Beckwith‐Wiedemann syndrome (BWS) is a genomic imprinting disorder, characterized by macroglossia, abdominal wall defects, lateralized overgrowth, and predisposition to embryonal tumors. It is caused by the defect of imprinted genes on chromosome 11p15.5, regulated by imprinting control (IC) domains, IC1, and IC2. Rarely, CDKN1C and chromosomal changes can be detected. The aim of this study is to retrospectively evaluate 55 patients with BWS using the new diagnostic criteria developed by the BWS consensus, and to investigate (epi)genetic changes and follow‐up findings in classic and atypical phenotypes. Loss of methylation in IC2 region (IC2‐LoM), 11p15.5 paternal uniparental disomy (pUPD11), and methylation gain in IC1 region (IC1‐GoM) are detected in 31, eight, and five patients, respectively. Eleven patients have had no molecular defects. Thirty‐five patients are classified as classical and 20 as atypical phenotype. Patients with classical phenotype are more frequent in the IC2‐LoM (25/31), while patients with atypical phenotype are common in the pUPD11 group (5/8). Malignant tumors have developed in six patients (10.9%); three of these patients have IC1‐GoM, two pUPD11, one IC2‐LoM genotype, and four an atypical phenotype. We observed that the face was round in the infantile period and elongated as the child grew‐up, developing prognathism and becoming asymmetrical if hemi‐macroglossia was present in the classical phenotype. These findings were mild in the atypical phenotype. These results support the importance of using the new diagnostic criteria to facilitate the diagnosis of patients with atypical phenotype who have higher tumors risk. This study also provides important information about facial gestalt.

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Objective To investigate the variant spectrum and genotype–phenotype correlations in a Turkish cohort with Neurofibromatosis Type‐1 (NF1). Materials and methods  We retrospectively investigated the clinical and molecular data of 138 NF1 patients from 129 families who had been followed‐up for a median of 3.9 (1.25–18.5) years. Results NF1 sequencing revealed 73 different intragenic variants, 19 of which were novel. Seven large deletions were detected by multiplex ligation‐dependent probe amplification (MLPA) analyses. The total detection rate of pathogenic NF1 variants was found to be 87.1%. Comparing age groups, cutaneous neurofibromas, freckling, and Lisch nodules were more prevalent in patients older than 12 years (p > .05). Optic glioma detected in 17.3% of the patients and was significantly more common before the age of 6 (p > .001). Other solid tumors developed in 5% of the patients. There was no genotype–phenotype correlation between patients with truncating and nontruncating variants. However, six out of seven patients with large deletions had significant developmental delay, one patient with the c.2970_2972delAAT (p.Met992del) variant had only typical pigmentary features, and another patient with the c.4267A > G (p.Lys1423Glu) variant had CALMs, freckling, neurofibromas, and Noonan‐like phenotype. Conclusions We described 19 novel variants and seven large deletions in NF1. Applying MLPA assay in NF1 is useful in expanding the molecular diagnosis. Although very limited genotype–phenotype correlation has been reported in NF1, the fact that specific phenotypic findings were observed in our patients with large deletions and two intragenic variants supports the studies published recently.

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