Neurofibromatosis noonan syndrome Q87.1

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

Due to the clinical similarities between Watson syndrome and neurofibromatosis, Allanson et al. (1991) performed linkage studies in families with Watson syndrome using probes known to flank the NF1 gene on chromosome 17. Close linkage to Watson syndrome was found (maximum lod = 3.29 at theta = 0.0).

Upadhyaya et al (1989, 1990) carried out a linkage study on a family with Watson syndrome in the third generation. A close linkage with the DNA marker D17S33 was found. This marker is also the closest marker to NF1. Thus, Watson syndrome and NF1 may be allelic, or it is possible that the pulmonary stenosis is the result of an alteration in a neighboring gene. Using probes flanking the NF1 gene on chromosome 17, Allanson et al. (1991) found the closest linkage to probe HHH202. They interpreted this as an indication that either Watson syndrome and NF1 are allelic or that there is a group of related genes responsible for the various features of Watson syndrome.

Regarding the question of whether Watson syndrome is a syndrome with related genes resulting from the deletion of both the NF1 gene and a gene for Noonan syndrome, Sharland et al. (1992) excluded the proximal region of 17q as the site of the gene in a linkage study in 11 families with Noonan syndrome in 2 or 3 generations.

• 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.

Watson (1967) described 15 individuals from 2 generations of 3 families each with pulmonary stenosis (8/15), cafe-au-lait spots (15/15) and low normal or dull intelligence (12/15). There were 8 males and 7 females; male-to-male transmission was noted. There was no evidence of neurofibromas.

Partington et al (1985) described a father (57 years), his daughter (20 years) and his son (18 years), all of whom had pulmonary stenosis, cafe-au-lait spots and intellectual disability. The daughter also had restricted mobility in her knees and ankles and the father had coronary artery ectasia. None of the affected individuals had neurofibromas, Lisch nodules, lentigines or deafness. Partington et al (1985) claimed that Watson syndrome is distinct from both neurofibromatosis I (NF1; 162200) and LEOPARD syndrome (151100). Although it was not apparent from the original description, short stature is a common feature of Watson syndrome.

Allanson et al. (1989) reviewed the two largest reported families, including members of the extended family that had not been previously studied. They expanded the clinical phenotype to include relative macrocephaly and Lisch nodules in most affected individuals and neurofibromas in at least four family members. Allanson et al. (1991) extended their study to a further family. Neurofibromas were found in about one third of those affected.

Sabzi F et al. (2022) presented a rare new variant of the syndrome in an adult patient with severe pulmonary valve stenosis, aneurysm of the left and right pulmonary artery, short stature, mental retardation, coronary artery disease and skin lesions. The patient underwent open heart surgery with pulmonary valve removal and aneurysm treatment of the main pulmonary artery and its right and left branches.

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