Herencia de la anquiloglosia: de tal palo, tal astilla / Ankyloglossia inheritance: like father, like son

Se desconocen la patogenia de la anquiloglosia y la expresión mayor o menor del genotipo que la genera, porque puede presentarse con herencias de diversos tipos: ligada al cromosoma X, dominante y, en algún caso, recesiva. Se presentan cuatro familias con anquiloglosia en distintas generaciones, acompañando lactantes con problemas en la lactancia materna. En todos los casos existía un desconocimiento previo de esta situación en los pacientes y familiares. En nuestra consulta, se atendieron a 326 grupos de hermanos con anquiloglosia. En 133 de ellos no se hizo frenectomía a ninguno, en 96 grupos se intervino a uno de los hermanos, en 91 se intervino a los dos hermanos y en seis, a tres hermanos. Se encontró una prevalencia en hermanos del 44,9%. El infradiagnóstico de anquiloglosia está condicionado por el desconocimiento de algunas consecuencias de esta patología: malposición dentaria, alteraciones de la columna vertebral, trastornos en el habla, problemas respiratorios y apneas, entre otros. Se necesitan muestras amplias para estudiar los mecanismos de transmisión y aclarar la patogenia de esta malformación hereditaria, que afecta a más del 10% de la población

The pathogenesis of tongue tie and the major or minor expression of the genotype that causes it are not known because it can occur with inheritances X-linked dominant or, in some cases, recessive. Four families with tongue tie in different generations, accompanying infants with breastfeeding problems are presented. In all cases there was a lack of prior knowledge of this situation in patients and family members. In our medical office, 326 sibling groups were attended. In 133 of them, no frenectomy was performed, in 96 groups one of the brothers underwent surgery, in 91 the two brothers were operated and in 6, three brothers. Prevalence in siblings of 44.9% was found. The underdiagnosis of ankyloglossia is conditioned by the unawareness of some consequences of this pathology: dental malposition, alterations of the spine, speech disorders, respiratory problems and apnea, among others. Large samples are needed to study the transmission mechanisms and clarify the pathogenesis of this inherited malformation, which affects more than 10% of the population

Unmasking familial CPX by WES and identification of novel clinical signs.

Mutations in the T-Box transcription factor gene TBX22 are found in X-linked Cleft Palate with or without Ankyloglossia syndrome (CPX syndrome). In addition to X-linked inheritance, ankyloglossia, present in the majority of CPX patients, is an important diagnostic marker, but it is frequently missed or unreported, as it is a "minor" feature. Other described anomalies include cleft lip, micro and/or hypodontia, and features of CHARGE syndrome. We conducted whole exome sequencing (WES) on 22 individuals from 17 "a priori" non-syndromic cleft lip and/or cleft palate (CL/P) families. We filtered the data for heterozygous pathogenic variants within a set of predefined candidate genes. Two canonical splice-site mutations were found in TBX22. Detailed re-phenotyping of the two probands and their families unravelled orofacial features previously not associated with the CPX phenotypic spectrum: choanal atresia, Pierre-Robin sequence, and overgrowths on the posterior edge of the hard palate, on each side of the palatal midline. This study emphasizes the importance of WES analysis in familial CLP cases, combined with deep (reverse) phenotyping in "a priori" non-syndromic clefts.

Familial autosomal dominant severe ankyloglossia with tooth abnormalities.

Ankyloglossia is a congenital oral anomaly characterized by the presence of a hypertrophic and short lingual frenulum. Mutations in the gene encoding the transcription factor TBX22 have been involved in isolated ankyloglossia and X-linked cleft palate. The knockout of Lgr5 in mice results in ankyloglossia. Here, we report a five-generation family including patients with severe ankyloglossia and missing lower central incisors. Two members of this family also exhibited congenital anorectal malformations. In this report, male-to-male transmission was in favor of an autosomal dominant inheritance, which allowed us to exclude the X-linked TBX22 gene. Linkage analysis using short tandem repeat markers located in the vicinity of LGR5 excluded this gene as a potential candidate. These results indicate genetic heterogeneity for ankyloglossia. Further investigations with additional families are required in order to identify novel candidate genes.