Nablus Mask-Like Facial Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome at chromosome 8q22.1.

Description

Nablus mask-like facial syndrome (NMLFS) is a rare entity defined by distinctive facial features, including blepharophimosis, tight-appearing glistening facial skin, an abnormal hair pattern with an upswept frontal hairline, sparse arched eyebrows, flat and broad nose, long philtrum, distinctive ears, and a happy demeanor (summary by Jain et al., 2010).

Clinical Features

Salpietro et al. (2003) described a 21-month-old girl with a striking facial appearance and other characteristics virtually identical to those in a patient reported by Teebi (2000) under the designation Nablus mask-like facial syndrome. Features in both cases, well demonstrated by the photograph of Salpietro et al. (2003), included upswept frontal hairline, tight glistening facial skin, high-arched and sparse eyebrows, absent/scant eyelashes, hypertelorism, blepharophimosis, bulbous nasal tip, prominent smooth philtrum, maxillary hypoplasia with bilateral longitudinal cheek dimples, everted lower lip, small chin, and abnormal ear configuration. The patient of Salpietro et al. (2003) was Sicilian; that of Teebi (2000) was a 4-year-old Palestinian boy. In both cases parental consanguinity seemed likely.

Teebi (2001) discussed the differences between Nablus mask-like facial syndrome and blepharonasofacial syndrome (110050).

Shieh et al. (2006) reported a 17-month-old Asian boy with Nablus mask-like facial syndrome, born of unrelated parents. In addition to the characteristic facial features described by Teebi (2000), the child had camptodactyly, contractures, unusual dentition, cryptorchidism, developmental delay, and happy demeanor.

Raas-Rothschild et al. (2009) reexamined the boy with NMLFS originally described by Teebi (2000), now 10 years of age. His psychomotor development was normal, and his cryptorchidism had been surgically repaired. His height was at the 5th centile with a head circumference at the 2nd centile, and his ear length was 3rd centile with an abnormal shape and unfolded helix; he also had blepharophimosis, telecanthus, flat broad nasal bridge, bluish- and tight-appearing skin around the nose, upsweep of frontal hair, and bilateral Spigelian hernias of the abdominal wall. He had an unaffected twin sister and healthy, nonconsanguineous parents. Raas-Rothschild et al. (2009) also reported the fourth case of NMLFS, a 9-month-old boy with a head circumference at the 3rd centile, broad neck, blepharophimosis, telecanthus, and broad flat nose with bluish, tight skin around the nose. He also had an upswept frontal hairline, contractures of large joints, 'sandal gap' between the first and second toes, and cryptorchidism with a small testicular scrotum. Noting that both sets of parents described their affected child as 'happy,' Raas-Rothschild et al. (2009) suggested that a happy disposition is a behavioral trait typical of NMFLS.

Cytogenetics

Using array-based comparative genomic hybridization (CGH) in a 17-month-old Asian boy with Nablus mask-like facial syndrome (NMLFS), Shieh et al. (2006) identified an approximately 4-Mb deletion involving chromosome 8q21.3-q22.1. Analysis of a 5-year-old girl with NMLFS, originally reported by Salpietro et al. (2003), revealed a similar deletion. Studies of the parents showed that the deletion was de novo in both cases. The results suggested that Nablus mask-like facial syndrome results from a chromosomal microdeletion of 8q. Shieh et al. (2006) noted the phenotypic similarities to those reported by Simosa et al. (1989) in a mother and son with Simosa craniofacial syndrome (182150).

In a mother and son with prominent forehead, deep-set eyes, blepharophimosis, arched eyebrows, small mouth, bulbous nasal tip, low-set dysplastic ears, and partial 2/3 toe syndactyly, Barber et al. (2008) identified a 3.14-Mb deletion at 8q22.1 in addition to a duplication of the distal short arm of chromosome 8. The 22-month-old infant had a head circumference below the 25th centile; his mother was born with cleft palate and had undergone surgery to bring her jaw forward. A male half-sib had died at 7 weeks of age of cytomegalovirus; postmortem report detailed similar facial features to the proband and his mother, as well as cleft soft palate, persistent ductus arteriosus, bowel malrotation, and inguinal hernia.

In a 10-year-old boy with NMLFS who was the original patient described by Teebi (2000), Raas-Rothschild et al. (2009) identified a 3.37-Mb deletion on chromosome 8q22.1, from 92.99 Mb to 96.36 Mb. In a 9-month-old boy with NMLFS, Raas-Rothschild et al. (2009) identified a 7.27-Mb deletion on 8q21.3-q22.1, from 89.07 Mb to 96.34 Mb. The deletions were confirmed by FISH analysis, and were found to be de novo in both cases.

In a 6-year-old boy with only slight elongation of the palpebral fissures and minimally thickened ear helices, who had a normal hair pattern, no joint contractures, and normal genitalia, Jain et al. (2010) identified a de novo 1.6-Mb deletion at 8q22.1, from 94.8 Mb to 96.4 Mb. In contrast to previously described patients, the boy had delayed speech and social development, and psychological assessment indicated he met criteria for an autistic spectrum disorder. Noting that this deletion only partially overlapped those of other reports, Jain et al. (2010) suggested that the nonoverlapping region found in NMLFS cases may represent the critical region for the phenotype.