Nevoid Basal Cell Carcinoma Syndrome in infants: improving diagnosis.

BACKGROUND: Diagnosis of Nevoid Basal Cell Carcinoma Syndrome (NBCCS) in infants may pose significant challenges to clinicians owing to its variable expressivity and age-related manifestations. METHODS: We report two paediatric cases of NBCCS who presented initially with a non-specific phenotype. RESULTS: In case 1, a diagnosis of NBCCS was possible only after the father was interviewed and found to present with two major criteria for the disease. Subsequent molecular testing confirmed the diagnosis. In case 2, molecular testing of the infant and his father had diagnostic value as neither satisfied fully the current diagnostic criteria for NBCCS. CONCLUSIONS: Presence of the few clinical manifestations of NBCCS that appear in infants, typically congenital malformations and skeletal abnormalities, should prompt clinicians to conduct in-person interviews with both parents. In general, paediatricians should refer both parents of infants who are suspected of having an inherited condition to clinical geneticists for expert examination, given the potential unreliability of reported medical history.

Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth.

Sotos syndrome is characterized by pre- and post-natal overgrowth, typical craniofacial features, advanced bone age, and developmental delay. Some degree of phenotypic overlap exists with other overgrowth syndromes, in particular with Weaver syndrome. Sotos syndrome is caused by haploinsufficiency of the NSD1 (nuclear receptor SET domain containing gene 1) gene. Microdeletions involving the gene are the major cause of the syndrome in Japanese patients, whereas intragenic mutations are more frequent in non-Japanese patients. NSD1 aberrations have also been described in some patients diagnosed as Weaver syndrome. Some authors have suggested a certain degree of genotype-phenotype correlation, with a milder degree of overgrowth, a more severe mental retardation, and a higher frequency of congenital anomalies in microdeleted patients. Data on larger series are needed to confirm this suggestion. We report here on microdeletion and mutation analysis of NSD1 in 59 patients with congenital overgrowth. Fourteen novel mutations, two previously described and one microdeletion were identified. All patients with a NSD1 mutation had been clinically classified as "classical Sotos," although their phenotype analysis demonstrated that some major criteria, such as overgrowth and macrocephaly, could be absent. All patients with confirmed mutations shared the typical Sotos facial gestalt. A high frequency of congenital heart defects was present in patients with intragenic mutations, supporting the relevance of the NSD1 gene in the pathogenesis of this particular defect.