Nablus mask‐like facial syndrome: Deletion of chromosome 8q22.1 is necessary but not sufficient to cause the phenotype

Abstract

Nablus mask-like facial syndrome (NMLFS) has many distinctive phenotypic features, particularly tight glistening skin with reduced facial expression, blepharophimosis, telecanthus, bulky nasal tip, abnormal external ear architecture, upswept frontal hairline, and sparse eyebrows. Over the last few years, several individuals with NMLFS have been reported to have a microdeletion of 8q21.3q22.1, demonstrated by microarray analysis. The minimal overlapping region is 93.98-96.22 Mb (hg19). Here we present clinical and microarray data from five singletons and two mother-child pairs who have heterozygous deletions significantly overlapping the region associated with NMLFS. Notably, while one mother and child were said to have mild tightening of facial skin, none of these individuals exhibited reduced facial expression or the classical facial phenotype of NMLFS. These findings indicate that deletion of the 8q21.3q22.1 region is necessary but not sufficient for development of the NMLFS. We discuss possible genetic mechanisms underlying the complex pattern of inheritance for this condition.

Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome

“…This reasoning is supported by the description of at least two individuals with large 8q22.1 deletions encompassing PTDSS1 that do not have features of LMS 23 . We therefore performed enzymatic studies in skin fibroblasts from subjects 1, 4 and 5 who harbored p.Pro269Ser, p.Gln353Arg and p.Leu265Pro alterations, respectively.…”

Nablus syndrome: Easy to diagnose yet difficult to solve

“…In 2009, Raas‐Rothschild and colleagues were able to confirm the presence of a deletion of 3.37 Mb at chromosome position 8q22.1 in Teebi's original patient (Raas‐Rothschild et al, ; Teebi, ). Microarray analysis from reported individuals with Nablus syndrome, including the two mother–son pairs, demonstrate an overlapping and contiguous gene deletion at chromosome 8q22.1 in all affected individuals (see Table and Figure ; Allanson et al, ; Barber et al, ; Jamuar et al, ; Overhoff et al, ; Raas‐Rothschild et al, ; Shieh et al, ).…”

“…The classical facial phenotype of Nablus syndrome, seen in a boy at 4 and 15 years of age and his mother (Allanson, , ; Allanson et al, ). Note the frontal upswept hair, telecanthus (boy), bulbous nose, pinna anomaly, cleft lip repair (boy), micrognathia (boy), and sparse lateral eyebrows (mother).…”

“…Note the frontal upswept hair, telecanthus (boy), bulbous nose, pinna anomaly, cleft lip repair (boy), micrognathia (boy), and sparse lateral eyebrows (mother). Figure reproduced with permission (Allanson et al, )…”

“…The diagnosis of Nablus syndrome is made on the basis of the characteristic facial features and is strongly supported by demonstration of a deletion involving 8q21.3‐8q22.1. However, given that this deletion is also present in individuals without Nablus syndrome, it is clear that the presence of this deletion is necessary but not sufficient to cause this condition (Allanson et al, ).…”