Hereditary syndrome of ectrodactyly, congenital heart defect and cleft lip and palate

A case of a family of he proband suffering from ektrodaktyly, together with heart defect, cleft lip and palate is reported. The parents came to the genetic counselling center to get the genetic prognosis for a next child. All together 3 cases demonstrating different types of radial defects were registered in this pedigree. The authors discuss possible causes of clinical polymorphism and accent the complications of giving genetic prognosis in such cases.     

Binderoid complete cleft lip/palate

A small subset of infants with complete cleft lip/palate look different because they have nasolabiomaxillary hypoplasia and orbital hypotelorism. The authors' purpose was to define the clinical and radiographic features of these patients and to comment on operative management, classification, and terminology. The authors reviewed 695 patients with all forms of incomplete and complete cleft lip/palate and identified 15 patients with nasolabiomaxillary hypoplasia and orbital hypotelorism. All 15 patients had complete labial clefting (5 percent of 320 patients with complete cleft lip/palate), equally divided between bilateral and unilateral forms. The female-to-male ratio was 2:1. Of the seven infants with unilateral complete cleft lip/palate, one had an intact secondary palate and all had a hypoplastic septum, small alar cartilages, narrow basilar columella, underdeveloped contralateral philtral ridge, ill-defined Cupid's bow, thin vermilion-mucosa on both sides of the cleft, and a diminutive premaxilla. Of the eight infants with bilateral complete cleft lip, one had an intact secondary palate. The features were the same as in patients with unilateral cleft, but with a more severely hypoplastic nasal tip, conical columella, tiny prolabium, underdeveloped lateral labial elements, and small/mobile premaxilla. Central midfacial hypoplasia and hypotelorism did not change during childhood and adolescence. Intermedial canthal measurements remained 1.5 SD below normal age-matched controls. Skeletal analysis (mean age, 10 years; range, 4 months to 19 years) documented maxillary retrusion (mean sagittal maxillomandibular discrepancy, 13.7 mm; range, 3 to 17 mm), absent anterior nasal spine, and a class III relationship. The mean sella nasion A point (S-N-A) angle of 74 degrees (range, 65 to 79 degrees) and sella nasion B point (S-N-B) angle of 81 degrees (range, 71 to 90 degrees) were significantly different from age-matched norms ( = 0.0007 and = 0.004, respectively). The ipsilateral central and lateral incisors were absent in all children with unilateral cleft, whereas a single-toothed premaxilla was typically found in the bilateral patients. Several modifications were necessary during primary nasolabial repair because of the diminutive bony and soft-tissue elements. All adolescent patients had Le Fort I maxillary advancement and construction of an adult nasal framework with costochondral or cranial graft. Other often-used procedures were bony augmentation of the anterior maxilla; cartilage grafts to the nasal tip and columella; and dermal grafting to the median tubercle, philtral ridge, and basal columella. Infants with complete unilateral or bilateral cleft lip/palate in association with nasolabiomaxillary hypoplasia and orbital hypotelorism do not belong on the holoprosencephalic spectrum because they have normal head circumference, stature, and intelligence, nor should they be referred to as having Binder anomaly. The authors propose the term cleft lip/palate for these children. Early recognition of this entity is important for counseling parents and because alterations in standard operative methods and orthodontic protocols are necessary.     

Genetics of cleft lip and cleft palate in China.

During the past 10 years, 60 cases of cleft lip with or without cleft palate [CL(P)] were recorded among 45,072 newborns at Shanghai International Peace Maternity and Infant Hospital, China. The incidence was 1.33 per 1,000 births. The family histories of 163 CL(P) patients were analyzed. The incidences of CL(P) in the first-, second-, and third-degree relatives of CL(P) patients were 11/246 (4.47%), 10/1,032 (0.97%), and 6/1,727 (0.35%), respectively. Of the 163 probands, three had a history of consanguinity of the parents (1.8%), in contrast to 0.77% in the general population. These data are suggestive of multifactorial inheritance. The heritability of CL(P) in our study calculated by Falconer's formula was 77.6%.     

Variation of morphophysiological and genetic demographic traits in children with congenital cleft lip and palate

Medical records and questionnaire data have been used to analyze morphophysiological (the birth weight and length) and genetic demographic (maternal age and marriage structure) traits in a sample of children with orofacial malformations (OMs, cleft palate and/or cleft lip) living in Krasnodar Territory, Russia. The sample of children with malformations (including premature infants) differs from the control group in lower birth weight and length and a lower proportion of children with morphophysiological values close to the population average ones, as well as a higher family exogamy level estimated on the basis of marriage structure in the parental and preceding generations. The risk of congenital cleft palate and/or cleft lip is considerably increased is the maternal age is older than 35 years or, to a lower degree, if it is younger than 20 years.     

Cleft lip, cleft palate, and velopharyngeal insufficiency

This article provides an introduction to the anatomical and clinical features of the primary deformities associated with unilateral cleft lip-cleft palate, bilateral cleft lip-cleft palate, and cleft palate. The diagnosis and management of secondary velopharyngeal insufficiency are discussed. The accompanying videos demonstrate the features of the cleft lip nasal deformities and reliable surgical techniques for unilateral cleft lip repair, bilateral cleft lip repair, and radical intravelar veloplasty.     

Three-dimensional lip morphometry in adults operated on for cleft lip and palate

Measurements were taken from 18 patients operated on for cleft lip and palate, aged 19 to 27 years, and 162 control subjects matched for sex, age, and ethnic group. Nine soft-tissue landmarks on the lips were digitized by a three-dimensional electromagnetic instrument. From the landmarks, several linear distances (mouth width, philtrum width, vermilion height of upper and lower lip, total vermilion height, total lip height), the interlabial angle, and some areas (vermilion of upper lip, vermilion of lower lip, total vermilion) and volumes (upper lip volume, lower lip volume, total lip volume) were calculated. Patient and reference data were compared by t tests and Watson-Williams tests. In the men, significant differences (p < 0.05) were found in width of the philtrum, height and area of the vermilion part of the upper lip, and total vermilion height and area (all larger in male patients than in controls). In the women, significant differences were found in the height and area of the vermilion part of the upper lip (larger in female patients than in controls), and in the height and area of the vermilion part of the lower lip (smaller in patients than in controls). In both sexes, the interlabial angle was smaller than in the reference population. In conclusion, the upper lip of adult patients operated on for cleft lip and palate differed from that of healthy controls of the same age, sex, and ethnic group. Surgical correction of cleft lip and palate failed to provide a completely normal appearance. The analysis pointed out those parts of the lips and mouth (in particular, the vermilion part of the upper lip) that differed the most from the norm. The method may be used to indicate to the surgeon and patient where additional procedures might be performed to approximate the morphologic characteristics of a reference population.     

Mouse genetic models of cleft lip with or without cleft palate

Nonsyndromic cleft lip and palate (CLP) is among the most common human birth defects. Transmission patterns suggest that the causes are "multifactorial" combinations of genetic and nongenetic factors, mostly distinct from those causing cleft secondary palate (CP). The major etiological factors are largely unknown, and the embryological mechanisms are not well understood. In contrast to CP or neural tube defects (NTD), CLP is uncommon in mouse mutants. Fourteen known mutants or strains express CLP, often as part of a severe syndrome, whereas nonsyndromic CLP is found in two conditional mutants and in two multifactorial models based on a hypomorphic variant with an epigenetic factor. This pattern suggests that human nonsyndromic CLP is likely caused by regulatory and hypomorphic gene variants, and may also involve epigenetics. The developmental pathogenic mechanism varies among mutants and includes deficiencies of growth of the medial, lateral or maxillary facial prominences, defects in the fusion process itself, and shifted midline position of the medial prominences. Several CLP mutants also have NTD, suggesting potential genetic overlap of the traits in humans. The mutants may reflect two interacting sets of genetic signaling pathways: Bmp4, Bmpr1a, Sp8, and Wnt9b may be in one set, and Tcfap2a and Sox11 may be in another. Combining the results of chromosomal linkage studies of unidentified human CLP genes with insights from the mouse models, the following previously unexamined genes are identified as strong candidate genes for causative roles in human nonsyndromic CLP: BMP4, BMPR1B, TFAP2A, SOX4, WNT9B, WNT3, and SP8.     

Maternal effects in human cleft lip and palate.

To look for a persistent maternal effect of CL(P) and CP, 8,000 pedigrees were screened for half sibships, and data were pooled from 16 investigators. After excluding known genetic or cytogenetic diagnoses from the probands with facial clefts, a recurrence risk of .011 was obtained for CL(P) based upon 342 maternal half sibs. This was nearly identical to the risk of .014 based upon 210 paternal half sibs. CP proband frequencies of .004 for maternal half sibs and .009 for the paternal counterparts were also found. The lack of significant maternal effects in this data supports previously reported data from twin studies and from interracial crosses from Hawaii. The lack of maternal effect in human CL(P) and CP is in contrast to genetic data on clefting in mice.