ALX1 has been repeatedly described in association with autosomal recessive frontonasal dysplasia 3. Frontonasal dysplasia 3 presents as a severe form of frontonasal dysplasia characterized by hypertelorism, bilateral extreme microphthalmia, upper eyelid coloboma, sparse eyelashes, absence of eyebrows, wide nasal base, hypoplasia of the ala nasi, bilateral non-midline cleft lip with a prominent glabella, complete cleft palate, and low-set posteriorly angulated ears. At least 2 splice site and 1 missense mutation have been reported in at least 3 probands from 3 publications (PMIDs:20451171,27324866,32914578) Variants in this gene have been also seen to segregation in two families (PMIDs:27324866, 32914578,) This gene disease association is also supported by animal models (PMIDs:8673125, 23059813). In summary ALX1 is definitively associated with autosomal recessive Frontonasal dysplasia 3. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations Gene Curation Expert Panel on 10/13/2022. (SOP Version 9)
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