Agenesis or premature closure of the cranial sutures, midface hypoplasia, and symmetrical syndactyly of hands and feet involving at least the second, third, and fourth digits. Partial cervical spinal fusion is common. Numerous facial anomalies are seen. Heart defects may be present.
The first two cases were reported in 1894 by S.W. Wheaton and then more extensively described in 1906 by the French pediatrician Eugène Charles Apert (1868–1940).
1:65,000 to 1:160,000 live births. Both sexes are equally affected.
Autosomal dominant inheritance has been reported; however, the majority of cases appears to be sporadic resulting from new mutations in the gene encoding fibroblast growth factor receptor 2 (FGFR-2), which has been mapped to chromosome 10q26.
The defect results in abnormal osseous development with irregular bridging of the mesenchymal tissue that eventually forms bone. The cranium and distal extremities are predominantly affected.
Based on the clinical findings and radiographic examinations confirming the osseous abnormalities.
The coronal sutures are most commonly involved, resulting in acrobrachycephaly with a high forehead and flat facies. The skull base shows decreased total anteroposterior dimensions with affecting the anterior, middle, and posterior cranial fossae. Prominent convolutional markings along the skull inner table are found in more than half of the patients and may reflect either a generalized disturbance of normal brain development or a normal consequence of rapid brain growth in a constrained environment and a still malleable cranium. The level of mental retardation is variable and, while some studies found a correlation with brain malformations, others did not. Nonprogressive ventriculomegaly is the most common central nervous system anomaly found in approximately half the patients; however, hydrocephalus with increased intracranial pressure (ICP) has also been described. Arnold-Chiari malformation Type I or crowding of the foramen magnum, agenesis of the corpus callosum and the septum pellucidum, encephaloceles, and anomalies of the limbic system and the pyramidal tract have all been described. Fused cervical vertebrae were found in up to two-thirds of patients and most commonly involved C5 and C6, with single fusion being slightly more common than multiple fusions. Some experts consider the fusions to be progressive, ie, they can be absent at a young age and develop later on in life. Facial dysmorphism commonly includes a horizontal groove above the supraorbital ridge and a break in the continuity of eyebrows. Further facial findings are shallow orbits, spheno-ethmoido-maxillary (midface) hypoplasia, with a narrow and high-arched palate (with cleft palate in approximately 30%) and a prominent mandible. The nose is short with a depressed nasal bridge and bulbous tip. Choanal stenosis or ...