Raised intracranial pressure in Crouzon syndrome: incidence, causes, and management.

OBJECT Patients with Crouzon syndrome (CS) are at risk for developing raised intracranial pressure (ICP), which has the potential to impair both vision and neurocognitive development. For this reason, some experts recommend early prophylactic cranial vault expansion on the basis that if ICP is not currently raised, it is likely to become so. The aim of this study was to examine the justification for such a policy. This was done by analyzing the incidence, causes, and subsequent risk of recurrence in a series of patients with CS, in whom raised ICP was treated only after it had been diagnosed. METHODS This study was a retrospective review of the medical records and imaging data of patients with a clinical diagnosis of CS. RESULTS There were 49 patients in the study, of whom 30 (61.2%) developed at least 1 episode of raised ICP. First episodes occurred at an average age of 1.42 years and were attributable to craniocerebral disproportion/venous hypertension (19 patients), hydrocephalus (8 patients), and airway obstruction (3 patients). They were managed, respectively, by vault expansion, ventriculoperitoneal shunt insertion, and airway improvement. Fourteen of the 30 patients developed a second episode of raised ICP an average of 1.42 years after treatment for their initial episode, and 3 patients developed a third episode an average of 3.15 years after that. Causes of subsequent episodes of raised ICP often differed from previous episodes and required different management. Patients who were < 1 year old when the first episode was diagnosed were at increased risk of recurrence. CONCLUSIONS Although the incidence of raised ICP in CS is high, it did not occur in nearly 40% of children during the course of this study. The several possible causes of CS require different management and may vary from episode to episode. The authors recommend an expectant policy toward these children with careful clinical, ophthalmological, respiratory, and radiological monitoring for raised ICP, reserving intervention for when it has been detected and the appropriate treatment can be initiated.

Foramen magnum size and involvement of its intraoccipital synchondroses in Crouzon syndrome.

BACKGROUND: Cranial sutures and synchondroses tend to close prematurely in patients with Crouzon syndrome. This influences their skull vault and skull base development and may involve in common disturbances such as increased intracranial pressure and cerebellar tonsillar herniation. The authors' hypothesis was that Crouzon patients patients have a smaller foramen magnum than controls because of premature fusion of the intraoccipital synchondroses, putting them at risk for cerebellar tonsillar herniation. Therefore, foramen magnum size and time of intraoccipital synchondroses closure were evaluated and were related to the presence and degree of cerebellar tonsillar herniation. METHODS: The foramen magnum surface area and anteroposterior diameter were measured on three-dimensional computed tomographic scans of 27 Crouzon patients and 27 age-matched controls. Scans had a slice-thickness between 0.75 and 1.25 mm and were aligned in a three-dimensional reformatting platform. The t test was used to study size differences. Synchondroses were graded as described by Madeline and Elster and studied with ordinal logistic regression analysis. RESULTS: Crouzon patients had a smaller foramen magnum surface area (602 mm versus 767 mm, p < 0.001) and anteroposterior diameter (31 mm versus 35 mm, p < 0.001) compared with controls. Differences stayed constant over time. Intraoccipital synchondroses closed 3 to 9 months earlier in Crouzon patients than in controls (p < 0.05). CONCLUSIONS: Since intraoccipital synchondroses close earlier in Crouzon patients, from early life on their foramen magnum is smaller compared with controls. Within Crouzon patients, the presence of cerebellar tonsillar herniation could not be related to foramen magnum size. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Roman arch, keystone fixation for facial bipartition with monobloc distraction.

BACKGROUND: Patients with craniofacial dysostosis may require correction for hypertelorbitism and midface hypoplasia. Traditionally, these procedures were sequential or staged, and used acute advancement with bone grafting and rigid fixation. The authors reviewed a series of combined, one-stage facial bipartition and monobloc distraction procedures using internal devices. They describe the Roman arch, keystone fixation modification to maximize the stability of the bipartition segments and support the vertical load of the distraction forces. METHODS: Patients diagnosed at the University of California, Los Angeles as having craniofacial dysostosis with hypertelorbitism and midface hypoplasia who underwent the Roman arch, keystone fixation procedure were included in the study (n = 13). Reduction of interdacryon and intercanthal distances and the lateral cephalometric horizontal change of the forehead, midface, and maxilla were studied postoperatively and at 1-year follow-up. RESULTS: There were no serious complications (e.g., cerebrospinal fluid leak, meningitis, frontal bone loss); there was a 10 percent rate of total complications (wound infection). Facial bipartition successfully narrowed the interdacryon distance by a mean of 55 percent (21 mm), with only a 3-mm relapse. The mean distraction advancement/relapse was as follows: forehead, +16 mm/-2 mm; midface, 14 mm/-1 mm; and maxilla, 13 mm/-1 mm. Only one of 13 patients required a repeated monobloc procedure. Of the seven patients who reached skeletal maturity, 86 percent underwent a subsequent Le Fort I and/or III procedure. CONCLUSION: The Roman arch, keystone fixation modification of a combined facial bipartition with monobloc distraction using internal devices provided a stable construct for advancement, with minimal relapse.

Síndrome de Crouzon: nuestra experiencia / Crouzon síndrome: our experience

El Síndrome de Crouzon se conoce desde la antigüedad, Homero, el poeta griego, en su obra clásica La Iliada describe un guerrero llamado Tersites…., el hombre más feo fue el que vino de Troya…., su estrecha cabeza…” y esto se conoce como una de las primeras alusiones a las deformidades craneales tipo craneosinostosis. En 1791 logra un paso de avance al plantear que el crecimiento del cráneo ocurre a lo largo de las suturas del calvario y que el fallo en su crecimiento resulta una enfermedad craneal. A pesar de las investigaciones anteriores, no fue hasta 1851 en que Virchow inicia la verdadera etapa científica con un estudio anatómico completo. Pero no es hasta 1912 que se describe por primera vez el Síndrome de Crouzon en una madre y su hija, las mismas presentaban una malformación craneofacial asociada al cierre prematuro de las suturas craneanas(AU)

[Weaver syndrome. 1st case reported in Venezuela]. / Síndrome de Weaver. Primer caso reportado en Venezuela.

A 2 years and 9 months old female patient, with the diagnosis of Weaver syndrome is reported. The proband presents persistent pre and post-natal overgrowth, asynchronic advanced bone age, particular facies, (macrocephaly, ocular hypertelorism, micrognathia, large ears), bilateral widening of the distal femoral metaphysis, bilateral tibia vara, prominent fetal fingerpads, clinodactyly, development delay, low pitched and hoarse cry, nonspecific cortical atrophy, dilation of the ventricles and vermix hypoplasia. The differential diagnosis with other overgrowth syndromes is discussed. The possibility of uniparental disomy and genetic imprinting as the basic genetic defect in the Weaver syndrome is suggested. The patient reported here appears to be the first case in the Venezuelan literature.

Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability.

Mutations have been reported for several craniosynostotic disorders in exon IIIa (exon U or 7) or IIIc (exon B or 9) of the fibroblast growth factor receptor 2 gene (FGFR2). Among the conditions with FGFR2 mutations are two autosomal dominant syndromes, Crouzon and Jackson-Weiss. In this study, 24 Crouzon and one Jackson-Weiss syndrome patients were screened for mutations in the two exons by direct sequencing, and mutations were detected in 28% (7/25) of all cases. Five different mutations were found including two novel (W290G, C342W) and two previously reported, recurrent mutations for Crouzon syndrome (A344A, S354C), and one new mutation for Jackson-Weiss syndrome (C342R). The W290G mutation was found in exon IIIa which is common to both alternatively spliced forms of FGFR2, BEK (expressed predominantly in primordial bones) and KGFR (expressed preferentially in epithelia). Atypical Crouzon syndrome features of epithelial-derived anal and/or external ear anomalies were present in the two affected family members with the mutation. This phenotype possibly reflects the expression of both mutant BEK and KGFR. In addition, the Jackson-Weiss syndrome mutation, C342R, in exon IIIc was observed previously in other craniosynostotic syndromes, Crouzon and Pfeiffer. These results underscore the allelic heterogeneity of these conditions and the complexity of the phenotypic consequences of FGFR2 mutations.

Crouzon syndrome: quantitative assessment of presenting deformity and surgical results based on CT scans.

We reviewed our experience with 14 children who presented sequentially with untreated Crouzon syndrome and whose cranial vault presentation was with bilateral coronal synostosis. Using a method of 14 measurements in the cranio-orbitozygomatic region taken from preoperative and postoperative CT scans in these patients, we documented their presenting skeletal morphology and the results of surgical correction at least 1 year after operation. Our preoperative measurements confirmed a widened anterior cranial vault at 108 percent of normal and a cranial length averaging only 92 percent of normal. In comparison with age-matched controls, orbital measurements revealed a widened anterior interorbital distance at 122 percent of normal, an increased intertemporal width at 121 percent of normal, globe protrusion at 119 percent of normal, and a short medial orbital wall distance at only 86 percent of normal. The distance between the zygomatic buttresses and the interarch distance were found to be increased at 106 and 103 percent of normal, respectively. The zygomatic arch lengths were substantially shortened at only 87 percent of age-matched control values. These findings confirmed clinical observations of brachycephalic anterior cranial vaults with shallow, hyperteloric orbits and globe proptosis. Generally, in these patients the midface is horizontally retrusive and transversely wide, reflected in wide and shortened zygomas. Assessment of the postoperative results at least 1 year later showed no significant changes in any craniofacial measurements. Our findings indicate that early surgical attempts to decompress and reshape the cranio-orbital regions may limit the effects of increased intracranial pressure but do not correct the deformity as judged by CT scan evaluation at least 1 year later. Over the period of the study, the Crouzon deformity did not worsen after surgery, but the measurements remained far from normal.

Birth prevalence studies of the Crouzon syndrome: comparison of direct and indirect methods.

An indirect method for estimating the birth prevalence of the Crouzon syndrome is presented. The fraction of Crouzon syndrome patients in large clinical surveys of all cases of craniosynostosis is calculated and the fractional component obtained is multiplied by the known birth prevalence of craniosynostosis in general. Crouzon syndrome makes up approximately 4.8% of all cases of craniosynostosis. Using a weighted average estimate, birth prevalence was calculated to be 16.5/1,000,000. The results of the indirect method compare favorably with those obtained by the direct method. Nevertheless, because the indirect method is based on a number of assumptions that are easily violated, we cannot recommend its general use except under special circumstances.

Autosomal recessive inheritance in the Setleis bitemporal 'forceps marks' syndrome.

We present the clinical findings in two children with the Setleis bitemporal "forceps marks" syndrome. The striking features include the following: (1) bitemporal scarring, an anomaly that resembles forceps marks; (2) periorbital puffiness with wrinkling of the skin; (3) abnormalities of the eyebrows; (4) anomalies of the eyelashes; (5) flattening of the nasal bridge with a bulbous nasal tip; (6) increased mobility of the skin, associated with severely redundant facial soft tissue; and (7) normal growth and development. The evidence that suggests that this unusual syndrome is inherited in an autosomal recessive fashion includes the following: (1) seven of the patients have come from the relatively isolated towns of San Sebastian and Aguadilla in Puerto Rico; (2) two sets of affected siblings have been described, and, in both cases, the siblings' parents were normal; and (3) one of the children described herein is the product of a consanguineous mating. Although the pathogenetic mechanism is unknown, Setleis syndrome is clearly inherited as an autosomal recessive trait.

Craniofacial surgery: the team approach.

Craniofacial surgery offers a new hope to some grossly deformed people. This complex surgery, which is based on a multidisciplinary team approach, needs to be carefully rationalized and regionalized to facilitate investigation, to improve planning, to reduce the number of complications, and to conserve financial resources. To date the Cranio-Facial Clinic at the Adelaide Children's Hospital and the Royal Adelaide Hospital has reviewed 37 cases and operated upon 13 of these. This work is presented together with a review of the team approach.

The fetal alcohol syndrome.

A specific pattern of malformation involving prenatal-onset growth deficiency, developmental delay, craniofacial anomalies, and limb defects is now recognized in offspring of chronic alcoholic women. Historical evidence suggests that this is not a new observation. A recent French study of 127 offspring of alcoholic mothers indicates that this specific syndrome has been recognized in other parts of the world. Many of the features of this disorder could be related to the kind of malorientation of brain structure seen at the autopsy of one patient described herein. The frequency (43%) of adverse outcome of pregnancy for chronic alcoholic women suggests that serious consideration be given to early termination of pregnancy in severely chronic alcoholic women.