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.

Fig. 1

Clinical features of the patient at age of 8 year-old. a Note the short neck, ptosis, hypertelorism, and down-slating palpebral fissures. The patient also presented a swelling in the lower right cheek, which was his chief complain. b In the lateral view, the low-set and posteriorly angulated ear is evident. c Pectus excavatum and widely spaced nipples were observed

Fig. 2

Panoramic radiograph revealed bilateral mandibular multilocular radiolucencies. On the right side occurred cortical expansion and displacement of the teeth, whereas on the left side the lesion was smaller

Fig. 3

Histopathological features of the giant cell lesions. a Lesions were characterized by the presence of multiple multinucleated giant cells embedded in a fibrous stroma rich in blood vessels and proliferating spindle cells (×100). b High power view showing the giant cells with multiple nuclei and abundant cytoplasm (×200)

Fig. 4

Detection of the PTPN11 mutation in the NS patient. Shown here is a portion of the DNA-sequence eletropherogram of the PTPN11 exon 3. Compared to the normal sequence, the affected patient has a heterozygous C to T transition at nucleotide position 218 of PTPN11 gene. This transition converts a threonine to isoleucine substitution at codon 3 (Thr73Ile) of the PTPN11 amino acid sequence