- Email: [email protected]
Apert syndrome: a case report and discussion
ELS EVI E R
Clinical Eye and Vision Care 11 (1999) 215-220
www.elsevier.com/locate/clineyeviscare
Case report
Apert syndrome: a case report and discussion Melissa J. Melott, O.D.” Castle Creek
5875 Castle Creek Parkway N, Suite 136, Indianapolis, IN 46250, USA Accepted 9 August 1999
Abstract
Apert syndrome is a rare genetic disorder characterized by cranial suture malformations, ocular abnormalities, and syndactyly. Some of the ocular manifestations include proptosis, downward slant of the lateral canthi with a corresponding S-shaped ptosis, strabismus, hypertelorism, and optic atrophy. As appropriate treatment may significantly alter the structural and functional capacity of these patients, it is important to understand the fundamental systemic and ocular features of the disorder. The clinical course of an elderly woman who suffers from systemic and ocular complications of Apert syndrome is presented. 0 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Craniosynostosis; Apert syndrome; Cranial suture; Syndactyly; Hyperacrobracycephaly
1. Introduction
Apert syndrome is a complex disorder characterized by craniosynostosis, midface hypoplasia, ocular abnormalities, and syndactyly. The frequency of Apert syndrome is 1 in 100000 in the general population [l]. Most cases of Apert syndrome are sporadic in inheritance, although both autosomal dominant and autosoma1 recessive transmission have been documented [2,3]. The syndrome affects males and females equally and has been noted in Caucasian, African-American and Asian races [2]. Several theories exist for the syndrome’s pathogenesis, however, the true mechanism remains unknown [2,4]. Premature fusion of the calvarial sutures results in abnormal head shape, altering the structure and function of the orbit, maxillary, and cranial base regions [4]. Due to the alteration in orbital development, Apert patients often present with visual and
* Tel.: + 1-317-845-2020;fax: + 1-317-570-2254.
ophthalmic disturbances. The primary eye care provider should be aware of the features of the disorder and the potential visual disturbances related to the syndrome. 2. Case report
2.1. Medical history
An 83-year-old Caucasian female presented for an eye examination with the complaint of a gradual decrease in distance and near vision occurring over the last few years. She also noted that her upper and lower eyelids ‘drooped’ and her eyes ‘dripped water’ constantly. She stated that this condition seemed to be worsening daily. The patient had a history of osteoarthritis, chronic dyspepsia, anemia, and hypertension. She was currently taking lisinopril 20 mg, niferex 150 mg, famotidine 20 mg, chlorophyll 3 mg, and acetaminophen daily. There was no family history of eye disease or history of intravenous drug use.
0953-4431/99/$ - see front matter 0 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 9 5 3 - 4 4 3 1( 9 9 ) 0 0 0 3 8 - 7
216
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
2.2. Physical examination Unaided distance visual acuity measured 20/300 O.D. and 20/400 O.S. with no improvement through
manifest refraction. Confrontation visual fields and pupils were unremarkable. A V-shaped pattern of motility was observed with five prism diopters exotropia in upgaze, orthophoria in primary gaze, and 25 prism diopters esotropia in downgaze. Keratometry
Fig. 1. Ocular manifestations of Apert Syndrome. Note the ectropion, proptosis, and downward slanting of the canthi. Fig. 2. Classic Apert appearance. Note the midface deficiency, depressed nasal bridge, and steep forehead. Fig. 3. Hands of a patient with Apert syndrome. Fig. 4. Status post-operative lid procedures. Note the proper alignment of lids to the globe. Also note redness of right eye with corneal complications.
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
readings were 42.00 @ 180/42.00 @ 090 O.D. and 42.00 @ 180/44.00 @ 090 O.S. with clear and regular mires. Tensions by applanation were 15 mmHg O.D. and 18 mmHg O.S. at 14.30 h. Hertel exophthalmometry readings were 24 mm O.D. and O.S. with a base of 110 mm. Interpupillary distance was 75 mm. Biomicroscopy revealed a mild S-shaped ptosis of the upper eyelids and a downward slant to the lateral canthi. There was cicatricial ectropion of the lower lids with secondary punctal eversion, stenosis, and epiphoria (see Fig. 1). A resultant moderate punctate epithelial keratitis was present O.U. There was scarring and neovascularization of the temporal cornea in the right eye secondary to exposure. The anterior chamber and iris were unremarkable with negative transillumination defects noted. The lenses had dense nuclear sclerosis O.U. A dilated examination was attempted, however, the fundi were not discernible through the ocular media. The facial features noted included a recessed maxillary region, a depressed nasal bridge, and a long steep forehead (see Fig. 2). Symmetrical syndactyly of the hands occurred with the fusion including all five digits (see Fig. 3). The patient also had symmetrical syndactyly of the feet. The patient was alert and oriented to person, place, and time. The patient was placed on a regimen of ocular lubrication (Refresh Tears), administered every other hour while awake. Approximately 1 month later, she underwent cataract extraction by phacoemulsification with posterior chamber lens implantation in the right eye. At the 1-day postoperative visit, pinhole visual acuity was 20/40 O.D. Slit lamp examination revealed a secure conjunctivally-based wound, a deep anterior chamber with grade one cells, and a well-positioned posterior chamber intraocular lens. The cornea had mild superficial punctate keratitis and mild stromal edema. Left eye testing was unchanged from the previous exam. The patient was instructed on the use of postoperative anti-inflammatory drops (Tobradex q.i.d.1 and was asked to continue on the same ocular lubrication therapy (Refresh Tears).
Fig. 5. Five main cranial sutures of the skull.
217
Approximately 1 month later, the patient had a full thickness skin graft to repair the ectropion of the left lower lid. Skin from the left upper eyelid was used to correct the lid abnormality of the lower lid. Canaliculoplasty and Crawford tube placement were performed in both eyes to correct the punctal stenosis and epiphoria. In order to prevent further desiccation of the right eye until the complete skin graft procedure could be completed, a partial tarsorrophy of the right lateral canthus was also performed. The skin graft was completed 1 month later without complications. As in the left eye, skin from the right upper lid was used to correct the lower lid ectropion. The results of these procedures were deemed successful, as there was negative ectropion and minimal exposure keratitis O.U. The patient had mild incomplete lid closure in the right eye. The patient returned to the clinic 1 month later stating that her vision was improved and both eyes were feeling much better until approximately 1 week prior. At that time, she stated that her right eye began to burn, water, secrete mild mucus discharge, and was causing a significant amount of pain. She denied symptoms in the left eye. Best corrected visual acuity was 20/200 O.D. and Count Fingers at 5 feet O.S. Biomicroscopy of the right eye revealed negative ectropion and punctal stenosis. There was incomplete closure of the right upper and lower eyelids resulting in significant superficial punctate keratitis with epiphora and moderate conjunctival injection. There were mild collarettes and debris in the lashes. There was a secure wound, a deep and quiet anterior chamber, and a well-positioned posterior chamber intraocular lens with a clear capsule. Biomicroscopy in the left eye revealed aligned lids with negative ectropion, stenosis, or epiphora (see Fig. 4). There was a clear cornea, a deep and quiet anterior chamber and a grade 4 cataract. The patient was started on antibiotic ointment O.D. (Bacitracin b.i.d.1 and lubrication O.U. (Refresh Tears). The patient was asked to return to the clinic immediately if symptoms worsened or in 1 week if the symptoms persisted. She was instructed to discontinue the Bacitracin in 1 week and to continue her lubrication therapy. At the 6-month follow-up visit, the patient stated that her eyes were feeling fine with her only symptoms relating to the cataract in the left eye. She stated that the right eye had several episodes of redness, burning, tearing, and pain since her last visit. She stated that these episodes resolved with time and lubricating drops. Best corrected visual acuity was 20/400 O.D. and Count Fingers at 3 feet O.S. Biomicroscopy of the right eye revealed negative ectropion and punctal stenosis. There was incomplete lid closure resulting in corneal exposure keratitis, a central epithelial erosive area and moderate neovasculariza-
218
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
tion (see Fig. 4). There was a secure wound, a deep and quiet anterior chamber, and a well-positioned posterior chamber intraocular lens. Fundus evaluation was grossly normal. (Evaluation was very difficult due to patient’s light sensitivity.) Biomicroscopy of the left eye revealed a clear cornea, a deep and quiet anterior chamber, and grade 4 nuclear sclerosis of the lens. No view of the fundus was obtained due to the ocular media. The patient was placed on antibiotic drops O.D. (Ciloxan q.i.d.1, lubricating drops O.U. (Refresh Tears every 2-3 h), and lubricating ointment O.U. (Lacrilube QHS). She returned in 1 week with complete resolution of the epithelial staining, however, an area of negative stain remained. The antibiotic drops were discontinued, however, she was asked to continue on the lubrication regimen. She has been scheduled for a reshape of the lid to help with the incomplete closure. She was also scheduled for cataract extraction with posterior chamber lens implantation in the left eye. The patient underwent cataract extraction by phacoemulsification with posterior chamber lens implantation in the left eye. At the 1-day postoperative visit, pinhole visual acuity was 20/100 O.D. and 20/200 O.S. Biomicroscopy of the left eye revealed grade 2 corneal edema, a secure conjunctivally-based wound, and a deep anterior chamber with grade 1 cells. One week later, the patient returned for follow-up and best corrected visual acuity was 20/200 O.D. and 20/50 O.S. Biomicroscopy of the right eye revealed corneal neovascularization, mild exposure keratitis, and a deep and quiet anterior chamber. Biomicrosopy of the left eye revealed a clear cornea, a deep anterior chamber with mild cells, and a well-positioned posterior chamber intraocular lens. The patient was scheduled to return for an internal tarsorrophy in the right eye but has deferred the procedure at the present time. This patient underwent several successful treatment procedures to enhance vision and alleviate symptoms. The right eye needs further enhancement to completely resolve the patient’s symptoms and maximize visual acuity. As this treatment continues to be deferred, the patient is at risk of further corneal scarring, neovascularization, and erosion. There is also a significant risk for perforation if left untreated for a long period of time.
3. Discussion
3.1. Normal development Normal development of the cranial sutures is vital
Table 1 Suture
Closure begins in years
Metopic Sagittal Coronal Lamboidal Squamosal
2 22 24 26 35
to the structure and function of the skull and related soft tissue. Five major sutures are present in the skull: coronal, lamboidal, sagittal, squamosal and metopic [2,5] (see Fig. 5). Sutures are areas of adaptation that constantly respond to changes in soft tissue growth of the brain and related structures. As the brain develops, there is an increase in intracranial pressure which results in sutural gap widening. A layer of osteoid tissue is deposited in the growth area which eventually mineralizes to bone. This process is replicated until all growth and development is completed. At this point, adaptation is no longer needed and osteoid is deposited over the entire sutural gap to result in a complete bony structure [2,6]. The normal timeline of sutural closure is shown in Table 1.
3.2. Cruniosynostosis Several genetic disorders result in craniosynostosis, the process of premature fusion of the sutures of the skull during development. Premature synostosis occurs when osteoid is deposited over the entire sutural opening before the developmental process is complete 121. This results in malformations of the skull, face, brain, and other related soft tissue structures. Due to premature bone development, no growth is allowed along the closed suture line. Compensatory growth occurs along the unfused sutures [2]. Premature synostosis can affect one or more sutures resulting in various skull configurations and thus many different named syndromes. In Apert syndrome, the most common suture which is obliterated early is the coronal suture and therefore a hyperacrobracycephaly skull configuration is produced [2]. Hyperacrobracycephaly describes the abnormal shortening of the anteroposterior diameter of the skull with a compensatory increase in the vertical skull development. In the Apert syndrome population, the metopic suture is also affected by remaining open for a longer period of time than normal [2,4]. The combination of the two affected sutures result in a steep, long forehead with a protruding bregma. Crouzons syndrome is similar to Apert syndrome in that there is a premature fusion of the coronal suture as well. The only clinical difference
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
in the syndromes is the absence of syndactyly in Crouzons syndrome. 3.3. Systemic characteristics 3.3.1. Facial features Due to early suture closure in Apert patients, the maxillary bone is underdeveloped. This results in recession of the midfacial region and a mandibular prognathic appearance [2,6]. The nasal bridge is depressed and the cartilage of the nose is humped and beaked. 3.3.2. Ears Apert patients often have low set ears resulting in Eustachian tube malformations [2]. Therefore, the possibility of significant hearing deficits should be considered in Apert syndrome patients. 3.3.3. Mouth As a result of premature suture fusion, the maxillary region is deformed. The palate is highly arched resulting in a V-shaped dental configuration [6]. Therefore, these individuals have severely crowded teeth and bulging alveolar ridges [6]. 3.3.4. Mental Both mental deficiency and normal intelligence have been reported in Apert syndrome [2]. The true percentage of mental retardation remains unknown. 3.3.5. Digits Syndactyly of the digits of both hands and feet are a characteristic of Apert syndrome. Digits 2, 3, and 4 are the most commonly fused joints [2,5,71. The first and the fifth digits may be joined to the rest or may be separate and the nails may be joined completely or only partially continuous [2]. 3.3.6. Spine Progressive calcification of the cervical region of the spine occurs with age [2]. 3.3.7. Cardiovascular In Cohen’s series of 55 Apert syndrome patients, 9% had cardiovascular defects of various kinds [2]. No specific cardiovascular defect has been identified in Apert syndrome. 3.4. Ophthalmic manifestations 3.4.1. Proptosis / exophthalmos The proptosis occurring in Apert syndrome is pri-
219
marily related to the reduced volume of the bony orbital space. The decrease in the development of the maxilla results in a decrease in the size of the orbital floor. Proptosis also appears to be more prominent due to the midfacial hypoplasia of these patients [2,8]. 3.4.2. Lids /palpebral fissure The characteristic lid appearance in Apert syndrome is a horizontal downward displacement of the lateral canthi with a corresponding S-shaped upper lid configuration [l]. This results in lid laxities and malformations such as ectropion and entropion. 3.4.3. Interpupilla y distance In Apert patients, there is an increase in the distance between the medial walls of the orbits which is termed orbital hypertelorism [8].The distance between the lateral canthal walls, described clinically as interpupillary distance, is also secondarily increased in these patients. 3.4.4. Cornea The most common corneal manifestation is a chronic superficial punctate keratitis secondary to exposure [2]. The abnormal lid configuration and proptosis decreases the coverage of the eye and results in severe drying of corneal and conjunctival surfaces. If lubricants are not used, there can be severe ulceration, scarring, and vascularization. Keratoconus has also been described in Apert syndrome but a statistical analysis has not been done to determine if these patients are at a higher risk for the disorder [8]. 3.4.5. Ocular motility Strabismus is a common occurrence in Apert syndrome. The most frequent type of misalignment is exotropia [2,8]. A V-pattern of motility is also very common, with exotropia in upgaze, orthophoria in primary gaze, and esotropia in downgaze [2]. Several theories exist for the mechanism of strabismus in these patients. A likely explanation suggests that the decrease in orbital space with the compression of the soft tissue structures results in strabismus. 3.4.6. Optic nerve An increase in intracranial pressure often precedes the premature closure of cranial sutures. If this pressure remains high for a significant amount of time, papilledema can occur, potentially leading to optic atrophy [8]. Researchers disagree about the etiology of the optic atrophy that is seen in craniosynostosis patients. Some feel that in order to have optic atrophy one must have had increased intracranial pressure at
220
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
some time during their life. Others believe that it is not necessary to have had an episode of papilledema to have optic atrophy [2].
3.4.7. Retinal vascularity There is an increased frequency of retinal vascular tortuosity in Apert patients. Some authors believe that the tortuosity is evidence of previous papilledema 121. 3.4.8. Repactive error Some theories have suggested that hyperopia would be more common in Apert patients. However, one must consider not only the shallow orbit but also the lid configuration and corneal curvature when analyzing potential refractive errors in these patients. With all these considerations, hyperopia and myopia have been found to be of similar incidence in Apert syndrome [2]. 4. Management
The initial treatment for craniosynostosis is a cranio-orbital decompression surgical procedure. This procedure has the highest success rate if performed before the age of 11 months [1,2]. The surgical procedure actually releases the prematurely fused sutures of the skull. If the operation is performed at an early stage as suggested, normal development can proceed [2]. Careful follow-up of the patient is necessary, including regular eye examinations. Any signs of increased intracranial pressure would signify the need for a repeat of the decompression procedure. If the
Apert patient does not undergo a surgical procedure at an early age, the benefits of the procedure are minimized [1,2,6]. 5. Summary
Apert syndrome is a rare disorder involving craniosynostosis, ocular abnormalities and syndactyly. Ocular abnormalities in Apert syndrome results from the malformation of surrounding bony orbits. The ocular pathology of craniosynotosis is potentially threatening to the visual function of these patients. Vision loss is often preventable if it is recognized and treated appropriately. References 111 Posnick J. The craniofacial dysosotosis syndromes, staging of reconstruction and management of secondary deformities. Clin Plast Surg 1997;24(3):429-433. 121 Cohen Jr. MM. Craniosynostosis: diagnosis, evaluation, and management. New York: Raven Press, 1986:227-243. 131 Fatt HV, Griffin JR, Lyle WM. Genetics for primary eye care practitioners. 2nd ed. Boston: Butterworth-Heinemann, 1992:118-136. 141 Cohen MM Jr, Kreiborg S. Unusual cranial aspects of Apert syndrome. J Craniofac Genet Dev Biol 1994;14:48-56. 151 Agur AMR, Lee M. Grant’s atlas of anatomy. 9th ed. Baltimore: Williams & Williams, 1991. 161 Kreigborg S, Cohen Jr. MM. The oral manifestations of Apert syndrome. J Craniofac Genet Dev Biol 1992;1241-48. 171 Anderson PJ, Hall CM, Evans RD, Jones BM, Hayward RD. The feet in Crouzons syndrome. J Craniofac Genet Dev Biol 1997;17:43-47. 181 Paven-Langston MD. Manual of ocular diagnosis and therapy. 3rd ed. Boston: Little, Brown and Company.
Clinical Eye and Vision Care 11 (1999) 215-220
www.elsevier.com/locate/clineyeviscare
Case report
Apert syndrome: a case report and discussion Melissa J. Melott, O.D.” Castle Creek
5875 Castle Creek Parkway N, Suite 136, Indianapolis, IN 46250, USA Accepted 9 August 1999
Abstract
Apert syndrome is a rare genetic disorder characterized by cranial suture malformations, ocular abnormalities, and syndactyly. Some of the ocular manifestations include proptosis, downward slant of the lateral canthi with a corresponding S-shaped ptosis, strabismus, hypertelorism, and optic atrophy. As appropriate treatment may significantly alter the structural and functional capacity of these patients, it is important to understand the fundamental systemic and ocular features of the disorder. The clinical course of an elderly woman who suffers from systemic and ocular complications of Apert syndrome is presented. 0 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Craniosynostosis; Apert syndrome; Cranial suture; Syndactyly; Hyperacrobracycephaly
1. Introduction
Apert syndrome is a complex disorder characterized by craniosynostosis, midface hypoplasia, ocular abnormalities, and syndactyly. The frequency of Apert syndrome is 1 in 100000 in the general population [l]. Most cases of Apert syndrome are sporadic in inheritance, although both autosomal dominant and autosoma1 recessive transmission have been documented [2,3]. The syndrome affects males and females equally and has been noted in Caucasian, African-American and Asian races [2]. Several theories exist for the syndrome’s pathogenesis, however, the true mechanism remains unknown [2,4]. Premature fusion of the calvarial sutures results in abnormal head shape, altering the structure and function of the orbit, maxillary, and cranial base regions [4]. Due to the alteration in orbital development, Apert patients often present with visual and
* Tel.: + 1-317-845-2020;fax: + 1-317-570-2254.
ophthalmic disturbances. The primary eye care provider should be aware of the features of the disorder and the potential visual disturbances related to the syndrome. 2. Case report
2.1. Medical history
An 83-year-old Caucasian female presented for an eye examination with the complaint of a gradual decrease in distance and near vision occurring over the last few years. She also noted that her upper and lower eyelids ‘drooped’ and her eyes ‘dripped water’ constantly. She stated that this condition seemed to be worsening daily. The patient had a history of osteoarthritis, chronic dyspepsia, anemia, and hypertension. She was currently taking lisinopril 20 mg, niferex 150 mg, famotidine 20 mg, chlorophyll 3 mg, and acetaminophen daily. There was no family history of eye disease or history of intravenous drug use.
0953-4431/99/$ - see front matter 0 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 9 5 3 - 4 4 3 1( 9 9 ) 0 0 0 3 8 - 7
216
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
2.2. Physical examination Unaided distance visual acuity measured 20/300 O.D. and 20/400 O.S. with no improvement through
manifest refraction. Confrontation visual fields and pupils were unremarkable. A V-shaped pattern of motility was observed with five prism diopters exotropia in upgaze, orthophoria in primary gaze, and 25 prism diopters esotropia in downgaze. Keratometry
Fig. 1. Ocular manifestations of Apert Syndrome. Note the ectropion, proptosis, and downward slanting of the canthi. Fig. 2. Classic Apert appearance. Note the midface deficiency, depressed nasal bridge, and steep forehead. Fig. 3. Hands of a patient with Apert syndrome. Fig. 4. Status post-operative lid procedures. Note the proper alignment of lids to the globe. Also note redness of right eye with corneal complications.
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
readings were 42.00 @ 180/42.00 @ 090 O.D. and 42.00 @ 180/44.00 @ 090 O.S. with clear and regular mires. Tensions by applanation were 15 mmHg O.D. and 18 mmHg O.S. at 14.30 h. Hertel exophthalmometry readings were 24 mm O.D. and O.S. with a base of 110 mm. Interpupillary distance was 75 mm. Biomicroscopy revealed a mild S-shaped ptosis of the upper eyelids and a downward slant to the lateral canthi. There was cicatricial ectropion of the lower lids with secondary punctal eversion, stenosis, and epiphoria (see Fig. 1). A resultant moderate punctate epithelial keratitis was present O.U. There was scarring and neovascularization of the temporal cornea in the right eye secondary to exposure. The anterior chamber and iris were unremarkable with negative transillumination defects noted. The lenses had dense nuclear sclerosis O.U. A dilated examination was attempted, however, the fundi were not discernible through the ocular media. The facial features noted included a recessed maxillary region, a depressed nasal bridge, and a long steep forehead (see Fig. 2). Symmetrical syndactyly of the hands occurred with the fusion including all five digits (see Fig. 3). The patient also had symmetrical syndactyly of the feet. The patient was alert and oriented to person, place, and time. The patient was placed on a regimen of ocular lubrication (Refresh Tears), administered every other hour while awake. Approximately 1 month later, she underwent cataract extraction by phacoemulsification with posterior chamber lens implantation in the right eye. At the 1-day postoperative visit, pinhole visual acuity was 20/40 O.D. Slit lamp examination revealed a secure conjunctivally-based wound, a deep anterior chamber with grade one cells, and a well-positioned posterior chamber intraocular lens. The cornea had mild superficial punctate keratitis and mild stromal edema. Left eye testing was unchanged from the previous exam. The patient was instructed on the use of postoperative anti-inflammatory drops (Tobradex q.i.d.1 and was asked to continue on the same ocular lubrication therapy (Refresh Tears).
Fig. 5. Five main cranial sutures of the skull.
217
Approximately 1 month later, the patient had a full thickness skin graft to repair the ectropion of the left lower lid. Skin from the left upper eyelid was used to correct the lid abnormality of the lower lid. Canaliculoplasty and Crawford tube placement were performed in both eyes to correct the punctal stenosis and epiphoria. In order to prevent further desiccation of the right eye until the complete skin graft procedure could be completed, a partial tarsorrophy of the right lateral canthus was also performed. The skin graft was completed 1 month later without complications. As in the left eye, skin from the right upper lid was used to correct the lower lid ectropion. The results of these procedures were deemed successful, as there was negative ectropion and minimal exposure keratitis O.U. The patient had mild incomplete lid closure in the right eye. The patient returned to the clinic 1 month later stating that her vision was improved and both eyes were feeling much better until approximately 1 week prior. At that time, she stated that her right eye began to burn, water, secrete mild mucus discharge, and was causing a significant amount of pain. She denied symptoms in the left eye. Best corrected visual acuity was 20/200 O.D. and Count Fingers at 5 feet O.S. Biomicroscopy of the right eye revealed negative ectropion and punctal stenosis. There was incomplete closure of the right upper and lower eyelids resulting in significant superficial punctate keratitis with epiphora and moderate conjunctival injection. There were mild collarettes and debris in the lashes. There was a secure wound, a deep and quiet anterior chamber, and a well-positioned posterior chamber intraocular lens with a clear capsule. Biomicroscopy in the left eye revealed aligned lids with negative ectropion, stenosis, or epiphora (see Fig. 4). There was a clear cornea, a deep and quiet anterior chamber and a grade 4 cataract. The patient was started on antibiotic ointment O.D. (Bacitracin b.i.d.1 and lubrication O.U. (Refresh Tears). The patient was asked to return to the clinic immediately if symptoms worsened or in 1 week if the symptoms persisted. She was instructed to discontinue the Bacitracin in 1 week and to continue her lubrication therapy. At the 6-month follow-up visit, the patient stated that her eyes were feeling fine with her only symptoms relating to the cataract in the left eye. She stated that the right eye had several episodes of redness, burning, tearing, and pain since her last visit. She stated that these episodes resolved with time and lubricating drops. Best corrected visual acuity was 20/400 O.D. and Count Fingers at 3 feet O.S. Biomicroscopy of the right eye revealed negative ectropion and punctal stenosis. There was incomplete lid closure resulting in corneal exposure keratitis, a central epithelial erosive area and moderate neovasculariza-
218
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
tion (see Fig. 4). There was a secure wound, a deep and quiet anterior chamber, and a well-positioned posterior chamber intraocular lens. Fundus evaluation was grossly normal. (Evaluation was very difficult due to patient’s light sensitivity.) Biomicroscopy of the left eye revealed a clear cornea, a deep and quiet anterior chamber, and grade 4 nuclear sclerosis of the lens. No view of the fundus was obtained due to the ocular media. The patient was placed on antibiotic drops O.D. (Ciloxan q.i.d.1, lubricating drops O.U. (Refresh Tears every 2-3 h), and lubricating ointment O.U. (Lacrilube QHS). She returned in 1 week with complete resolution of the epithelial staining, however, an area of negative stain remained. The antibiotic drops were discontinued, however, she was asked to continue on the lubrication regimen. She has been scheduled for a reshape of the lid to help with the incomplete closure. She was also scheduled for cataract extraction with posterior chamber lens implantation in the left eye. The patient underwent cataract extraction by phacoemulsification with posterior chamber lens implantation in the left eye. At the 1-day postoperative visit, pinhole visual acuity was 20/100 O.D. and 20/200 O.S. Biomicroscopy of the left eye revealed grade 2 corneal edema, a secure conjunctivally-based wound, and a deep anterior chamber with grade 1 cells. One week later, the patient returned for follow-up and best corrected visual acuity was 20/200 O.D. and 20/50 O.S. Biomicroscopy of the right eye revealed corneal neovascularization, mild exposure keratitis, and a deep and quiet anterior chamber. Biomicrosopy of the left eye revealed a clear cornea, a deep anterior chamber with mild cells, and a well-positioned posterior chamber intraocular lens. The patient was scheduled to return for an internal tarsorrophy in the right eye but has deferred the procedure at the present time. This patient underwent several successful treatment procedures to enhance vision and alleviate symptoms. The right eye needs further enhancement to completely resolve the patient’s symptoms and maximize visual acuity. As this treatment continues to be deferred, the patient is at risk of further corneal scarring, neovascularization, and erosion. There is also a significant risk for perforation if left untreated for a long period of time.
3. Discussion
3.1. Normal development Normal development of the cranial sutures is vital
Table 1 Suture
Closure begins in years
Metopic Sagittal Coronal Lamboidal Squamosal
2 22 24 26 35
to the structure and function of the skull and related soft tissue. Five major sutures are present in the skull: coronal, lamboidal, sagittal, squamosal and metopic [2,5] (see Fig. 5). Sutures are areas of adaptation that constantly respond to changes in soft tissue growth of the brain and related structures. As the brain develops, there is an increase in intracranial pressure which results in sutural gap widening. A layer of osteoid tissue is deposited in the growth area which eventually mineralizes to bone. This process is replicated until all growth and development is completed. At this point, adaptation is no longer needed and osteoid is deposited over the entire sutural gap to result in a complete bony structure [2,6]. The normal timeline of sutural closure is shown in Table 1.
3.2. Cruniosynostosis Several genetic disorders result in craniosynostosis, the process of premature fusion of the sutures of the skull during development. Premature synostosis occurs when osteoid is deposited over the entire sutural opening before the developmental process is complete 121. This results in malformations of the skull, face, brain, and other related soft tissue structures. Due to premature bone development, no growth is allowed along the closed suture line. Compensatory growth occurs along the unfused sutures [2]. Premature synostosis can affect one or more sutures resulting in various skull configurations and thus many different named syndromes. In Apert syndrome, the most common suture which is obliterated early is the coronal suture and therefore a hyperacrobracycephaly skull configuration is produced [2]. Hyperacrobracycephaly describes the abnormal shortening of the anteroposterior diameter of the skull with a compensatory increase in the vertical skull development. In the Apert syndrome population, the metopic suture is also affected by remaining open for a longer period of time than normal [2,4]. The combination of the two affected sutures result in a steep, long forehead with a protruding bregma. Crouzons syndrome is similar to Apert syndrome in that there is a premature fusion of the coronal suture as well. The only clinical difference
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
in the syndromes is the absence of syndactyly in Crouzons syndrome. 3.3. Systemic characteristics 3.3.1. Facial features Due to early suture closure in Apert patients, the maxillary bone is underdeveloped. This results in recession of the midfacial region and a mandibular prognathic appearance [2,6]. The nasal bridge is depressed and the cartilage of the nose is humped and beaked. 3.3.2. Ears Apert patients often have low set ears resulting in Eustachian tube malformations [2]. Therefore, the possibility of significant hearing deficits should be considered in Apert syndrome patients. 3.3.3. Mouth As a result of premature suture fusion, the maxillary region is deformed. The palate is highly arched resulting in a V-shaped dental configuration [6]. Therefore, these individuals have severely crowded teeth and bulging alveolar ridges [6]. 3.3.4. Mental Both mental deficiency and normal intelligence have been reported in Apert syndrome [2]. The true percentage of mental retardation remains unknown. 3.3.5. Digits Syndactyly of the digits of both hands and feet are a characteristic of Apert syndrome. Digits 2, 3, and 4 are the most commonly fused joints [2,5,71. The first and the fifth digits may be joined to the rest or may be separate and the nails may be joined completely or only partially continuous [2]. 3.3.6. Spine Progressive calcification of the cervical region of the spine occurs with age [2]. 3.3.7. Cardiovascular In Cohen’s series of 55 Apert syndrome patients, 9% had cardiovascular defects of various kinds [2]. No specific cardiovascular defect has been identified in Apert syndrome. 3.4. Ophthalmic manifestations 3.4.1. Proptosis / exophthalmos The proptosis occurring in Apert syndrome is pri-
219
marily related to the reduced volume of the bony orbital space. The decrease in the development of the maxilla results in a decrease in the size of the orbital floor. Proptosis also appears to be more prominent due to the midfacial hypoplasia of these patients [2,8]. 3.4.2. Lids /palpebral fissure The characteristic lid appearance in Apert syndrome is a horizontal downward displacement of the lateral canthi with a corresponding S-shaped upper lid configuration [l]. This results in lid laxities and malformations such as ectropion and entropion. 3.4.3. Interpupilla y distance In Apert patients, there is an increase in the distance between the medial walls of the orbits which is termed orbital hypertelorism [8].The distance between the lateral canthal walls, described clinically as interpupillary distance, is also secondarily increased in these patients. 3.4.4. Cornea The most common corneal manifestation is a chronic superficial punctate keratitis secondary to exposure [2]. The abnormal lid configuration and proptosis decreases the coverage of the eye and results in severe drying of corneal and conjunctival surfaces. If lubricants are not used, there can be severe ulceration, scarring, and vascularization. Keratoconus has also been described in Apert syndrome but a statistical analysis has not been done to determine if these patients are at a higher risk for the disorder [8]. 3.4.5. Ocular motility Strabismus is a common occurrence in Apert syndrome. The most frequent type of misalignment is exotropia [2,8]. A V-pattern of motility is also very common, with exotropia in upgaze, orthophoria in primary gaze, and esotropia in downgaze [2]. Several theories exist for the mechanism of strabismus in these patients. A likely explanation suggests that the decrease in orbital space with the compression of the soft tissue structures results in strabismus. 3.4.6. Optic nerve An increase in intracranial pressure often precedes the premature closure of cranial sutures. If this pressure remains high for a significant amount of time, papilledema can occur, potentially leading to optic atrophy [8]. Researchers disagree about the etiology of the optic atrophy that is seen in craniosynostosis patients. Some feel that in order to have optic atrophy one must have had increased intracranial pressure at
220
M.J. Melott / Clinical Eye and !&ion Cave 11 (1999)215-220
some time during their life. Others believe that it is not necessary to have had an episode of papilledema to have optic atrophy [2].
3.4.7. Retinal vascularity There is an increased frequency of retinal vascular tortuosity in Apert patients. Some authors believe that the tortuosity is evidence of previous papilledema 121. 3.4.8. Repactive error Some theories have suggested that hyperopia would be more common in Apert patients. However, one must consider not only the shallow orbit but also the lid configuration and corneal curvature when analyzing potential refractive errors in these patients. With all these considerations, hyperopia and myopia have been found to be of similar incidence in Apert syndrome [2]. 4. Management
The initial treatment for craniosynostosis is a cranio-orbital decompression surgical procedure. This procedure has the highest success rate if performed before the age of 11 months [1,2]. The surgical procedure actually releases the prematurely fused sutures of the skull. If the operation is performed at an early stage as suggested, normal development can proceed [2]. Careful follow-up of the patient is necessary, including regular eye examinations. Any signs of increased intracranial pressure would signify the need for a repeat of the decompression procedure. If the
Apert patient does not undergo a surgical procedure at an early age, the benefits of the procedure are minimized [1,2,6]. 5. Summary
Apert syndrome is a rare disorder involving craniosynostosis, ocular abnormalities and syndactyly. Ocular abnormalities in Apert syndrome results from the malformation of surrounding bony orbits. The ocular pathology of craniosynotosis is potentially threatening to the visual function of these patients. Vision loss is often preventable if it is recognized and treated appropriately. References 111 Posnick J. The craniofacial dysosotosis syndromes, staging of reconstruction and management of secondary deformities. Clin Plast Surg 1997;24(3):429-433. 121 Cohen Jr. MM. Craniosynostosis: diagnosis, evaluation, and management. New York: Raven Press, 1986:227-243. 131 Fatt HV, Griffin JR, Lyle WM. Genetics for primary eye care practitioners. 2nd ed. Boston: Butterworth-Heinemann, 1992:118-136. 141 Cohen MM Jr, Kreiborg S. Unusual cranial aspects of Apert syndrome. J Craniofac Genet Dev Biol 1994;14:48-56. 151 Agur AMR, Lee M. Grant’s atlas of anatomy. 9th ed. Baltimore: Williams & Williams, 1991. 161 Kreigborg S, Cohen Jr. MM. The oral manifestations of Apert syndrome. J Craniofac Genet Dev Biol 1992;1241-48. 171 Anderson PJ, Hall CM, Evans RD, Jones BM, Hayward RD. The feet in Crouzons syndrome. J Craniofac Genet Dev Biol 1997;17:43-47. 181 Paven-Langston MD. Manual of ocular diagnosis and therapy. 3rd ed. Boston: Little, Brown and Company.