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Coffin-Siris Syndrome (CSS) is a genetic syndrome associated with multiple congenital anomalies due to mutations in the BAF-complex or SOX gene. Although well characterized overall, the subunits of the BAF-complex or SOX gene affected demonstrate phenotypic differences which are continuing to be defined. Among the variants is the SMARCE1 mutation, the least common identified genotype. This case report presents a pediatric patient with SMARCE1-related CSS, the seventh case reported in the literature. The congenital anomalies are discussed and compared to the reported cases of SMARCE1-related CSS and CSS overall with an emphasis on otolaryngologic manifestations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cleft lip (CL) with or without cleft palate (CL[P]) has a complex etiology but is thought to be due to either genetic or environmentally induced disruptions of developmental processes affecting the shape and size of the facial prominences (medial nasal, lateral nasal, and maxilla). Recent advances in landmark-based morphometrics enable a rigorous reanalysis of phenotypic shape variation associated with facial clefting. Here we use geometric morphometric (GM) tools to characterize embryonic shape variation in the midface and head of six strains of mice that are both cleft-liable (A, A/WySn, CL/Fr) and normal (BALB/cBy, C57BL, CD1). Data were comprised of two-dimensional landmarks taken from frontal and lateral photographs of embryos spanning the time period in which the facial prominences fuse (GD10-12). Results indicate that A/- strain mice, and particularly A/WySn, have overall smaller midfaces compared to other strains. The A/WySn strain also has significant differences in facial shape related to retarded development. Overall, CL/Fr strain mice are normal-sized, but tend to have undersized maxillary prominences that do not project anteriorly and have a small nasal contact area. These results suggest that the etiology of clefting differs in A/WySn and CL/Fr strains, with the former strain suffering disruptions to developmental processes affecting overall size (e.g., neural crest migration deficiencies and lower mitotic activity), while the latter strain has defects restricted to the shape and size of the maxilla. A combination of molecular experimentation and phenotypic analysis of shape is required to test these hypotheses further., (c 2006 Wiley-Liss, Inc.)

For over 40 years, all children with orofacial clefts in Slovenia have been treated at the Department of Maxillofacial Surgery in Ljubljana, which maintains a register of these anomalies. Since 1987, clefts have also been registered within the framework of the perinatal Information System. An analysis of patients included in each of the two sources showed that an estimated 3.5% of cases were missing from the Cleft Register of the Department of Maxillofacial Surgery and 15% from the Perinatal Registry. The incidence of clefts in the period 1973-1993 was 1.64 per 1000 live births, with an increasing trend of 0.02 per year. Considerable differences were established among different geographic regions of Slovenia. Comparison with the data for Finland, Denmark, Hungary, Poland and Bohemia revealed some synchronicity of fluctuations in the incidence of clefting in these countries. The last two observations suggest that exogenous factors of two types play a part in the aetiology of orofacial clefts: some are limited in their action to a small geographical area, while others exert their influence simultaneously in areas several thousand kilometers apart.

A case of oblique facial cleft with supernumerary deciduous molars, probably caused by amniotic bands is reported. Besides facial cleft, and cleft palate and lip, there are sulci on the left side of the face and on the left posterior alveolar ridge. The sulci may be impressions of amniotic bands at a late gestational age and supernumerary teeth may also be related to these amniotic bands.

The authors performed a serological observation of toxoplasmosis by using the methods of IFT, CFT and ELISA in 118 mothers and their children with orofacial clefts. The results were compared with those gained in the control group of healthy mothers and their children. Titre means of toxoplasma antibodies in inflicted mothers and their children were higher than in the control group. The results were evaluated statistically. The authors assume that a certain proportion of orofacial clefts may be induced by toxoplasmosis. (Tab. 6, Ref. 13.).

Holoprosencephaly malformations, of which the fetal alcohol syndrome appears to be a mild form, can result from medial anterior neural plate deficiencies as demonstrated in an ethanol treated animal model. These malformations are associated with more medial positioning of the nasal placodes and resulting underdevelopment or absence of the medial nasal prominences (MNPs) and their derivatives. Malformations seen in the human retinoic acid syndrome (RAS) can be produced by administration of the drug 13-cis-retinoic acid in animals. Primary effects on neural crest cells account for most of these RAS malformations. Many of the malformations seen in the RAS are similar to those of hemifacial microsomia, suggesting similar neural crest involvement. Excessive cell death, apparently limited to trigeminal ganglion neuroblasts of placodal origin, follows 13-cis retinoic acid administration at the time of ganglion formation and leads to malformations virtually identical to those of the Treacher Collins syndrome (TCS). Secondary effects on neural crest cells in the area of the ganglion appear to be responsible for the TCS malformations. Malformations of the DiGeorge Syndrome are similar to those of the RAS and can be produced in mice by ethanol administration or by "knocking out" a homeobox gene (box 1.5). Human and animal studies indicate that cleft lips of multifactorial etiology may be generically susceptible because of small MNP)s or other MNP developmental alterations, such as those found in A/J mice, that make prominence contact more difficult. Experimental maternal hypoxia in mice indicates that cigarette smoking may increase the incidence of cleft lip by interfering with morphogenetic movements. Other human cleft lips may result from the action of a single major gene coding for TGF-alpha variants. A study with mouse palatal shelves in culture and other information suggest that a fusion problem may be involved.

Reliable information on embryonic and fetal development of the human oro-facial system is meager. Much of the data available at present is not entirely reliable, because it was derived from a small number of specimens. An embryological approach with human materials is important for establishing a normal standard of development including individual variabilities as well as clarifying the embryogenesis and etiology of defective development (Nishimura et al. 1977). It is important in human craniofacial embryology to know the variabilities, that is, individual differences in developmental phenomena of the oro-facial region during human prenatal life. In recent times the importance of morphologic investigations of human development has received less emphasis. Yet, without thorough knowledge of the basic facts of prenatal human development, erroneous assumptions can be made in more dynamic approaches and lead investigators astray. Knowledge of prenatal development of human orofacial structures and some of their deviations will therefore be welcomed by many basic scientists and clinicians in the field of facial clefts and other craniofacial malformations. The author was engaged in the collection and systematic study of human embryos and fetuses with Dr. Hideo Nishimura, Emeritus Professor of Kyoto University, Kyoto, Japan, and has been studying the normal and abnormal development during prenatal life. Several results obtained from the study of a large number of specimens are presented laying stress on the orofacial development.

This article presents the results of prospective evaluation of 428 patients with facial clefts or velopharyngeal insufficiency who were evaluated through the Cleft Palate Program at Children's Hospital, San Diego. Children were examined for patterns of major and minor malformations, and an attempt was made to identify the etiology of the overall pattern of altered structure. Results indicate that 14 percent of 259 patients with cleft lip +/- cleft palate, 55 percent of 139 patients with cleft palate, 75 percent of 24 patients with velopharyngeal insufficiency, and 83 percent of 6 patients with atypical clefts had a multiple malformation syndrome. The frequency with which syndromic clefting occurs is higher than previously recognized. Recognition of underlying etiology is important with respect to prognosis and recurrence risk counseling of families and patients. In addition, the underlying diagnosis may significantly impact outcome of medical and surgical treatment of the cleft disorder.

A wide variety of deformities are seen by the craniofacial team. To facilitate the coding and retrieval of data collected, a system has been devised in which an attempt is made to transfer different clinical problems into units which can be processed more efficiently and encoded more exactly. The different surgical manipulations used form the basis of this system. Careful forethought and understanding are prerequisite for the utilization of this system by the craniofacial team.

The clefting in this case involved the face and alveolar processes. The supernumerary teeth were associated with the clefts and situated mesially of the cleft on the left side and distally on the right.