👤 Giulia Pascolini

The Fibroblast Growth Factor Receptor 1 ( The malformation phenotype of HRTFDS has been reviewed in 26 previously reported patients in terms of single congenital defects, mutational spectrum, impacted protein domains and inheritance. Molecular basis, clinical management, main differential diagnoses and genetic counseling were also illustrated. SHFM was identified in every patient. The other main associated features included craniofacial defects, skeletal malformation identified at radiography, genitourinary anomalies, HPE and cardiovascular disorders. This study extensively recapitulates the malformation phenotype associated with HRTFDS and the underlying molecular perturbations. A multidisciplinary clinical approach is fundamental, in which genetic counseling can have an important role. However, our results are partial and refer to a restricted number of patients, pointing out the necessity of other descriptions and similar research. Additional studies will expand clinical and molecular knowledge as well as further clarify the biological mechanisms. Show less

Koolen-de Vries syndrome (KdVS, MIM#610443) is a rare malformation condition mainly characterized by cognitive impairment in association with craniofacial and visceral anomalies. The core phenotype is caused by mutations in the chromatin remodeler KANSL1 (MSL1V1, KIAA1267, KAT8 Regulatory NSL Complex Subunit 1, MIM#612452), which maps to 17q21.31 critical genomic region (Koolen et al., Nature Genetics 2012;44:639-641). Considering its molecular basis, KdVS is included in the group of Developmental Disorders of Chromatin Remodeling (DDCRs), also termed chromatinopathies. We describe the first KdVS patient of Southern India ethnicity, harboring the typical de novo 17q21.31 microdeletion, including KANSL1. Observed facial features and congenital anomalies are in line with the already reported KdVS phenotype, suggesting that phenotypic features are consistent across different ethnicities. Show less