Disease relevance of Cleft Palate

• The data suggest that first-trimester exposure to diazepam does not materially affect the risk of cleft lip with or without cleft palate or of cleft palate alone [1].
• The hypothesis that in utero exposure to diazepam increases the risk of oral-cleft anomalies was evaluated in a case-control study, in which 445 infants with cleft lip with or without cleft palate and 166 with cleft palate without cleft lip (cleft palate alone) were compared with 2498 control infants having other birth defects [1].
• These data definitively implicate perturbation of TGFbeta signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events [2].
• Differential effects of FGFR2 mutations on syndactyly and cleft palate in Apert syndrome [3].
• These animals die perinatally and exhibit varying combinations of gross developmental defects throughout the second half of development, including acrania, exencephaly, cleft palate, limb abnormalities and omphalocele [4].

Psychiatry related information on Cleft Palate

• This report describes the speech and language development of four children with VCFS studied longitudinally from 6 to 30 months of age and compares their performance with three groups of children: (1) normally developing children, (2) children with cleft lip and palate, and (3) children with isolated cleft palate [5].
• We determined the critical period for cleft palate formation in the presence of all-trans-retinoic acid (RA) and defined anomalous patterns within the variants of palatal rugae [6].
• The relation between maternal restraint and food deprivation, plasma corticosterone, and induction of cleft palate in the offspring of mice [7].

High impact information on Cleft Palate

• The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia [8].
• Non-syndromic cleft lip with or without cleft palate (CL/P, MIM 119530) is among the most common of major birth defects [9].
• Newborn Egfr-/- mice have facial mediolateral defects including narrow, elongated snouts, underdeveloped lower jaw and a high incidence of cleft palate [10].
• Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction [11].
• Deficiency of the beta 3 subunit of the type A gamma-aminobutyric acid receptor causes cleft palate in mice [12].

Chemical compound and disease context of Cleft Palate

• Genes in mice that affect susceptibility to cortisone-induced cleft palate are closely linked to Ir genes on chromosomes 2 and 17 [13].
• We compare results obtained using phenytoin (which induces cleft lip) and 6-aminonicotinamide (which induces cleft palate) [14].
• Cleft lip with or without cleft palate: associations with transforming growth factor alpha and retinoic acid receptor loci [15].
• Two male siblings, born to consanguineous parents, presented with CH, athyreosis and cleft palate and were found to be homozygous for a mutation corresponding to a serine to asparagine substitution at codon 57 (S57N) in the forkhead DNA binding domain of TTF-2 [16].
• Sc5d (-/-) pups were stillborn, had elevated lathosterol and decreased cholesterol levels, had craniofacial defects including cleft palate and micrognathia, and limb patterning defects [17].

Biological context of Cleft Palate

• Cytogenetic evidence, in the form of deletions and balanced translocations, points to the existence of a locus on 2q32-q33, for which haploinsufficiency results in isolated cleft palate (CPO) [18].
• Associated with the rescue of the cleft palate was a restoration of Shh and Bmp2 expression, as well as a return of cell proliferation to the normal levels [19].
• Distinguishing characteristics include cleft lip with or without cleft palate, isolated cleft palate, bilateral lip pits, hypodontia, normal intelligence, and an autosomal-dominant mode of transmission with a high degree of penetrance [20].
• Mutations in the MSX1 homeobox gene are associated with non-syndromic cleft palate and tooth agenesis in humans [19].
• We performed molecular deletion analysis of two further patients with partial monosomy 10p, who showed hypoparathyroidism, deafness, and renal dysplasia or renal insufficiency, but no cardiac defect, cleft palate, or reduced T cell levels [21].

Anatomical context of Cleft Palate

• Moreover, Tbx1-/- mice displayed a wide range of developmental anomalies encompassing almost all of the common DGS/VCFS features, including hypoplasia of the thymus and parathyroid glands, cardiac outflow tract abnormalities, abnormal facial structures, abnormal vertebrae and cleft palate [22].
• They lack whiskers and lower incisors and have defects in their secondary palates, including cleft palate, demonstrating that activin-beta A must have a role during craniofacial development [23].
• Less frequent findings include lacrimal-duct atresia, nail dysplasia, hypohydrosis, hypodontia, and cleft palate with or without bifid uvula [24].
• The opposite trends for severity of syndactyly and cleft palate in relation to the two mutations may relate to the varying patterns of temporal and tissue-specific expression of different fibroblast growth factors, the ligands for FGFR2 [3].
• Mice heterozygous for a null mutation in Tbx1 have mild anomalies, whereas homozygous Tbx1 mutants die at birth with severe defects in the derivatives of the pharyngeal apparatus, including cleft palate, thymus gland aplasia and cardiac outflow tract malformations [25].

Gene context of Cleft Palate

• Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate [26].
• This interval, closely linked and distal to p, and bracketed by the genes encoding the alpha 5 and beta 3 subunits of the type A gamma-aminobutyric acid receptor (Gabra5 and Gabrb3, respectively), contains a gene(s) (cp1; cleft palate 1) necessary for normal palate development [27].
• The Sox9(+/-) mice died perinatally with cleft palate, as well as hypoplasia and bending of many skeletal structures derived from cartilage precursors [28].
• Identification of SATB2 as the cleft palate gene on 2q32-q33 [18].
• Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis [19].

Analytical, diagnostic and therapeutic context of Cleft Palate

• Most beta3-deficient mice die as neonates; some neonatal mortality, but not all, is accompanied by cleft palate. beta3-deficient mice that survive are runted until weaning but achieve normal body size by adulthood, although with reduced life span [29].
• In these and previous studies on cortisone- and other glucocorticoid-induced cleft palate in the mouse, the nature of the cleft-palate-response curve appeared to be the same for all glucocorticoids, and within-strain differences in tolerance could be used as measures of potency or bioassays for a particular effect of the glucocorticoids [30].
• Adrenalectomy of A/J or CD-1 dams resulted in a reduction of endogenous corticosterone, but did not reduce the spontaneous incidence of cleft palate in the offspring [31].
• Diphenylhydantoin (DPH) shares two features with cortisol: immunosuppression and cleft palate formation [32].
• Fryns syndrome is a lethal autosomal recessive multiple congenital anomaly syndrome characteristic "coarse" facies, cleft palate, diaphragmatic hernia, and distal digital hypoplasia [33].

References