Expanding the SPECC1L mutation phenotypic spectrum to include Teebi hypertelorism syndrome

Abstract

Teebi hypertelorism syndrome is a rare autosomal dominant disorder that has eluded a molecular etiology since first described in 1987. Here we report on two unrelated families with a Teebi hypertelorism-like syndrome and Teebi hypertelorism phenotype who have missense mutations in Sperm Antigen With Calponin Homology And Coiled-Coil Domains (SPECC1L), previously associated with oblique facial clefting and Opitz G/BBB syndrome. The first patient and his affected mother were previously-reported by Hoffman et al. in this journal as a new syndrome resembling Teebi hypertelorism and Aarskog syndromes in 2007. This patient had hypertelorism, sagittal and coronal craniosynostosis, ptosis, natal teeth, unusual umbilicus, shawl scrotum, small hands, and feet, with grossly normal development. Our second patient had classic Teebi hypertelorism syndrome with hypertelorism and a giant umbilical hernia. Patient one and his affected mother had a c.1260G>C:p.E420D variant and patient two had a de novo c.1198_1203delATACAC:p.I400_H401del variant in SPECC1L. We review the phenotypic findings in the previously-published Teebi hypertelorism syndrome patients, and the Opitz G/BBB patients with SPECC1L mutations. In addition we emphasize the findings of aortic root dilation and craniosynostosis in these patients, which should be considered in their management.

ALX1-related Frontonasal Dysplasia Results From Defective Neural Crest Cell Development and Migration

“…The true prevalence of FND and the majority of its causes remain unknown. To date, six genetic causes of subtypes of FND with varying patterns of inheritance have been described in individual case reports: EFNB1 (MIM 300035) in X-linked craniofrontonasal syndrome (MIM 304110); ALX3 (MIM 606014) in FND type 1 (MIM 136760); ALX4 (MIM 605420) in FND type 2 (MIM 613451); ALX1 (MIM 601527) in FND type 3 (MIM 613456); ZSWIM6 (MIM 615951) in dominant acromelic frontonasal dysostosis (MIM 603671); and SPECC1L (MIM 614140) in Teebi syndrome (MIM 145420) (Bhoj, Li et al, 2015, Kayserili, Uz et al, 2009, Smith, Hing et al, 2014, Twigg, Kan et al, 2004, Twigg, Versnel et al, 2009, Ullah, Kalsoom et al, 2016, Uz et al, 2010, Wieland, Jakubiczka et al, 2004. The heterogeneity of clinical phenotypes, including a wide range of possible ocular and craniofacial components, likely corresponds to different underlying genetic variants, genetic environments, and epigenetic modifications.…”

Re

“…Patent ductus arteriosus has also been reported by Tsai et al 6 Intra-abdominal abnormalities are common in patients with THTS. For instance, giant umbilical hernia may be present as recently reported by Bhoj et al 7 Hydronephrosis may be seen in some patients. Shawl scrotum is often seen in affected men.…”

SMARCE1, a rare cause of Coffin–Siris Syndrome: Clinical description of three additional cases

“…Exome sequencing (ES) was performed on exon targets isolated by capture using the Agilent SureSelect Human All Exon version 5 kit (Agilent Technologies, Santa Clara, CA) following standard procedures described elsewhere [Bhoj et al, 2015; Miyake et al, 2015]. The prepared sample was sequenced on HiSeq2500 according to the manufacturer’s recommendations (Illumina, San Diego, CA).…”