A case with bilateral radio-ulnar synostosis

Congenital radio-ulnar synostosis may be an isolated abnormality or additional abnormalities may accompany it. It may also be found as a part of well-known syndromes. We present a case with bilateral congenital radio-ulnar synostosis, speech delay, dimple on shoulders, café au lait spot and characteristic facial appearance. The proband has a brother with similar clinical findings with the exception of congenital radio-ulnar synostosis. We discuss the possible relationship between our case and previously described syndromes with congenital radio-ulnar synostosis, and distinct phenotypic features of the presented case.     

Lambdoid synostosis: surgical considerations

Premature closure of the lambdoid suture may result in abnormalities in skull shape not only in the parieto-occipital region, but also in the frontal region and at the vertex of the skull. Although most of these abnormalities are mild, some constitute significant abnormalities in shape and therefore require specific surgical correction. In this report, we describe our approach from five patients we have treated and followed for 6 to 24 months with abnormalities characteristic of unilateral and bilateral lambdoid synostosis. We describe our approach to the simultaneous correction of frontal, occipital, and abnormal vertical height skeletal abnormalities in one operative procedure. To date, no negative neurologic sequelae have resulted from this operative approach, but significant improvement in skull form has been appreciated.     

Molecular diagnosis of bilateral coronal synostosis.

The authors performed a prospective study evaluating molecular diagnosis in patients with bilateral coronal synostosis. The patients were divided into two groups: (1) those clinically classified as having Apert, Crouzon, or Pfeiffer syndrome and (2) those clinically unclassified and labeled as having brachycephaly. Blood samples were drawn for genomic DNA analysis from 57 patients from 1995 to 1997. Polymerase chain reactions were performed using primers flanking exons in FGFR 1, 2, and 3. Each exon was screened for mutations using single-strand confirmation polymorphism, and mutations were identified by DNA sequencing. Mutations in FGFR2 or FGFR3 were found in all patients (n = 38) assigned a phenotypic (eponymous) diagnosis. All Apert syndrome patients (n = 13) carried one of the two known point mutations in exon 7 of FGFR2 (Ser252Trp and Pro253Arg). Twenty-five patients were diagnosed as having either Crouzon or Pfeiffer syndrome. Five patients with Crouzon syndrome of variable severity had mutations in exon 7 of FGFR2. Fifteen patients (12 with Crouzon, 3 with Pfeiffer) had a mutation in exon 9 of FGFR2, many of which involved loss or gain of a cysteine residue. A wide phenotypic range was observed in patients with identical mutations, including those involving cysteine. Two patients labeled as having Crouzon syndrome had the Pro250Arg mutation in exon 7 of FGFR3. All three patients with the crouzonoid phenotype and acanthosis nigricans had the same mutation in exon 10 of FGFR3 (Ala391Glu). This is a distinct disorder, characterized by jugular foraminal stenosis, Chiari I anomaly, and intracranial venous hypertension. Mutations were found in 14 of 19 clinically unclassifiable patients. Three mutations were in exon 9, and one was in the donor splice site of intron 9 on FGFR2. The most common mutation discovered in this group was Pro250Arg in exon 7 of FGFR3. These patients (n = 10) had either bilateral or unilateral coronal synostosis, minimal midfacial hypoplasia with class I or class II occlusion, and minor brachysyndactyly. No mutations in FGFR 1, 2, or 3 were detected in five patients with nonspecific brachycephaly. In conclusion, a molecular diagnosis was possible in all patients (n = 38) given a phenotypic (eponymous) diagnosis. Different phenotypes observed with identical mutations probably resulted from modulation by their genetic background. A molecular diagnosis was made in 74 percent of the 19 unclassified patients in this series; all mutations were in FGFR2 or FGFR3. Our data and those of other investigators suggest that we should begin integrating molecular diagnosis with phenotypic diagnosis of craniosynostoses in studies of natural history and dysmorphology and in analyses of surgical results.     

Molecular analysis of patients with synostotic frontal plagiocephaly (unilateral coronal synostosis)

Mutations in genes known to be responsible for most of the recognizable syndromes associated with bilateral coronal synostosis can be detected by molecular testing. The genetic alterations that could cause unilateral coronal synostosis are more elusive. It is recognized that FGFR and TWIST mutations can give rise to either bilateral or unilateral coronal synostosis, even in the same family. The authors undertook a prospective study of patients presenting with synostotic frontal plagiocephaly (unilateral coronal synostosis) to Children's Hospital Boston during the period from 1997 to 2000. Mutational analysis was performed on all patients and on selected parents whenever familial transmission was suspected. Intraoperative anthropometry was used in an effort to differentiate those patients in whom a mutation was detected from those in whom it was not. The anthropometric measures included bilateral sagittal orbital-globe distance, inter medial canthal distance, and nasal angulation. Macrocephaly and palpebral angulation were also considered possible determinants. There was a 2:1 female preponderance in 47 patients with synostotic frontal plagiocephaly. Mutations were found in eight of 47 patients: two patients with different single-amino-acid changes in FGFR2, three patients with FGFR3 Pro250Arg, and three patients with TWIST mutations. Another patient had craniofrontonasal syndrome for which a causative locus has been mapped to chromosome X, although molecular testing is not yet available. Two features were strongly associated with a detectable mutation in patients with synostotic frontal plagiocephaly: asymmetrical brachycephaly (retrusion of both supraorbital rims) and orbital hypertelorism. Other abnormalities in the craniofacial region and extremities were clues to a particular mutation in FGFR2, FGFR3, TWIST, or the X-linked mutation. Neither macrocephaly nor degree of nasal angulation nor relative vertical position of the lateral canthi correlated with mutational detection. An additional four patients in this study had either unilateral or bilateral coronal synostosis in an immediate relative and had anthropometric findings that predicted a mutation, and yet no genetic alteration was found. This suggests either that the authors' screening methods were not sufficiently sensitive or that perhaps there are other unknown pathogenic loci. Nevertheless, molecular testing is recommended for infants who have unilateral coronal synostosis, particularly if there are the anthropometric findings highlighted in this study or an otherwise suspicious feature in the child or a parent. Infants with either an identified or a suspected mutation usually need bilateral asymmetric advancement of the bandeau and may be more likely to require frontal revision in childhood.     

Humeroradial synostosis

Summary A 1-year-old female child with congenital humeroradial synostosis, who also had microphthalmia and coloboma of the iris and choroidea is described. This is the second case in the literature in which chromosomal studies have revealed no abnormalities. Dermatoglyphic studies are also described.     

Preoperative anthropometric dysmorphology in metopic synostosis

Anthropometric identification of dysmorphology in craniofacial anomalies, including the craniosynostoses, provides invaluable assistance in clinical diagnosis as well as offering a technique for interpreting possible deformities in skeletal remains. Premature closure of the metopic suture is a rare form of craniosynostosis, representing about 4% of clinically diagnosed synostoses. Accompanying this closure are defects of the head and face, particularly the upper face and orbits. To identify quantitatively the craniofacial dysmorphology associated with metopic synostosis, 50 patients with a diagnosis of primary (nonsyndromal) metopic synostosis were examined using a battery of 24 anthropometric measurements from which 11 proportion indices were calculated. The data were compared to sex- and age-matched normal standards and converted to standard (Z) scores before being analyzed using Student's t-test. The data indicate a complex pattern of dysmorphology arising from the synostosis which affects the upper face and orbits as well as the cranial vault. The entire fronto-orbito-zygomatic complex is narrowed, and vertex is reduced. There is compensatory sagittal and transverse growth of the posterior neurocranium and compensatory vertical and sagittal growth of the upper face. There are statistically significant differences in the pattern of dysmorphology between patients presenting prior to 6 months of age and those older but no significant differences between sexes. Am J Phys Anthropol 103:341–351, 1997. © 1997 Wiley-Liss, Inc.     

Experimental unilateral coronal synostosis in rabbits

Immobilization of the coronal suture was produced unilaterally in 9-day-old rabbits to determine its effect on subsequent craniofacial development. The suture was immobilized unilaterally by the topical application of methylcyanoacrylate adhesive. Subsequent growth effects on the cranial vault, base, and facial skeleton were assessed by serial radiographic cephalometry. Unilateral coronal suture immobilization resulted in significantly decreased bone growth at the coronal suture (mean 0.95 mm +/- 0.35 SE) when compared to sham-treated control animals (mean 5.06 mm +/- 0.20 SE). Frontonasal suture bone growth contralateral to the immobilized half of the coronal suture, however, was significantly increased. The anterior cranial base became significantly shortened, and orbital asymmetry developed. The pattern of induced abnormalities simulates unilateral coronal synostosis in humans.     

Metopic synostosis: Defining the temporal sequence of normal suture fusion and differentiating it from synostosis on the basis of computed tomography images

Only the metopic suture normally fuses during early childhood; all other cranial sutures normally fuse much later in life. Despite this, metopic synostosis is one of the least common forms of craniosynostosis. The temporal sequence of normal physiologic metopic suture fusion remains undefined and controversial. Therefore, diagnosis of metopic synostosis on the basis of computed tomography images alone can prove misleading. The present study sought to determine the normal sequence of metopic suture fusion and characterize both endocranial and ectocranial suture morphology. An analysis of computed tomography scans of 76 trauma patients, ranging in age from 10 days to 18 months, provided normative craniofacial data that could be compared to similar data obtained from the preoperative computed tomography scans of 30 patients who had undergone surgical treatment for metopic synostosis. Metopic suture fusion was complete by 6 to 8 months in all nonsynostotic patients, with initiation of suture fusion evident as early as 3 months of age. Fusion was found to commence at the nasion, proceed superiorly in progressive fashion, and conclude at the anterior fontanelle. Although an endocranial ridge was not commonly seen in synostotic patients, an endocranial metopic notch was virtually diagnostic of premature suture fusion and was seen in 93 percent of synostotic patients. A metopic notch was not seen in any nonsynostotic patient. The morphologic and normative craniofacial data presented permit diagnosis of metopic synostosis based on computed tomography images obtained beyond the normal fusion period.     

Duration of synostosis of the ischiopubic synchondrosis]

A table of the developmental rate of synostosing pubic-ischiatic synchondrosis is made on the basis of analysis of 305 pelvis roentgenograms of children from 2 till 14 years of age. The obtained data may be used in clinical differential diagnosing between such process and osteochondropathy of pubic-ischiatic synchondrosis as well as for determining the bone age of children     

Metacarpal synostosis: a simple classification and a new treatment technique

The current classification of metacarpal synostosis is based on the extent of the synostosis. The authors propose a new classification that takes into account the shape of the metacarpal bones, the curvature of the epiphysis, and the discrepancy in length between the two bones. This classification provides better guidelines for the correction of all components of the deformity. The classification is based on the authors' observations of and experience with 36 cases of metacarpal synostosis; 13 of the deformities were surgically corrected. The I-shaped deformity, whether with distinct (type d) or fused (type f) metacarpophalangeal joints, does not require surgical correction. The U-shaped deformity has parallel epiphysis and does not require surgery unless the two metacarpals are asymmetrical in length (type a) or tightly fused (type t); in these cases, simple lengthening or widening of the space with a bone graft is sufficient. Y-shaped synostosis should be separated whether the branches are symmetrical or asymmetrical, the latter having one branch shorter than the other. Because the epiphyses are already divergent, simple separation does not effectively correct Y-shaped synostosis. The authors propose an osteotomy to isolate a trapezoidal segment of bone from the bifurcation. The isolated bone segment is then reversed in the proximal-distal direction to provide a "plateau" upon which the two distal metacarpals can be realigned. Two cases of Ys (symmetrical) synostosis were successfully treated with this technique; one case of Ya (asymmetrical) synostosis also required distraction lengthening of the shorter metacarpal to achieve an excellent result. One of the most difficult types of metacarpal synostosis to treat is k-shaped synostosis, observed only between the fourth and fifth metacarpals; in this type, the head of the short fifth metacarpal abuts the metaphysis of the fourth. Osteotomy and distraction lengthening provide predictable results for correction of this deformity. The authors suggest that k-shaped synostosis might represent a late evolution of untreated Ua synostosis.     

Neurodevelopment in children with single-suture craniosynostosis and plagiocephaly without synostosis.

The objective of this study was to determine whether children with nonsyndromic craniosynostosis and plagiocephaly without synostosis demonstrated cognitive and psychomotor delays when compared with a standardized population sample. This was the initial assessment of a larger prospective study, which involved 21 subjects with nonsyndromic craniosynostosis (mean age, 10.9 months) and 42 subjects with plagiocephaly without synostosis (mean age, 8.4 months). Each child was assessed using the Bayley Scales of Infant Development-II (BSID-II) for cognitive and psychomotor development before therapeutic intervention (surgery for craniosynostosis and molding-helmet therapy for plagiocephaly without synostosis). The distribution of the scores was divided into four groups: accelerated, normal, mild delay, and significant delay. The distributions of the mental developmental index (MDI) and the psychomotor developmental index (PDI) were then compared with a standardized Bayley's age-matched population, using Fisher's exact chi-square test. Within the craniosynostosis group, the PDI scores were significantly different from the standardized distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the craniosynostosis group were accelerated, 43 percent were normal, 48 percent had mild delay, and 9 percent had significant delay. In contrast, the MDI scores were not statistically different (p = 0.08). Within the group with plagiocephaly without synostosis, both the PDI and MDI scores were significantly different from the normal curve distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the group with plagiocephaly without synostosis were accelerated, 67 percent were normal, 20 percent had mild delay, and 13 percent had significant delay. With regard to the MDI scores, 0 percent of the subjects in this group were accelerated, 83 percent were normal, 8 percent had mild delay and 9 percent had significant delay. This study indicates that before any intervention, subjects with single-suture syndromic craniosynostosis and plagiocephaly without synostosis demonstrate delays in cognitive and psychomotor development. Continued postintervention assessments are needed to determine whether these developmental delays can be ameliorated with treatment.     

Photographic assessment of head shape following sagittal synostosis surgery.

A photographic assessment of the head shape of infants who had undergone surgical correction of sagittal synostosis was performed to determine (a) whether this subset could be delineated from an age-matched normal subpopulation and (b) whether two operative procedures differed in achieving normalization of head shape. This retrospective study included 8 patients who underwent extended strip craniectomy, 12 patients who underwent subtotal calvarectomy and cranial vault remodeling, and 12 age-matched subjects with no calvarial abnormality, for a total of 32 subjects. Criteria for inclusion in this study included surgery for sagittal synostosis within the first year of life and postoperative photographs at ages 4 to 8 years (mean, 4.5 years). Each set of images (frontal and lateral profile) were ranked from most to least normal by five lay observers and four professional observers. The rankings were analyzed with statistics designed for ordinal data. Differences in ranking between treatment groups were examined with Kruskal-Wallis rank sums tests. Mean ranks were calculated for lay and professional observers in an attempt to produce simpler and more generalizable results; these means were also analyzed using statistics designed for ordinal data. There was no statistical difference in the ranks of infants who had undergone a surgical correction and the normal subpopulation. In the mean rankings of the lay observers, the normal groups had the highest score mean (15.6), the group with extended strip craniectomy was second (16.0), and the subtotal calvarectomy with calvarial remodeling group was last (17.8) (p = 0.84). In the mean rankings of the professional observers, the normal groups again had the highest score mean (15.8), the subtotal calvarectomy group was second (15.9), and the extended craniectomy group was last (18.6) (p = 0.77). These results suggest that children who have undergone correction of sagittal synostosis in infancy are indistinguishable from their peers, on the basis of fully haired head shape on frontal and lateral photographs, when they begin primary school, irrespective of the type of calvarial surgery.     

Pubic symphyseal synostosis and sexual dimorphism of the pelvis inPresbytis cristata andPresbytis rubicunda

This study examines the relationship between public symphyseal synostosis and sexual dimorphism of the pelvis in two sympatric species ofPresbytis—P. cristata andP. rubicunda. Whereas no specimen ofP. cristata shows fusion of the interpubic joint, a high percentage of female (43.8%) and male (83.3%)P. rubicunda have a fused public symphysis. As females of both species are similar in body size, they are predicted to give birth to similarly sized newborns. Based on comparison with other anthropoids, the percentage dimorphism in the ischiopubic index inP. cristata andP. rubicuda suggests selection on pelvic capacity in relation to obstetrics. In species characterized by cephalopelvic constriction (i.e., the size of the fetal cranium closely approximates the capacity of the maternal birth canal), successful birth seems possible only by a hormonally induced increase in pelvic joint mobility during delivery. However, fusion of the interpubic joint obviates pelvic joint mobility. Consequently, this study tests the hypothesis thatP. rubicunda shows obstetric adaptations of the pelvis that are not found inP. cristata. The results show that pelvic capacity is larger in females than males in bothP. cristata andP. rubicunda; the sexual difference is most pronounced at the inlet. Moreover, the pattern of pelvic dimorphism is nearly identical between the species. When females of the two species are compared,P. rubicunda evidences a shorter distance between the sacroiliac and hip joints and a wider bituberous diameter. The former is related to interspecific differences in locomotion, and the latter is associated with obstetrics.