Unilateral Coronal Craniosynostosis in an Apert-Like Patient

Abstract

Background and Significance:

Apert syndrome is a congenital disorder of patients who typically present with bilateral coronal craniosynostosis and varying degrees of complex syndactyly of the hands and feet, among other features. We describe a unique presentation of a rare Apert-like patient with unilateral coronal craniosynostosis and complex syndactyly of the hands and feet.

Case Report:

A 2-year-old male patient presented to the craniofacial clinic with his mother due to a concerning head shape. The patient also had bilateral syndactyly of the hands and feet and underwent prior surgical release of the third web space. Computerized tomography of the head illustrated a small open anterior fontanelle, a left harlequin orbit, complete left coronal craniosynostosis, and a patent right coronal suture. The patient subsequently underwent fronto-orbital advancement for expansion of the cranial vault and correction of the asymmetric forehead and orbit. The procedure resulted in improvement of his deformity.

Conclusion:

This case illustrates a unique presentation of an acrocephalosyndactyly (ACS) syndrome with asymmetric, unilateral coronal craniosynostosis and complete complex syndactyly of the hands and feet that is most consistent with Apert syndrome. Although the majority of patients with ACS can be categorized into known syndromes, other more unusual presentations must still be considered. Such unique cases are exceedingly rare and only through additional reporting and review of unique phenotypes can new subtypes of common ACS syndromes be classified.

Background

Apert syndrome is one syndrome within a group of congenital disorders referred to as acrocephalosyndactyly (ACS), along with Crouzon, Saethre-Chotzen, and Pfeiffer syndrome.¹ Although varying in their presentation and severity of findings, each is associated with craniosynostosis and, commonly, syndactyly of the hands and/or feet.^2-5 Apert syndrome (ACS type I) is typically characterized by bilateral coronal craniosynostosis, complex syndactyly of the hands and feet, and other craniofacial deformities.¹ These deformities include midface hypoplasia, flat occiput, brachycephaly, hypertelorism, and proptosis.⁶ Apert syndrome affects 1 in 65 000 to 160 000 live births and both genders equally.^7,8 It is associated with advanced paternal age and allelic mutations of the fibroblast growth factor receptor 2 (FGFR2).^8,9 These patients routinely require surgical correction of the hand and foot deformities, as well as expansion and remodeling of the cranial vault.¹⁰ Although Apert patients typically present with bicoronal craniosynostosis, confirmed cases of Apert syndrome without coronal craniosynostosis have been reported.^11,12 In this report, we describe the unique presentation of a rare Apert-like patient with unicoronal craniosynostosis.

Case Report

A 2-year-old male presented to the craniofacial clinic at the Department of Plastic and Reconstructive Surgery at the Johns Hopkins University Medical Center with his mother due to concern for abnormal head shape. He was born with forehead asymmetry that significantly worsened over the subsequent year. The patient also had syndactyly of the hands and feet and underwent prior surgical release of the hand. He was given a prepresentation diagnosis of Apert syndrome, although genetic testing was not performed at the patient’s home facility. The patient was said to have “frequent colds” and an otherwise normal development. No other abnormalities were found. The parents and other family members were clinically normal.

Initial evaluation revealed anterior plagiocephaly, downslanting palpebral fissures, midface hypoplasia, hypertelorism, and nasal root deviation (Figure 1). A Hertel exophthalmometer was not available at the time of initial presentation; however, based on exam and clinical photographs, the patient clearly exhibited bilateral proptosis that was mild. The patient also demonstrated bilaterally symmetrical and complete complex syndactyly of the index and middle digit and of the ring and small digit since birth. The thumbs were broad with only mild webbing of the first web space bilaterally. The patient underwent prior release of the third web space (Figure 2A). Both feet demonstrated complete complex syndactyly of the first through fourth digits with separate nails for all digits (Figure 2B). Computerized tomography (CT) images of the head revealed a small (1 cm) anterior fontanelle, left-sided harlequin orbital deformity, and complete left unicoronal craniosynostosis (Figure 3). Other CT findings included a retruded maxilla with relative Angle class III malocclusion.

Figure 1.

Frontal clinical view of the face. Marked asymmetry of the forehead and brows are shown. The left eyebrow is peaked due to fusion of the left coronal suture and an underlying harlequin orbit deformity. The nasal root is also seen deviated toward the patient’s left. The patient also exhibited mild bilateral proptosis.

Figure 2.

Complex complete syndactyly of bilateral hands and feet. The patient’s hand demonstrated complete complex syndactyly and digits 2 to 5 with broad thumbs. The right hand is shown after a prior surgical release of the third web space (A). Complete complex syndactyly of bilateral feet involved digits 1 to 4 (B).

Figure 3.

Three-dimensional reconstruction of a computed tomography scan of the head. Complete fusion of the left coronal suture with patency of the right coronal suture is demonstrated. A left harlequin orbit deformity and nasal root deviation to the left is also appreciated. This patient also demonstrated maxillary hypoplasia with relative Angle class III malocclusion.

After the family was counseled regarding the above findings, the patient underwent a fronto-orbital advancement for expansion of the cranial vault and correction of the asymmetric forehead and orbit. During surgery, the left unicoronal craniosynostosis was confirmed with a clearly identifiable right coronal suture (Figure 4). The brain and intracranial contents appeared normal. The patient’s craniofacial deformity improved postoperatively and there have been no clinical signs of increased intracranial pressure up through his last follow-up at 12 months postoperatively.

Figure 4.

Intraoperative view of the skull prior to fronto-orbital advancement. Asymmetry of the forehead with left frontal retrusion and right frontal bossing is demonstrated. A completely patent right coronal suture (black arrow) and synostosis of the left coronal suture is confirmed.

Discussion

This case report presents a unique patient with findings most consistent with Apert syndrome and a previously unreported unicoronal craniosynostosis. We analyzed this patient’s findings in detail, compared to other Apert patients. Such unique cases are exceedingly rare and only through reporting and reviewing unique phenotypes can new subtypes of common ACS syndromes be classified.

Acrocephalosyndactyly is a group of syndromes with the common findings of craniosynostosis and syndactyly. Acrocephalosyndactyly is also associated with varying degrees of developmental deficiency from normal intelligence to severe cognitive deficits.¹³ Craniosynostosis in these syndromes is typically bilateral and involves the coronal sutures in most cases. The severity of syndactyly varies from normal hands and feet in the majority of Crouzon patients to complete soft tissue and bony syndactyly in patients with Apert syndrome.¹⁴ This patient’s hands demonstrated fusion of digits 2 to 5, while the feet demonstrated fusion of digits 1 to 4. This patient’s complete, complex syndactyly of the hands can be classified as a type I Apert hand, which is the most common subtype.¹⁵ The feet are more consistent with a type II Apert deformity given the osseous fusion of the first digit to the second digit up until the distal phalanx, where there is a separate nail for each digit. A type III or “rosebud” hand was not observed in this patient. Craniofacial dysmorphologies in this patient consistent with Apert syndrome included brachycephaly, midface hypoplasia with relative Angle class III malocclusion, hypertelorism, bilateral proptosis, and bitemporal widening. Most Apert patients also include a midline defect from the glabella to the posterior fontanelle as well as proptosis.^13,16 At 2 years of age, this patient instead possessed a small open anterior fontanelle.

Our patient also demonstrated significant craniofacial asymmetry. The classically described Apert harlequin orbital deformity was only observed on this patient’s left side (on the side of the fused coronal suture). Additionally, the patient exhibited anterior plagiocephaly with right-sided frontal bossing and nasal root deviation toward the fused suture line. The characteristic appearances in Apert patients are mostly symmetrical due to bilateral coronal craniosynostosis, which is almost uniformly present at birth.¹⁷ Approximately one-third of patients in a large series of 136 Apert cases demonstrated cranial vault asymmetry secondary to megalencephaly, patency of other calvarial sutures, or synchondroses.¹⁸ In this patient, the patent right coronal suture likely contributed to the significant asymmetries observed. In addition to bicoronal craniosynostosis, many Apert infants also have premature fusion of the sagittal, metopic, and lambdoid sutures,^19,20 which this patient did not have.

Overall, unicoronal synostosis is uncommon with an incidence of only 1 in 10 000 live births.²¹ Most cases are sporadic and rarely syndromic. In comparison with other ACS syndromes, Crouzon, Saethre-Chotzen, and Pfeiffer syndromes, this patient has findings most similar to Apert syndrome. They can also be distinguished by a distinct combination of craniofacial and limb features. Crouzon syndrome (ACS type II) is characterized by bilateral coronal craniosynostosis, midfacial hypoplasia, but with normal digits or mild degree of syndactyly. Although bicoronal craniosynostosis is the definitive feature in both Apert and Crouzon syndrome, the craniofacial dysmorphologies demonstrate significant variation at all ages. It has been noted that turribrachycephaly is more severe in Apert syndrome, especially during infancy.²² Our patient’s presentation was relatively mild within the spectrum of Apert patients and was noted to involve anterior plagiocephaly present at birth, which continued to worsen until his presentation to our clinic at 2 years of age. This mild presentation was likely due to having unicoronal craniosynostosis with no other suture synostosis. Overall, the craniofacial features in this patient and the degree of syndactyly are most consistent with Apert syndrome.

Saethre-Chotzen syndrome (ACS type III) is characterized by craniosynostosis involving unilateral or bilateral coronal sutures of variable severity and is caused by a mutation of the TWIST1 gene.²³ In addition, Saethre-Chotzen syndrome presents with a characteristic ear deformity consisting of small pinna with a prominent crus, which this patient did not have. When present, mild and incomplete syndactyly typically involves soft tissue of the index and middle digits. Pfeiffer syndrome (ACS type V) presents with varying degrees of craniofacial deformities from mild turribrachycephaly with relatively normal neurological functions to classic cloverleaf deformity with severe mental deficiencies.² In addition, maxillary hypoplasia and brachydactyly with broad thumbs are typical findings. When present, mild and incomplete syndactyl involves soft tissue only. Despite having broad thumbs, our patient exhibited complete complex syndactyly of 4 digits in the hands and feet, which is not consistent with either Saethre-Chotzen or Pfeiffer syndrome.

With regard to genetics, a specific mutation in this patient’s genome was not documented because the family declined testing. Both parents were clinically normal and could not recall another family member with a craniofacial anomaly. Apert syndrome is associated with point mutations of the FGFR2 gene.⁹ Most of Apert cases are sporadic, but an autosomal dominant pattern is demonstrated when the syndrome is inherited. Two specific missense mutations have been reported in nearly 99% of Apert cases: S252W and P253R.²⁴ Although syndactyly has been described as more severe in patients with a P253R mutation, postoperative craniofacial features following cranial vault reconstruction have been noted to be comparatively better than in patients with an S252W mutation.²⁵ In contrast, cleft palate is more common in patients with an S252W mutation.²⁶

Unique cases of ACS have been reported in addition to common presentations of the known ACS syndromes. Pfeiffer described a patient with unilateral coronal craniosynostosis, mild syndactyly, and jejuna atresia.²⁷ Few, rare syndromic cases of unicoronal craniosynostosis have been described with Saethre-Chotzen syndrome.²⁸ Two cases of Apert syndrome with bilateral patent coronal sutures have also been reported.^11,12 Apert syndrome without bilateral coronal synostosis is exceptionally rare. Only one previously published case report of an Apert patient with unicoronal synostosis was found.²⁹ Their case also shared several other features similar to our patient including anterior plagiocephaly and Apert type I hand deformities.^30,31 Genetic analysis was able to be performed in their case, which lacked the specific missense mutations of the FGFR2 gene that is associated with most Apert patients. Therefore, further study is warranted to determine the specific genomic anomaly that may lead to this rare presentation. This report contributes to the sparse literature on unique presentations of ACS syndromes.

Conclusion

The constellation of craniofacial findings and complete complex syndactyly of the hands and feet in this patient is most consistent with Apert syndrome. However, this patient’s synostosis of only a unilateral coronal suture, degree of craniofacial asymmetry, with relatively mild overall presentation make this case unique within the spectrum of ACS syndromes. Unfortunately, genetic testing was declined to confirm the patient’s diagnosis. Although the majority of patients with ACS can be categorized into known syndromes, other more unusual presentations must still be considered. Such unique cases are exceedingly rare and only through additional reporting and review of unique phenotypes can new subtypes of common ACS syndromes be classified.