RESUMO
Cleft lip with or without cleft palate (CL/P) is a complex trait with evidence that the clinical spectrum includes both microform and subepithelial lip defects. We identified missense and nonsense mutations in the BMP4 gene in 1 of 30 cases of microform clefts, 2 of 87 cases with subepithelial defects in the orbicularis oris muscle (OOM), 5 of 968 cases of overt CL/P, and 0 of 529 controls. These results provide confirmation that microforms and subepithelial OOM defects are part of the spectrum of CL/P and should be considered during clinical evaluation of families with clefts. Furthermore, we suggest a role for BMP4 in wound healing.
Assuntos
Proteína Morfogenética Óssea 4/genética , Fenda Labial/genética , Fissura Palatina/genética , Sequência de Aminoácidos , Proteína Morfogenética Óssea 4/fisiologia , Criança , Pré-Escolar , Códon sem Sentido , Humanos , Dados de Sequência Molecular , Mutação de Sentido IncorretoRESUMO
Emerging research suggests that subepithelial defects of the upper lip musculature are part of the phenotypic spectrum of cleft lip and/or palate (CL/P) and may represent an occult, subclinical manifestation of the anomaly. The present study investigates whether similar occult lip defects are present in individuals affected with isolated cleft palate (CP). To this end, upper lip ultrasounds of 33 CP cases (12 males, 21 females) were evaluated retrospectively for the presence of discontinuities (i.e., breaks) within the orbicularis oris muscle (OOM). In four CP cases (2 males, 2 females), distinct discontinuities of the OOM were identified. Of the remaining CP individuals, 23 demonstrated normal lip morphology on ultrasound (7 males, 16 females), while, in 6 cases (3 males, 3 females), a definitive evaluation was not possible. As CP and CL/P are traditionally thought to be etiologically distinct, these findings raise the possibility that some CP cases may be misclassified. Such diagnostic errors could have important implications for recurrence risk estimation and studies aimed at discovering etiology. (c) 2008 Wiley-Liss, Inc.
Assuntos
Fenda Labial/complicações , Fenda Labial/diagnóstico por imagem , Fissura Palatina/complicações , Fissura Palatina/diagnóstico por imagem , Músculos Faciais/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/genética , Fenda Labial/genética , Fissura Palatina/genética , Músculos Faciais/diagnóstico por imagem , Feminino , Humanos , Masculino , Linhagem , Estudos Retrospectivos , Ultrassonografia , Gravação em VídeoRESUMO
The Pittsburgh Oral-Facial Cleft study was begun in 1993 with the primary goal of identifying genes involved in nonsyndromic orofacial clefts in a variety of populations worldwide. Based on the results from a number of pilot studies and preliminary genetic analyses, a new research focus was added to the Pittsburgh Oral-Facial Cleft study in 1999: to elucidate the role that associated phenotypic features play in the familial transmission patterns of orofacial clefts in order to expand the definition of the nonsyndromic cleft phenotype. The purpose of this paper is to provide a comprehensive review of phenotypic features associated with nonsyndromic orofacial clefts. These features include fluctuating and directional asymmetry, non-right-handedness, dermatoglyphic patterns, craniofacial morphology, orbicularis oris muscle defects, dental anomalies, structural brain and vertebral anomalies, minor physical anomalies, and velopharyngeal incompetence.
