Giant Cell Lesions in Noonan Syndrome: Case Report and Review of The Literature

Abstract

Noonan-like/multiple giant cell lesion syndrome (NS/MGCLS) is a rare condition with phenotypic overlap with Noonan syndrome (NS). Once thought to be a specific and separate entity, it is now suggested to be a variant of the NS spectrum. We report a patient with classical cardinal features of NS, including short stature, mild ptosis, hypertelorism, down-slating palpebral fissures, low-set and posteriorly angulated ears, short neck, pectus excavatum, widely spaced nipples and cryptochidism, which were associated with bilateral central giant cell lesions in the mandible and germ-line mutation (C218T, Thr73Ile) in the exon 3 of the PTPN11 gene. The similar clinical and genetic aspects support the observation that NS/MGCLS is a variant of NS and giant cell lesions are an integrant part of this disorder.

Unilateral giant cell lesion of the jaw in Noonan syndrome

“…This benign lesion appears before the age of 30, occurs predominantly in females and is seen twice as much in the mandibular region compared to its maxillary counterpart (12,13). Multiple and multifocal giant cell lesions are more rare and need to raise the suspicion for brown tumors due to hyperparathyroidism with overproduction of parathyroid hormone (6). Multifocal gnathic giant cell lesions also can occur in cherubism, a rare autosomal dominant disorder characterized by radiolucent lesions causing characThe genetic heterogeneity is reflected by the occurrence of mutations in different genes, including PTPN11, SOS1, KRAS, RAF1, BRAF, SHOC2 and MEK1, resulting in hyperactivation of the RAS-MAPK transduction pathway (7).…”

“…Specific oral findings in patients with NS comprise a deeply grooved philtrum, a high arched palate, micrognathia, dental anomalies with associated malocclusion, delayed tooth eruption, bifid uvula, articulation difficulties andalthough rare -cleft palate (Table I) (1,(3)(4)(5). These features however change throughout life and are partly responsible for the phenotypic variability (1,5,6). Since its large phenotypic variability, mild cases are clinically easily overlooked.…”

Craniofacial and cutaneous findings in Noonan, Costello and LEOPARD syndromes

“…Noonan syndrome is associated with increased ERK-activity induced by RAS activation and, therefore, RANKL up-regulation may lead to development of multiple central giant cell lesions (CGCLs) of the jaws and other parts of the body [ 22 , 23 ]. Co-occurrence of the NS phenotype with multiple CGCLs was named Noonan-like/multiple giant cell lesion syndrome (Noonan-like/MGCL) [ 22 , 23 ]. However, it is still unclear whether Noonan-like/MGCL should be regarded as a separate entity or as a part of the NS spectrum [ 22 ].…”

Chronic pain in Noonan Syndrome: A previously unreported but common symptom

“…Multiple giant cell lesions are non‐neoplastic granulomas of multinucleated Langhans giant cells embedded in a fibrous stroma. Osteoclast‐rich jaw lesions are most common, but there may be no jaw involvement [Beneteau et al, ; Bufalino et al, ]. These lesions can cause pain.…”