Improved outcome in Pierre Robin sequence: effect of multidisciplinary evaluation and management.

Infants with complications of Pierre Robin sequence are at increased risk of airway obstruction and resultant hypoxia, cor pulmonale, failure to thrive, and cerebral impairment. In an effort to minimize such complications, patients with Pierre Robin sequence were examined prospectively by a multidisciplinary team using polysomnography and continuous oximetry. Obstructive apnea and desaturation occurred in 18 of the 21 patients studied. Four children required only home apnea monitoring, and six required only monitoring and supplemental oxygen. Seven children had lip-tongue adhesion procedures performed, and four required tracheostomy. No patients died. All patients with isolated Pierre Robin sequence had normal development at follow-up except for one child who had experienced a respiratory arrest before referral. With improvements in neonatal intensive care, testing for respiratory assessment, improved surgical and postoperative intervention and home monitoring, the morbidity and mortality for children with Pierre Robin sequence can be reduced markedly.

Abnormal acuity development in infantile esotropia.

Monocular and binocular grating acuities were measured using a swept spatial frequency visual evoked potential (VEP) technique in a group of fifteen infants with esotropia and alternating fixation. Both monocular and binocular acuity measures fell significantly below the mean for age-matched normals. Infants with esotropia and alternating fixation did not have significant interocular acuity differences.

Anomalous motion VEPs in infants and in infantile esotropia.

Visual evoked potentials (VEPs) were recorded monocularly in response to vertical gratings that underwent oscillatory apparent motion at a temporal frequency of 10 Hz. In normal infants 6 months or younger and in patients with a history of constant strabismus onset before 6 months of age, the oscillatory motion VEP contains a prominent first harmonic component that is temporally 180 degrees out of phase in the two eyes. This pattern is not seen in normal adults and is consistent with the presence of a nasalward/temporalward asymmetry of cortical responsiveness in infants and in patients with early onset strabismus.

Facial morphometrics in the identification of gene carriers of X-linked hypohidrotic ectodermal dysplasia.

Roentgenographic measurements and morphometric analysis were employed in the investigation of contrasting patterns of craniofacial variation between normal individuals and those affected by X-linked hypohidrotic ectodermal dysplasia (HED). The research objective was to identify and describe the facial characteristics of heterozygous gene carriers who show minor expression of the disorder. In this study of 13 HED families with 16 affected males, 12 carriers, and 12 normal individuals, affected individuals had at least 3 of the following 4 clinical signs and symptoms: a) hypodontia, b) hypohidrosis, c) hypotrichosis, and d) clinically distinct facial physiognomy. By contrast, the gene carriers manifested only one or 2 or none of the 4 clinical manifestations. In a preliminary comparison of gene carriers vs. normal individuals, we have generated 2 discriminant functions (each based on 3 facial measurements taken either from the lateral or frontal cephalograms). These 2 functions correctly diagnose 100% of the gene carriers and normal HED relatives. Facial anomalies characteristic of the gene carriers were 1) abnormally narrow and short maxillary width and palatal depth dimensions; 2) very small and retrusive malar and maxillary regions; 3) markedly reduced lower facial depth, height and width dimensions; 4) small head height, prominent forehead, and high-set orbits; 5) a generalized, symmetric reduction of the whole craniofacial complex.

Quantitation of craniofacial anomalies in utero: fetal alcohol and Crouzon syndromes and thanatophoric dysplasia.

The study of fetal growth and development by ultrasound has been greatly facilitated in the past few years by the availability of anthropometric standards for the fetal body. Thus, the obstetrician is able to discern between normal and grossly abnormal, and even to quantitate certain fine fetal structures such as the face. This paper presents results obtained from a group of 5 patients referred to the Medical Center from private practices in Indianapolis, Indiana. Prenatal cephalometric analyses by ultrasound suggested the presence of craniofacial anomalies in all 5 cases. However, such defects were not detectable by routine ultrasonographic examination. A clinical examination after birth of each of these 5 patients suggested the following diagnoses: Fetal Alcohol Syndrome (FAS) in 2 individuals, Fetal Alcohol Effects (FAE) in one individual, Crouzon Syndrome (CS) in one patient, and Thanatophoric Dysplasia (TD) in one patient. In order to compare the craniofacial measurement values for each patient to normal standards, we developed Z-Score profiles and Pattern Variability Indexes (PVI) as described by Garn et al. [1984, 1985]. The values presented here support the idea that even mildly abnormal fetal craniofacial patterns are detectable by this relatively new application of ultrasound. At the present time, no conclusions can be made regarding the diagnostic accuracy of these patterns and profiles. However, the potential value of fetal cephalometry for documenting craniofacial dysmorphology is clearly indicated.

Probable autosomal recessive inheritance of polysplenia, situs inversus and cardiac defects in an Amish family.

We report on an Amish family with five individuals in two generations with complex congenital heart disease. Autopsy findings in one and clinical examination in the others support the diagnosis of polysplenia "syndrome." In a mouse model, this spectrum of situs abnormalities and cardiovascular defects shows recessive inheritance with homozygotes having either situs solitus or situs inversus or ambiguous situs. The parents of the four affected sibs are fourth cousins. We think that the father of these four children is an affected but clinically normal homozygote, that his deceased sister was an affected homozygote, and it seems likely that they too had consanguinous parents.

Cephalometric evidence for a dominantly inherited predisposition to cleft lip-cleft palate in a single large kindred.

Several studies have demonstrated an association between facial shape in parents and the presence of oral clefts in their offspring. However, these observations have been of little practical value because it has been assumed that facial shape was just one predisposing component among many in a multifactorial model of inheritance. Cephalometric analysis of a large family with 5 generations of affected individuals suggests that facial shape can be used to identify presumed carriers of a major gene associated with an increased risk for oral clefts. Discriminant function analysis indicates that such at risk individuals can be recognized effectively through a combination of increased midfacial and nasal cavity widths, reduced facial height, and a flat facial profile. The ability to identify minimally affected gene carriers within families would provide critical information needed in the search for molecular markers that segregate with the genetic risk for clefting.

Gingival fibromatosis with sensorineural hearing loss: an autosomal dominant trait.

Gingival fibromatosis is a heterogeneous entity that can occur both as a part of syndromes and as an isolated trait. We describe the second family with a rare, dominantly inherited syndrome of gingival fibromatosis and progressive sensorineural hearing loss.

Antley-Bixler syndrome from a prognostic perspective: report of a case and review of the literature.

The Antley-Bixler syndrome (ABS) is characterized by craniosynostosis, radiohumeral synostosis, and femoral bowing. Other findings include a trapezoid-shaped head, deformed ears, severe midface hypoplasia, choanal atresia or stenosis, and long bone fractures. Most ABS cases have died in the first months of life from respiratory complications. The poor prognosis in this condition makes counseling difficult and early termination of pregnancy a consideration. The medical and surgical management information presented here can be used as a guide for counseling parents in the future. We report on a new patient with ABS who now at age 3 yr, has been followed by the medical staff of Riley Children's Hospital since birth. She has had successful medical and surgical management. Although the multisynostoses seen in this disorder is undoubtedly related to the soft tissue malformations such as choanal stenosis and midface hypoplasia, the cause remains unknown. The literature is also reviewed in this condition.

Cleft lip+/-cleft palate: an overview of the literature and an analysis of Danish cases born between 1941 and 1968.

In recent years there has been some controversy over the analytical designs and the meaning of varying results with regard to studies of facial clefting and other common congenital malformations. Regardless, it is still unclear as to the nature of the genetic and environmental components of the etiology as well as the nature of the relevant pathogenetic mechanisms. Despite claims to the contrary, the predictions of a particular multifactorial/threshold inheritance (MF/T) model delineated by Carter [1977d] and others are not well supported by studies worldwide. The present study population consists of 1,895 persons born in Denmark with cleft lip with or without cleft palate (CL +/- P) between 1941 and 1968. A test of the MF/T predictions revealed the following: 1) the incidence of CL +/- P in siblings was 40 X greater than that in the general population 2) the risk to siblings of CL +/- P females was not significantly different from the risk to siblings of CL +/- P males; 3) recurrence risk for siblings of CL +/- P probands was dependent upon the proband's cleft type; 4) only 0.4% of the variation in risk to the siblings born after the proband could be accounted for by the number of previously affected siblings; 5) the consanguinity rate was 6 times less than the general population rate; 6) heritability estimates from siblings and parents by sex suggest, either the presence of significant dominance effects, or a common sibling environment component in the etiology of the disorder. Further, testing with a multiple-sex threshold method, designed and provided us by [Kidd and Spence, 1976] revealed that neither the MF/T nor single-major locus with random environmental variation provided a good fit. In light of recent experimental mouse and human data, an alternative model of monogenic-dependent susceptibility to a variety of teratogens is discussed.

Cephalometric analysis of families with dominantly inherited Crouzon syndrome: an aid to diagnosis in family studies.

Crouzon syndrome (CS) is an autosomal dominant condition comprising orbital proptosis, midfacial hypoplasia, premature sutural synostosis, and altered proportions of bone lengths in the hands. In families the CS trait is highly variable. Several cases of affected sibs born to unaffected parents have been explained by germinal mosaicism. We hypothesized that cephalometric and metacarpophalangeal analysis may help to classify affected and unaffected subjects within families when clinical diagnosis is difficult. Posterior-anterior and lateral cephalometric radiographs and hand films were taken of 10 CS patients and 18 unaffected relatives. Sixty-two craniofacial and 19 hand linear and angular measurements were made on each subject and standardized by conversion to z-scores using published normal standards. Ten craniofacial variables were selected for use in a stepwise forward discriminant function analysis to develop an equation which could be used to discriminate CS patients from normal subjects. A two-group discriminant function using four craniofacial variables and one hand variable correctly classified the CS patients and relatives 100% of the time. The results suggest that relatively few facial variables are needed to differentiate most cases of CS but the addition of one or more hand variables may increase the sensitivity. DNA testing is necessary to adequately demonstrate incomplete penetrance in CS, but pretesting subjects for molecular studies using these methods may improve results.

Bone dysplasias: the prenatal diagnostic challenge.

The prenatal diagnosis of bone dysplasias presents difficult challenges for the clinician involved in monitoring pregnancies. Such diagnoses highlight delicate ethical issues and may require difficult decision-making when the differential diagnosis includes a lethal bone dysplasia. Despite the rapid technological advances in ultrasonography, the ability to make prenatal diagnoses within this group of disorders is limited by the restricted ultrasonographic capability to appreciate fully the detailed fetal anatomy. However, we perceive that a significant further limitation involves the lack of a systematic protocol to guide the clinician in the ultrasonographic evaluation of a fetus suspected of having a skeletal dysplasia. In an attempt to aid the clinician who is evaluating these suspected pregnancies, we report here 8 cases and propose a model protocol for the ultrasonographic diagnostic approach to fetal skeletal problems in utero.

The syndrome of multisynostotic osteodysgenesis with long-bone fractures.

Described here are two patients with a newly recognized syndrome of bone and cartilage maldevelopment which, we believe, results from a single embryonic defect, probably of genetic origin. The cardinal manifestations of this association are craniosynostosis, radiohumeral synostosis (RHS), and femoral bowing. Specific secondary defects include midface hypoplasia with characteristic facial appearance and ears, neonatal femoral fractures, and multiple minor anomalies of the limbs. Though the differential diagnosis includes such disorders as the campomelic syndrome, osteogenesis imperfecta (OI) and certain of acrocephalosyndactyly syndromes, the unique combination of clinical and radiographic abnormalities allows ready differentiation. The cause cannot be determined from these two cases.

A survey of vision screening policy of preschool children in the United States.

A state-by-state survey regarding preschool vision screening guidelines, policies, and procedures was conducted. Currently 34 states provide vision screening guidelines and 15 states require vision screening of at least some of their preschool-aged children. The Department of Public Health administers the programs in 26 states, the Department of Education in 13. A wide range of professional and lay personnel conduct preschool vision screenings, and nurses participate in the screening process in 22 states. Visual acuity is assessed in 30 states, eye alignment in 24 states, refractive error in eight states, and color vision in 10 states. A combination of screening tests is recommended in 24 states. Currently, 45 states do not require screening of all preschool children. Thus, although laws, guidelines, and recommendations exist in most states, many preschool-age children do not have access to vision screening programs.

Fetal craniofacial morphometrics: in utero evaluation at 16 weeks' gestation.

Although ultrasound has proved useful in the diagnosis of fetal craniofacial malformations, its success has been based primarily on subjective clinical observations of apparent abnormal fetal structures, their proportions, and unusual features. However, such clinical observations may be misleading and ideally should be validated by standardized quantitative measurements. We describe here an ultrasonographic methodology that has provided quantitative data describing the normal fetal craniofacies at 16 weeks of gestation. This report is part of an ongoing research project directed at describing fetal facial morphology in utero at different gestational ages. Such data can be used to construct growth curves to which observations from suspected abnormal fetuses can be compared. A total of 53 patients were evaluated at 16 weeks of gestation, at which time 24 craniofacial linear and angular measurements were made. The landmarks employed for these measurements were those used in roentgencephalometry so that this fetal data base could be related to postnatal populations. Such data will contribute not only to a description of facial dysmorphogenesis but also to a better understanding of normal facial growth and development. Furthermore, they constitute a useful tool for prenatal diagnosis, gestational aging, growth predictions, and perhaps for as yet relatively unexplored fields such as fetal therapy.

Plasticity of human motion processing mechanisms following surgery for infantile esotropia.

Monocular oscillatory-motion visual evoked potentials (VEPs) were measured in prospective and retrospective groups of infantile esotropia patients who had been aligned surgically at different ages. A nasalward-temporal response bias that is present prior to surgery was reduced below pre-surgery levels in the prospective group. Patients in the retrospective group who had been aligned before 2 yr of age showed lower levels of response asymmetry than those who were aligned after age 2. The data imply that binocular motion processing mechanisms in infantile esotropia patients are capable of some degree of recovery, and that this plasticity is restricted to a critical period of visual development.

Oral manifestations of acute leukemia in children.

Seventy-seven children with acute leukemia were examined. A wide spectrum of oral findings was observed as the consequence of direct leukemic infiltration of tissue, infection resulting from bone marrow and immunosuppression, impaired healing responses, and poor oral hygiene. Guidelines for dental treatment are provided.

The oral-facial geneticist: his training and role in dentistry.

There is a great need today for clinical geneticists who can diagnose hereditary malformation complexes and counsel afflicted patients and their families. The vast majority of these heritable syndromes have significant expression in the oral-craniofacial complex. This paper describes the minimal qualifications and training needed by postgraduate dentists to function as oral-facial geneticists. The oral-facial geneticist is defined as a human geneticist who has special interest and training in diseases of the oral-facial complex. In addition to patient care and consultation, persons with such training may make important contributions to teaching and research in cranio-facial growth and development.