension (reduced muscle tone and overstretching of some joints).
• Heart: pulmonary valve stenosis or malformation.

Factor XI is often degraded. Molecular genetic analysis (karyotype).

Clinic, lab.

Lentiginosis profusa, Dystrophia pigmentosa, Naevus spilus, Albright syndrome, Turner syndrome.

No causal therapy possible. Possible surgical treatment of disfiguring and life-threatening symptoms.