Nablus mask‐like facial syndrome is caused by a microdeletion of 8q detected by array‐based comparative genomic hybridization

Abstract

In 2000, Teebi reported on a 4-year-old boy with a distinctive pattern of malformation, which he termed the "Nablus mask-like facial syndrome" (OMIM# 608156). Characterization of this syndrome has been difficult because of the paucity of patients described in the medical literature and its unknown etiology and pathogenesis. We present two patients with Nablus mask-like facial syndrome who both display a microdeletion in the 8q21-8q22 region detected by array-based comparative genomic hybridization. Patient 1, a boy, has a distinct facial appearance characterized by severe blepharophimosis, tight-appearing glistening facial skin, sparse and unruly hair, a flat and broad nose, and distinctive ears that are triangular in shape with prominent antihelices. He also demonstrates camptodactyly, contractures, unusual dentition, cryptorchidism, mild developmental delay, and a happy demeanor. Patient 2, a girl with a strikingly similar phenotype, was previously described in a report by Salpietro et al. 2003. She has distinctive ears, dental anomalies, and developmental delay. The etiology of her pattern of malformation was not identified at that time. Although high-resolution chromosome and subtelomeric FISH analyses were normal, array-based comparative genomic hybridization revealed an approximately 4 Mb deletion involving the 8q21.3-8q22.1 region in both patients. This region encompasses a number of genes that may contribute to this unique phenotype. These results demonstrate a chromosomal microdeletion as the etiology of Nablus mask-like facial syndrome and emphasize the diagnostic utility of array-based comparative genomic hybridization in the evaluation of multiple malformation syndromes of previously unrecognized causation.

The BMP Ligand Gdf6 Prevents Differentiation of Coronal Suture Mesenchyme in Early Cranial Development

“…GDF6 mutations in humans have been associated with eye and postcranial skeletal abnormalities although these effects are characterized by incomplete penetrance and phenotypic heterogeneity [15], [32]. Interestingly, genomic lesions close to the GDF6 genomic region are associated with Nablus Mask-Like Facial Syndrome [33], [34], [35] which is a complex multigene deletion syndrome characterized by loss of a critical region just proximal to GDF6 . In one of only two known patients where the genomic deletion included GDF6 , coronal craniosynostosis was observed [33], [34].…”

The discovery of microdeletion syndromes in the post-genomic era: review of the methodology and characterization of a new 1q41q42 microdeletion syndrome

“…Since the advent of array CGH as a routine research and diagnostic tool in the past several years, numerous new syndromes have been identified, 28 -31,33,34,48,64 and the molecular basis for some known syndromes has been uncovered. [65][66][67][68] The discovery of novel deletions in multiple individuals allows for delineation of critical regions in which to search for genes causing the features of the syndrome. In some cases, true contiguous gene syndromes are identified (e.g., Potocki-Shaffer syndrome, 20,21 LGS 69 ), whereas in others, a single gene results in the complex phenotype (e.g., Alagille syndrome 70 ).…”

Array-based comparative genomic hybridization: clinical contexts for targeted and whole-genome designs

“…25,27 Another example of a cytogenetic anomaly discovered with whole-genome array CGH is the deletion responsible for Nablus masklike facial syndrome (OMIM #608156), a multiple malformation syndrome. 28 Several more novel disorders will be discovered in the near future as whole-genome array CGH is more widely applied.…”