Mild nasal clefting may be predictive for ALX4 heterozygotes.
Heterozygous loss-of-function mutations in ALX4 are responsible for enlarged parietal foramina, whereas patients with biallelic ALX4 mutations display a phenotypic spectrum of clinical findings, from mild to severe alopecia, cranium bifidum, hypertelorism, microphthalmia, with alar clefting being the pivotal sign in all affecteds. We report on four affected individuals in a three-generation family, displaying a phenotypic spectrum ranging from mild nasal clefting and broad columella to subtle changes in nasal configuration in addition to parietal foramina, caused by a novel ALX4 mutation (c.646C>G, p.Arg216Gly). This is the second report of a family showing vertical transmission of a dominant ALX4 mutation with facial involvement in addition to parietal foramina, mimicking mild recessive ALX4 phenotype. We discuss possible pathological mechanisms that may have lead to phenotypic variation in the family and challenges in genetic counseling.
Medical Genetics Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Umut
U
Altunoglu
Bilge
B
Satkın
Zehra Oya
ZO
Uyguner
Hülya
H
Kayserili
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000328:Adult; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009666:Nose / Q000002:abnormalities*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000235:genetics*
C416676:ALX4 protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors
ALX4 gene; broad columella; nasal clefting; parietal foramina