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We report a severe case of Pfeiffer syndrome with an early demise. The mother and her own father had unilateral stub thumb, which was inherited as a coincidental autosomal dominant trait. Although the affected thumb was short, it was not broad and neither family member had any features of Pfeiffer syndrome. We conclude that our patient represents a new Pfeiffer syndrome mutation.

We report on visceral anomalies found in 136 patients with Apert syndrome. Autopsies were only performed on 12 of these cases. Thus, the percentage of anomalies found in our patients should be considered a minimum estimate because of the possibility of clinically silent visceral anomalies, minor internal anomalies, and anatomic variations. Cardiovascular and genitourinary anomalies were found most commonly, occurring in 10% and 9.6%, respectively. As expected, complex and multiple cardiac anomalies were frequently associated with early death. Among genitourinary anomalies, hydronephrosis (3%) and cryptorchidism (4.5%, n = 66 males) occurred most commonly. In contrast, anomalies of the respiratory system (1.5%) and gastrointestinal anomalies (1.5%) occurred with lower frequency. The finding of a solid cartilaginous trachea is particularly important because no case was diagnosed during life but rather, only at autopsy. Because cardiovascular and genitourinary anomalies occur with significant frequency, they should be considered in the workup of all Apert newborn infants. We also recommend MRI study of the trachea in any infant with signs and symptoms of lower respiratory compromise.

A Japanese girl with Pfeiffer syndrome is described. She has clinical and radiological manifestations typical of the syndrome. In addition, she had an imperforate anus not described previously in the syndrome. This seems to expand the phenotype associated with Pfeiffer syndrome or represent a new acrocephalosyndactyly syndrome.

Case reports of seventeen patients with the Saethre-Chötzen syndrome treated at the Stomatology and Maxillofacial Surgery Clinic, Nantes, France are analyzed, together with clinical and paraclinical signs of this syndrome, included within the framework of the acrocephalosyndactylies. Results of cases reported in the published literature are reviewed and compared with those of the present series. The characteristic craniofacial equilibrium of the Saethre-Chötzen syndrome is discussed, together with findings of a teleradiographic study performed according to Delaire's analysis. A discussion on the differential diagnosis of this syndrome is enlarge to include all acrocephalosyndactylies.

Radiographs of the cervical spine--in many cases longitudinal--were available for study in 68 cases of Apert syndrome. Autopsy material was available in one of these cases, and a 3-dimensional reconstruction from a CT scan was also studied in one case. Variable degrees of fusion were observed, involving the articular facets, the neural arch or transverse processes, or block fusion of the vertebral bodies. Ossification may not always be evident in some early radiographs. However, early radiographic signs of impending fusion may be irregularity in vertical orientation of the vertebral bodies and narrowing of the involved intervertebral spaces. Cervical fusions occurred in 68%, single fusions being found in 37%, and multiple fusions in 31%. C5-C6 fusion was most common, alone or in combination with other fusions. In contrast, cervical fusions are known to occur in 25% of Crouzon patients, most commonly involving C2-C3 only. It appears that when fusions are present, C5-C6 involvement in the Apert syndrome and C2-C3 involvement in the Crouzon syndrome separate the 2 conditions in most cases. Because cervical anomalies may complicate an already compromised airway in any form of acrocephalosyndactyly, it is imperative to initiate radiographic study of the cervical spine before undertaking anesthesia for surgery.

Tracheal cartilaginous sleeve (TCS) is a rare congenital malformation in which discrete cartilaginous rings are replaced by a grossly uninterrupted cartilaginous sleeve. Seven previous patients with TCS have been reported in the world literature; in each instance, TCS was associated with craniosynostosis (CS). We report details of five additional patients with TCS, of whom four had a dominantly inherited CS. Gross examination of the available tracheas and bronchi demonstrates a cartilaginous sleeve with posterior interruption but lacking a normal pars membranacea. The stained and cleared tracheas all demonstrate variable ring formation, usually limited to the posterolateral aspect. The functional significance of TCS, if any, is unknown. No data are available on the prevalence of TCS in CS syndromes. The formation of TCS implies a common mesenchymal defect in which normally discrete structures fuse and is probably analogous to other mesenchymal abnormalities seen in these patients.

Cranio-orbito-zygomatic measurements taken from standard axial computed tomographic (CT) scans of unoperated patients with Crouzon syndrome (6 males, 14 females) and Apert syndrome (6 males, 10 females) under 1 year of age were compared to each other and to normal controls (40 males, 35 females). Fifteen cranio-orbito-zygomatic variables were measured and repeated. Means and standard deviations were computed for each sex, and means were pooled since they were not significantly different. Correlation coefficients for repeat measures (intra-observer error) of each variable showed good reproducibility. Only the lateral orbital wall angle differed between the syndromes (p = .034), suggesting that upper facial differences (as measured by these variables) do not manifest themselves at this young age. All measurements for both syndromes, except one, were outside the 95 percent confidence range for age-matched controls. Measurements taken from standard CT scans provide an objective comparison between specific syndromes and the normal population.

As part of an ongoing study of 119 patients with the Apert syndrome, extensive data were available for the analysis of oral manifestations, including mouth shape, lip posture, palatal morphology, dental anomalies, and malocclusion. Findings included a characteristic trapezoidal-shaped mouth. Cleft soft palate or bifid uvula was found in approximately 75%. A Byzantine-arch shaped palate was recorded in almost all patients. Dental anomalies included severely delayed eruption, ectopic eruption, and shovel-shaped incisors. Malocclusion tended to be severe with mesial molar occlusion, mandibular overjet, anterior and posterior crossbites, and severe crowding of teeth. The oral manifestations of Apert syndrome are compared and contrasted with those of Crouzon syndrome.

For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form consists of size and shape. Several approaches for comparing biological forms using landmark data are available. If the two biological forms are demonstrated to be different, the next important issue is to localize the differences by identifying those areas which differ most between the two objects. In this paper we suggest a technique to detect influential landmarks, those which contribute most to the difference between forms. We study the effectiveness of the technique using three-dimensional simulated data sets and two examples. Results suggest that the technique is useful in the study of biological form and its variation.

For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form can be conveniently defined as consisting of size and shape. Several approaches for comparing biological shapes using landmark data are available. Lele (1991a) critically discusses these approaches and proposes a new method based on the Euclidean distance matrix representation of the form of an object. The purpose of this paper is to extend this new methodology to the comparison of groups of objects. We develop the statistical versions of various concepts introduced by Lele (1991a) and use them for developing statistical procedures for testing the hypothesis of shape difference between biological forms. We illustrate the use of this method by studying morphological differences between normal children and those affected with Crouzon and Apert syndromes and craniofacial sexual dimorphism in Cebus apella.

A case of Apert's syndrome with posterior (occipital) encephalocele and absence of corpus callosum is described. This is a rare combination. The mechanisms involved are discussed.

Agenesis of the corpus callosum may be associated with a variety of central nervous system (CNS) and non-CNS abnormalities and is known to occur in a number of specific syndromes. It can be a marker for several inherited metabolic disorders. Study of the Apert syndrome shows a recurrent pattern of CNS abnormalities, including defects of the corpus callosum and limbic structures, megalencephaly, misshapen brain, distortion ventriculomegaly, and gyral anomalies.

The involvement of the lower extremity in acrocephalosyndactyly has received less attention than the craniofacial and upper extremity anomalies. The lower extremity deformities are progressive and require greater attention as the patient grows older. The stiffness of the hips and mild to moderate genu valgum rarely, if ever, require intervention. Foot and toe deformities lead to difficulty with malalignment, painful stresses, and shoe wear. Each of these must be dealt with individually, placing emphasis on the underlying bony abnormality.

The thumb in a child with Apert syndrome provides the key to hand function. The characteristic "hitchhiker" posture or radial clinodactyly of these short but broad digits is caused by an abnormal proximal phalanx. Along with the shortened and radially deviated proximal phalanx, the first webspace (thumb-index) is always deficient. This article details the authors' anatomic observations of these abnormal thumbs and their rationale for treatment.

The surface dysmorphology of the head in Apert syndrome has been known for a century. Recent advances in computer-assisted medical imaging technology allows in vivo nondestructive "dissection." The authors have used this technology to study the subsurface craniofacial dysmorphology of 14 patients with Apert syndrome ranging in age from infancy to adulthood.

This article contains a summary and classification of the major abnormalities seen in both upper and lower extremities associated with Apert syndrome. Whereas rationale and results of treatment of the thumb, hand, foot, shoulder, and elbow can be found in specific articles in this issue, detailed analysis of the anatomy found in the wrist and hand is presented in this article.

We report an infant with Pfeiffer syndrome (acrocephalosyndactyly type V) and a solid cartilaginous trachea lacking rings. This airway abnormality has been reported in a child with Crouzon syndrome but has not been described in Pfeiffer syndrome.

Here we report on a 2 year 3-month-old boy with acrocephalosyndactyly, a bilateral parietooccipital "encephalocele," micropenis, and severe mental retardation. To our knowledge there are no other reports of similarly affected patients in the literature.

An 11-month-old male infant with Saethre-Chotzen syndrome and recurrent respiratory infections is described. Persistent extremely high leukocytosis warranted evaluation of neutrophil functions. It was found that the opsonophagocytic activity was normal, but neutrophil chemotaxis was markedly decreased. Further studies pointed to an intracellular neutrophil defect causing this motility dysfunction.

Apert-Crouzon syndrome (formerly ACS type 2; 10130) is now considered a subset of autosomal dominant Apert acrocephalosyndactyly type 1 (10120), with features of craniosynostoisis, syndactyly of all extremities, maxillary hypoplasia, "parrot-beaked" nose, hypertelorism, exophthalmos, external strabismus, and short upper lip. We report a 3 1/2-month-old infant with features of Apert syndrome, plus thoracic vertebral anomalies radiographically similar to those seen in spondylothoracic dysplasia, a condition in which block thoracic vertebrae with widely open neural arches and a fan-shaped thoracic cage are found. Our patient also had flared metaphyseal ends of humeri, dislocated radii with immobile elbows, an unusual tail-like protuberance in the coccygeal area, and a solid cartilaginous tracheal wall. To date, in ongoing reviews of radiographs of other patients with acrocephalosyndactyly or acrocephalopolysyndactyly complexes and of relevant literature, we have not identified other patients with these findings. The vertebrae and intervertebral discs of the patient in this report, three patients with Jarcho-Levin syndrome, and one with Apert syndrome were measured from anteroposterior chest radiographs; the findings clearly distinguish the condition in our patient from Jarcho-Levin syndrome or Apert syndrome.

The purpose of the paper is to describe and analyze the infant Apert skull with emphasis on the calvaria and its early postnatal development. Skull radiographs of 16 Apert syndrome patients were examined (12 American, 4 Danish; 8 males, 8 females). The criterion for inclusion in the study was that the first skull film had to be obtained before 1 year of age. Study methods employed included plain skull radiographs, roentgencephalometric films in several projections, CT-scans, and 3-D reconstructions. Data from 2 dry skulls and 2 early cases from the literature were also evaluated The following findings were common to all cases during early infancy (less than 3 months): The coronal suture area was prematurely closed and was represented by a bone condensation line beginning at the cranial base, extending upwards, and having a characteristic posterior convexity. Anterior and posterior fontanelles were widely patent. The midline of the calvaria had a gaping defect which extended from the glabellar area to the posterior fontanelle via the metopic suture area, anterior fontanelle, and sagittal suture area. Bony islands of varying sizes were observed in the midline defect. The calvaria was hypomineralized. During the first 2-4 years of life, the midline defect was obliterated by coalescence of the enlarging bony islands without evidence of any proper formation of sutures. The calvaria became thicker with time and several cases developed increased digital markings and enlargement of the sella turcica. During infancy, the Apert skull with its gaping midline defect appears to permit adequate accommodation of the growing brain, albeit distorted in shape. Normal metopic, sagittal, and coronal sutures with interdigitations were not observed in a single instance; in contrast, the lambdoidal sutures appeared normal in all cases. The invariable findings of an extremely short squama and orbital part of the frontal bone together with the posterior convexity of the coronal bone condensation line suggest that growth inhibition in the sphenofrontal and coronal suture area has its onset very early in fetal life.

We reported on thirteen children affected with malformative syndromes associated with mental retardation. MRI examination showed in all of them different types of anomalies; agenesis of corpus callosum, ventricular dilatation and cerebral matter alterations were the most frequent findings. The authors give a brief description of the clinical reports and of the anomalies observed with MRI; they conclude that MRI seems to be a valuable tool especially for the study of the alterations of the cerebral matter and their correlation with mental retardation.

An intergroup comparison of cephalometric landmark configurations by the finite-element method elegantly depicts the algebra of some of the size and shape change measures that one may define by reference to those landmarks. In studies of mean differences between groups, the statistical analysis of these finite elements is equivalent to competent statistical analysis of the same data using any other geometric metaphor, such as properly standardized vector descriptions of landmark "movement" or scalar measures, size and shape variables, taken in sufficient variety. In applications to landmark data, the reality of finite-element depictions is purely statistical rather than phenomenological. In the absence of additional evidence, they should not be held either more or less biologically meaningful than other descriptions of the same landmark changes to which they lead. These propositions are exemplified using landmark data from 13 cases of Apert syndrome.

Twenty craniofacial indices composed of 26 surface measurements taken directly from the head and face were determined in 14 Apert's syndrome patients 18 days to 5 years old (younger subgroup) and 14 patients ages 6 years to 15 years old (older subgroup). All of the patients were North American Caucasians who had undergone early suture release but no facial repair. The indices were compared with those in healthy controls of the same age and sex. The wide intercanthal distance in relation to the narrow soft nose was the most frequent (81.5%) and extensive (17.7% above the maximum normal index value) disproportion. Abnormal indices occurred most often with the combination of one abnormal and one normal measurement (61.0%). All seven of the 16 disproportions seen in both age subgroups increased in frequency nonsignificantly with age: the supernormal cephalic, intercanthal, nasal, and vertical mandibulofacial indices and the subnormal nasofacial, upper face, and jaws' arcs indices. Of the six disproportions that decreased in frequency with age, four changed significantly (the supernormal frontoparietal and frontozygomatic indices and the subnormal mandibulofacial and nasozygomatic indices) and two changed nonsignificantly (the supernormal intercanthoalar and subnormal cheilozygomatic indices). With the exception of two nasal proportions, the extent of the disproportionality decreased in all of the indices that increased with age.

Finite element scaling analysis is used to study differences in morphology between the craniofacial complex of normal individuals and those affected with the syndromes of Apert and Crouzon. Finite element scaling quantifies the differences in shape and size between forms without reference to any fixed, arbitrary registration point or orientation line and measures the amount of form change required to deform one object into another. Two-dimensional coordinates of landmarks digitized from annual sets of cephalometric radiographs were used in the analysis. A simple tabulation shows no difference in variances between the normal and pathological samples. A test of mean differences depicts the Apert and Crouzon morphologies as significantly different from normal. The Apert palate differs from normal in shape in the older age groups analyzed, and palatal size differences are most common at the posterior nasal spine. The Apert pituitary fossa and basi-occiput are significantly larger than normal. The Crouzon pituitary fossa is also larger than normal, but the difference is not always significant. The typical morphology of the Crouzon nose is due more to differences in shape than size. The Crouzon basi-occiput is significantly smaller than normal. An age association of the differences between the normal and pathological craniofacies was found in Apert syndrome but not in Crouzon syndrome. Apert syndrome is characterized by a more homogeneous pattern of craniofacial dysmorphology from 6 months to 18 years of age than Crouzon syndrome.

A 14-year-old boy with conduction hearing loss, acrocephaly, minimum syndactyly, broad thumbs and big toes is classified as being affected with a form of acrocephalosyndactyly, termed Pfeiffer's syndrome (McK+10160) [12]. It is the first case of this syndrome presented in the otorhinolaryngological literature. During exploratory tympanotomy, the ossicular chain was found to be fixed. The incus seemed to be fixed in the epitympanum and there was ankylosis of the stapes. After antrotomy during a first stage, stapedectomy and teflon interposition during a second stage the air-bone gap disappeared. Multidirectional polytomography of the inner ear, performed preoperatively, was normal with the exception of a markedly local bilateral dilatation of the internal acoustic meatus. Although this case is a sporadic one, the mode of inheritance of this syndrome is autosomal dominant.

Biostereometrics is an accurate anthropometric system for quantifying geometric changes of facial form and the relationship of features as they are influenced by growth and by surgery. Facial features distant from the site of surgical intervention are influenced in their geometric relationship to each other by changes in the soft-tissue drape brought about by manipulation of skeletal tissues. The most accurate coordinate system should be elsewhere than on the surface of the face, but if this is not possible it should be in an area farthest removed from the surgical site. This investigation demonstrates that a usable coordinate transformation system can be created by connecting points supernasale and subnasale for establishing the Y Z plane and the construction of the X Z plane at subnasale. Accurate comparative numerical measurements can be made by using soft-tissue landmarks.

Relative mandibular prognathism is an observed finding in Apert and Crouzon syndromes. This imbalance in the facial profile is generally attributed to the diminished growth of the maxilla, thereby increasing the disparity between maxilla and mandible with increasing age. What is not known is whether the mandible is, indeed, normal. Previous work by Kreiborg with Crouzon syndrome led to the conclusion that the mandible, although somewhat smaller, grew in a "normal" pattern. Our own observations, which used a greater variety of mandibular measurements on patients with both Apert and Crouzon syndromes, corroborated Kreiborg 's conclusions but go further to suggest a syndrome-specific mandibular malformation. Ramal height was found equal to the norm and sometimes greater. Mandibular body length was significantly shorter, thereby producing a distinctly different ramus/body length ratio, particularly in older patients. These findings become significant in the planning of reconstructive procedures. They also raise the question as to whether the shape of the mandible is genetic in origin or is an adaptation to the increasing derangements of the cranial base, maxilla, and occlusion observed with maturation in these patients. The possibility of interactive genetic and environmental factors affecting growth of the mandible emerges from the data.

The purpose of this study was to assess long-term position of the maxilla after surgical Le Fort III advancement of midfacial structures in patients with craniosynostosis syndromes. Data from preoperative, short and long-term postoperative lateral head films on 21 consecutive patients with Crouzon's syndrome, Pfeiffer's syndrome, or Apert's syndrome were analyzed. A method of evaluating the position of the postoperative maxilla on lateral head films is described. On average, the position of the maxilla did not change significantly in the postoperative periods studied, although some individual variation was demonstrated. Postoperative management, utilizing a registration bite splint after the intermaxillary fixation has been removed, similar to our treatment following bone grafting procedures in patients with hemifacial microsomia, is described.

The pathologic anatomy of the central nervous system is described in a patient with Apert's syndrome. Multiple developmental anomalies of the brain were noted including disturbances of rhinencephalic organization. The association between maldevelopment of the rhinencephalon and the face is well known. Cranial vault malformations may also be associated with maldevelopment of the rhinencephalon.

Midface advancement by Le Fort III osteotomy is a common procedure in craniofacial surgery. However, little data exist concerning the effect of midface advancement on mandibular growth. This is a retrospective study of 38 patients from two craniofacial centers who had Le Fort III osteotomy. The aims of this investigation were to document the size and shape of the mandible in Crouzon and Apert syndromes and to determine the effect on these parameters of downward and forward movement of the midface. The syndrome patients had increased gonial angle, increased MP-SN, increased ramus height, and increased ratio of ramus height to body length when compared with normal standards. Patients operated during growth and those operated when growth was completed had similar mandibular size and shape indicating that Le Fort III osteotomy had no measurable effect on these parameters. Inclination of the mandible to the anterior cranial base was increased by the operation and remained unchanged during the follow-up period. The results of this study indicate that the size and morphology of the mandible are similar in Crouzon and Apert syndromes. The pattern of growth is more vertical in the syndrome patients than in normals. Le Fort III osteotomy in growing children does not result in altered mandibular size and shape despite backward rotation of the mandible as a result of midface advancement.

The degree of normalization of the shape of the skull was studied in 12 craniosynostosis patients who had been treated with different types of craniotomies in infancy. Three diagnoses were represented: isolated bicoronal synostosis; Crouzon's syndrome; and Apert's syndrome; there were four subjects in each group. Selected cranial dimensions were measured on roentgencephalograms taken in infancy and at follow-up examinations at 2 to 3 years of age. The measurements were compared with control values obtained from patients with cleft lip. Cranial dimensions in the synostosis patients seldom corresponded well with the values of the controls, either before or after surgery. Cranial height, in particular, was increased, especially in patients with Crouzon's or Apert's syndrome. This resulted in modulus values above the control mean for 11 of the 12 patients at the follow-up examinations.