Frontonasal dysplasia (FND) is a heterogeneous group of disorders characterized by hypertelorism, broad nasal tip and root, bifid nose and oral, palatal and facial clefting. Additional findings include microphthalmia, coloboma, and low-set, posteriorly rotated ears. FND1, FND2, FND3 and SIX2 related FND are caused by mutations in the ALX3, ALX4, ALX1 and SIX2 genes. Patients with FND2 can also have skull defects, coronal craniosynostosis, cryptorchidism, agenesis of corpus callosum, total alopecia and mental retardation. Mutations in ALX4 also cause parietal foramina 2, a disorder characterized by symmetrical, oval parietal bone defects, cranium bifidum and scalp defect. Parietal foramina also occurs as part of the Potocki-Shaffer syndrome (PSS; MIM 601224), a rare contiguous gene deletion syndrome due to haploinsufficiency of the 11p12-p11.2 region, encompassing the ALX4 gene.
Craniofrontonasal syndrome (CFNS; MIM 304110) shares clinical features with FND such as hypertelorism, broad nasal tip root, bifid nose, cleft lip and cleft palate. Other prominent features include longitudinal splitting of nails, clinodactyly, abnormal facial proportions, craniosynostosis, low implant of breasts, narrow shoulders, and frizzy and curly hair. CFNS is an X-linked dominant disorder caused by loss-of-function mutations is EFNB1. Paradoxically, CFNS displays greater severity in heterozygous females than in hemizygous males, who typically only have hypertelorism or no clear features at all. Because heterozygous females are uniquely mosaic due to random X-inactivation, individual cells either produce or do not produce functional ephrin-B1protein. This random pattern of expression and non-expression causes abnormal sorting of cells. The cells of the hemizygous males are not able to produce a functional protein and thus the phenomenon cannot occur. A possible explanation for a few severely affected males can be mosaicism.

The frontonasal dysplasia and craniofrontonasal syndrome NGS panel consists of five genes: ALX3, ALX4, ALX1, EFNB1.

Copy number variation (CNV) analysis of the frontonasal dysplasia and craniofrontonasal syndrome panel genes is also offered as a panel. Additionally, CTGT offers a comprehensive test (both NGS and CNV panels) for these genes. Panel genes are also offered as individual sequencing and deletion/duplication tests, unless otherwise indicated.