Alternative titles; symbols. Other entities represented in this entry:. Crouzon syndrome and Pfeiffer syndrome are allelic disorders with overlapping features. Apert syndrome is a congenital disorder characterized primarily by craniosynostosis, midface hypoplasia, and syndactyly of the hands and feet with a tendency to fusion of bony structures.

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Alternative titles; symbols. Other entities represented in this entry:. Crouzon syndrome and Pfeiffer syndrome are allelic disorders with overlapping features.

Apert syndrome is a congenital disorder characterized primarily by craniosynostosis, midface hypoplasia, and syndactyly of the hands and feet with a tendency to fusion of bony structures. Most cases are sporadic, but autosomal dominant inheritance has been reported Mantilla-Capacho et al. Cohen provided a review of all the 'craniosynostosis syndromes.

Apert defined a syndrome comprising skull malformation characterized by acrocephaly of brachysphenocephalic type and syndactyly of the hands and feet with complete distal fusion with a tendency to fusion of bony structures. The hand, when all the fingers are webbed, has been compared to a spoon and, when the thumb is free, to an obstetric hand. Blank assembled case material on 54 patients with Apert syndrome born in Great Britain. Two clinical categories were distinguished: 1 'typical' acrocephalosyndactyly, to which Apert's name is appropriately applied; and 2 other forms lumped together as 'atypical' acrocephalosyndactyly.

The feature distinguishing the 2 types is a middigital hand mass with a single nail common to digits , found in Apert syndrome and lacking in the others. Thirty-nine of the 54 were of Apert type. Six of 12 autopsies showed visceral anomalies, but in none were these identical.

Schauerte and St-Aubin pointed out that progressive synostosis in Apert syndrome occurs in the feet, hands, carpus, tarsus, cervical vertebrae, and skull, and proposed 'progressive synosteosis with syndactyly' as a more appropriate designation. In a report on Crouzon disease, Dodge et al. Most conclude that this disorder is actually Apert syndrome with unusually marked facial features Temtamy and McKusick, Kreiborg et al.

C5-C6 fusion was most common. Radiographic study of the cervical spine is imperative before undertaking anesthesia for surgery in these patients. Wilkie et al. In the Apert hand, the central 3 digits are always syndactylous; in the least severe instance, type 1, the thumb and part of the fifth finger are separate from the syndactylous mass; in type 2, the little finger is not separate; and in type 3, the thumb and all fingers are included.

Similarly, syndactyly in the foot may involve mainly the 3 lateral digits type 1 or digits with a separate big toe type 2 , or be continuous type 3. Cohen and Kreiborg studied 44 pairs of hands and 37 pairs of feet in Apert syndrome, using clinical, dermatoglyphic, and radiographic methods. They also studied histologic sections of the hand from a week stillborn fetus.

They noted that in general the upper limb is more severely affected than the lower limb. Coalition of distal phalanges and synonychia found in the hands was never present in the feet. Varying degrees of mental deficiency have been associated with Apert syndrome; however, individuals with normal intelligence have also been reported.

Individuals who have craniectomy early in life may have improved intelligence. Patton et al. Early craniectomy did not appear to improve intellectual outcome. Six of 7 school drop-outs with normal or borderline intelligence were in full-time employment or vocational training. Contrary to early conclusions such as that of Park and Powers , Cohen and Kreiborg concluded that many patients with Apert syndrome are mentally retarded. They had information on 30 patients with malformations of the corpus callosum, the limbic structures, or both, and suggested that these malformations may be responsible for mental retardation.

Progressive hydrocephalus seemed to be uncommon and was frequently confused with nonprogressive ventriculomegaly. Cinalli et al. Only 1. In reviewing their series of 70 children with Apert syndrome, Reiner et al. Malformations of the corpus callosum and ventricular size did not correlate with the final IQ, whereas anomalies of the septum pellucidum did. The third significant factor in intellectual achievement was the setting in which the children were raised. IQ was normal in Pelz et al.

Cohen and Kreiborg commented on the cutaneous manifestations in a series of cases of Apert syndrome Cohen and Kreiborg, Hyperhidrosis was found in all patients. The skin became oily at adolescence and thereafter, with acniform lesions on the face, chest, back, and upper arms.

The authors commented on and illustrated the phenomenon of 'interrupted eyebrows,' which may be due to the underlying bony defect. The orbital plate of the frontal bone is very short, resulting in early fusion of the sphenoparietal suture. This leads to marked retrusion and elevation of the supraorbital wings, most pronounced laterally. Interruption of the eyebrows corresponds to this defect. Several patients had excessive skin wrinkling of the forehead.

Maroteaux and Fonfria reported a patient with seemingly typical Apert syndrome except for the presence of postaxial polydactyly of the hands and preaxial polydactyly of the feet. The authors could not discern whether the findings represented a low frequency feature of Apert syndrome or a distinct syndrome. Sidhu and Deshmukh reported a somewhat similar case in the child of a first-cousin couple.

However, Gorlin doubted the existence of a separate recessive entity and stated that polysyndactyly in the feet, especially replication of metatarsals, is not rare in Apert syndrome. Lefort et al. The authors suggested that 'acrocephalosyndactyly' versus 'acrocephalopolysyndactyly' represents a pseudodistinction and that use of these terms should be discontinued.

Mantilla-Capacho et al. She did not have cleft palate. The authors noted that only 8 patients with Apert syndrome and polydactyly had been reported, and that their case was the first confirmed by genetic analysis.

In a review of cranial imaging in 30 patients with Apert syndrome, Quintero-Rivera et al. In addition, 21 patients had abnormal semicircular canals, 28 had jugular foraminal stenosis, 5 patients had Chiari I malformation, 5 had low-lying cerebellar tonsils, and 2 had posterior fossa arachnoid cysts.

In a review of 63 patients with Apert syndrome prior to craniofacial surgery, Khong et al. Andreou et al. She also developed a low-grade papillary urothelial carcinoma of the bladder. No FGFR3 mutations were identified in the bladder tumor. Although most cases of Apert syndrome are sporadic, it also follows autosomal dominant inheritance. Roberts and Hall observed affected mother and daughter. Van den Bosch quoted by Blank, observed the typical deformity in mother and son, and Weech reported mother and daughter.

The evidence strongly suggests autosomal dominant inheritance. Paternal age effect is demonstrable. Allanson described 2 sisters with Apert syndrome, born to normal, unrelated parents. Germinal mosaicism was proposed. Rollnick described what is purportedly the first example of male transmission of Apert syndrome in affected father and daughter. Leonard et al.

Chang et al. Lomri et al. Histologic analysis revealed premature ossification, increased extent of subperiosteal bone formation, and alkaline phosphatase-positive preosteoblastic cells in Apert fetal calvaria compared with age-matched controls.

Preosteoblastic calvaria cells isolated from Apert syndrome infants and fetuses showed normal cell growth in basal conditions or in response to exogenous FGF2. In contrast, the number of alkaline phosphatase-positive calvaria cells was 4-fold higher than normal in mutant fetal calvaria cells with the most frequent Apert mutation, SW These and other results showed that Apert FGFR2 mutations lead to an increase in the number of precursor cells that enter the osteogenic pathway, leading ultimately to increased subperiosteal bone matrix formation and premature calvaria ossification during fetal development; thus, a connection was established between the altered genotype and the cellular phenotype in craniosynostosis of Apert syndrome.

Miraoui et al. The increased EGFR protein expression in Apert osteoblasts resulted in part from a posttranscriptional mechanism involving increased Sprouty2 -Cbl interaction, leading to Cbl sequestration and reduced EGFR ubiquitination. In all 40 unrelated patients with Apert syndrome, Wilkie et al. The findings confirmed that Apert syndrome is allelic to Crouzon syndrome.

In a patient with Apert syndrome, Oldridge et al. In a series of cases of Apert syndrome, Oldridge et al. Two patients had an Alu-element insertion in or near exon 9 Lajeunie et al. One affected fetus had the SF mutation. Moloney et al. Using sequence analysis of the neighboring introns flanking the mutation-prone exon and a novel PCR-based assay, ARMS amplification refractory mutation system , to determine the phase of the mutant allele and nearby polymorphisms in 57 informative families, Moloney et al.

The authors noted that a paternal bias for point mutations is evident in a number of disorders, but that the extreme skewing in favor of paternal mutations observed in Apert syndrome is unusual. A paternal age effect was noted. The data suggested a stronger paternal age effect for the SW mutation, which involves a CpG dinucleotide, than for the PR mutation, which does not. Glaser et al.

The number of sperm with FGFR2 mutations increased in the oldest age groups among men who did not have a child with Apert syndrome. These older men were also more likely to have both mutations in their sperm. However, this age-related increase in mutation frequency was not sufficient to explain the Apert syndrome birth frequency. In contrast, the mutation frequency observed in men who were younger and had children with Apert syndrome was significantly greater, suggesting selection for sperm with specific mutations.

No age-related increase in the frequency of these mutations was observed in leukocytes.


Apert syndrome

Apert syndrome is a genetic disorder characterized by skeletal abnormalities. A key feature of Apert syndrome is the premature closure of the bones of the skull craniosynostosis. This early fusion prevents the skull from growing normally and affects the shape of the head and face. In addition, a varied number of fingers and toes are fused together syndactyly. Craniosynostosis causes many of the characteristic facial features of Apert syndrome.


Sindrome di Apert

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Thought to occur from a defect on the fibroblast growth factor receptor 2 FGFR2 gene, located on chromosome 10q It can be inherited as an autosomal dominant trait, although most cases are thought to be sporadic. The differential includes other forms of acrocephalosyndactyly and acrocephalopolysyndactyly :. Please Note: You can also scroll through stacks with your mouse wheel or the keyboard arrow keys. Updating… Please wait. Unable to process the form. Check for errors and try again.


NCBI Bookshelf. Apert syndrome is characterized by the presence of multisuture craniosynostosis, midface retrusion, and syndactyly of the hands with fusion of the second through fourth nails. Almost all affected individuals have coronal craniosynostosis, and a majority also have involvement of the sagittal and lambdoid sutures. The midface in Apert syndrome is underdeveloped as well as retruded; a subset of affected individuals have cleft palate. The hand in Apert syndrome always includes fusion of the middle three digits; the thumb and fifth finger are sometimes also involved. Feeding issues, dental abnormalities, hearing loss, hyperhidrosis, and progressive synostosis of multiple bones skull, hands, feet, carpus, tarsus, and cervical vertebrae are also common.

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