|Year : 2021 | Volume
| Issue : 3 | Page : 588-590
Growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome: A rare cause of optic atrophy of optic atrophy
Aditya Sethi1, Sahebaan S Sethi2
1 Consultant, Paediatric Ophthalmology Services, Arunodaya Deseret Eye Hospital, Gurugram, Haryana, India
2 Consultant, Glaucoma Services, Arunodaya Deseret Eye Hospital, Gurugram, Haryana, India
|Date of Submission||31-Oct-2020|
|Date of Acceptance||27-Feb-2021|
|Date of Web Publication||02-Jul-2021|
Dr. Aditya Sethi
Arunodaya Deseret Eye Hospital, Plot NH4, Sector 55, Gurgaon, Haryana - 122011; Home address: C.2, Maharani Bagh, New Delhi - 110 065
Source of Support: None, Conflict of Interest: None
This case reports on a 21/2-year-old male child with GAPO syndrome, a rare autosomal recessive condition characterized by growth retardation (G), alopecia (A), pseudoanodontia (P), and optic atrophy (O). Since Anderson and Pindborg in 1947 first described this syndrome, close to 30 individuals have been reported with this diagnosis. Often a history of consanguinity is noted, as in our case, in this rare autosomal recessive condition. The phenotype of this condition, initially thought to be a result of ectodermal dysplasia, can be attributed to the accumulation of extracellular connective tissue matrix and its progressive character must be pointed out. The clinical findings, ophthalmological features that include optic atrophy, glaucoma, are reviewed and discussed.
Keywords: Alopecia, autosomal recessive disorder, ectodermal dysplasia, glaucoma, growth retardation, optic atrophy, Pseudoanodontia
|How to cite this article:|
Sethi A, Sethi SS. Growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome: A rare cause of optic atrophy of optic atrophy. Indian J Ophthalmol Case Rep 2021;1:588-90
|How to cite this URL:|
Sethi A, Sethi SS. Growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome: A rare cause of optic atrophy of optic atrophy. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Jul 29];1:588-90. Available from: https://www.ijoreports.in/text.asp?2021/1/3/588/320072
Growth retardation-alopecia-pseudoanodontia-optic atrophy (GAPO) syndrome is a form of ectodermal dysplasia, hypothesized to be autosomal recessive in nature, based on parental consanguinity and case reports of affected siblings. It is a rare developmental disorder with main manifestations of growth retardation (G), alopecia (A), pseudoanodontia (P), and optic atrophy (O). Andersen and Pindborg from Denmark first reported this rare syndrome in 1947. Tipton and Gorlin in 1984 established the GAPO syndrome as a distinct entity on the basis of four other similar cases reported from Brazil and Israel, as well as one of their own from the USA. Fewer than 30 such cases of GAPO syndrome have been reported in the literature since 2008.
Patients may also have premature closure of skull sutures, a prematurely aged appearance, hypogonadism, and hepatomegaly in addition to the classical manifestations. Very few case reports have described the ophthalmological findings and the pathophysiology of this autosomal recessive disorder.,, Optic atrophy is not a constant finding in GAPO syndrome. Other ophthalmic findings may include glaucoma.,,,
Until very recently, gene alterations in the ANTXR1 gene in these patients were pointed as the causative mutation. This gene encodes a matrix-interacting protein which acts as an adhesion molecule, and its mutation leads to either ectodermal dysplasia or the accumulation of extracellular connective tissue matrix.,, Current research shows the presence of elastin defect and secondary changes in collagen may be important in the pathogenesis of the disease.
In this case report, we give a detailed ophthalmological and neuro-ophthalmological description in a patient suffering from GAPO syndrome from the Southern part of India.
| Case Report|| |
A 2.5-year-old male child diagnosed by his pediatrician with GAPO syndrome, after characteristic phenotype and later genetic testing for ANTXR1 gene mutation, from a multi-specialty children's hospital. He came as a referral for ophthalmic evaluation in view of suspected raised intracranial pressure. The mother had complained that the child had difficulty in picking up things from the ground. She gave a vague history of headaches on and off, since a few months. There was no history of neck rigidity, projectile vomiting, loss of consciousness or any seizures.
The mother gave no history of any antenatal, intranatal or postnatal infection or complications. Child was born at full term to an elective cesarean section delivery. His birth weight was 3 kg. Child cried normally at birth. There was a history of third-degree consanguinity between the parents. The child had an elder sibling who faced no such developmental problems.
Previously, X-ray lateral view scan of skull showed micrognathia with non-eruptions teeth. Recent CT scan brain showed significant thickening and enlargement of optic nerve sheaths. Although MRI revealed brachycephaly with signs of raised intracranial pressures with wide-open bulging fontanelle with prominent subarachnoid spaces and signs of mild thinning of optic nerves of both eyes with hyperintensity in T2 in the center of the right optic nerve.
On general examination, child was afebrile, alert, playfully. He had frontal bossing, broad nasal bridge and had a bulge in anterior fontanelle. Mother gave history of child being born with hair and then later having episodes of alopecia [Figure 1], and also of mouth breathing. Child had signs of delayed developmental milestones and growth retardation ([Figure 2] showing pseudoanodontia).
|Figure 1: Photo (External) showing features of high and bossed forehead, mid-face hypoplasia, alopecia|
Click here to view
Child could fixate and follow light and objects briskly with both and either eye(s). On Hirschberg test, the images were central in both eyes. On doing cover test the child had a central steady and maintained fixation in ether eye for both distance and near assessment. Extra-ocular movements revealed no limitation in any direction of the nine gazes. There was no nystagmus appreciated. Pupils were round, regular and reacting to light briskly in both eyes.
He had corneal horizontal diameter of Right Eye 12.1 mm and Left Eye 12.2 mm. Intraocular pressure (IOP) examination by Perkins tonometry revealed pressures of 22 mm Hg and 20 mm Hg in the right eye and left eye, respectively. Pachymetry was an average of 514 micrometers in both eyes. Gonioscopy done in both eyes showed open angles in each quadrant to scleral spur with iris processes present and trabecular meshwork pigmentation.
Dilated cycloplegic refraction revealed a correction of +0.00 DS/-3.00 DC ×180 in each eye. Fundus examination by both +90 D slit-lamp ophthalmoscopy and indirect ophthalmoscopy revealed vertical cup disc ratio of 0.8:1 in the right eye, 0.65:1 in the left eye and disc pallor in both eyes [Figure 3]. Flash visually evoked potential (VEP) was done and recorded normal P2 latencies and normal amplitudes in both eyes [Figure 4]a.
|Figure 4: VEP (Visual Evoked Potential) results from (a) 2010, (b) and (c) 2013|
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Child was prescribed glasses for full-time use and regular cycloplegic refraction was done at subsequent follow-ups.
With consideration of the systemic status, the child was started on timolol 0.5% eye drops twice a day along with punctual occlusion and was recalled after 2 months for reassessment of IOP. The child was also started on oral acetazolamide 125 mg once a day by his neurosurgeon, for raised ICT, eventually to be stopped after 1 month. On his next visit, IOP measured with Perkins tonometer was found to be 22 mm Hg and 18 mm Hg in right and left eye, respectively. The mother was advised to start him on dorzolamide 2% eye drops twice a day instead of the timolol eye drops that she had been administering. Child was kept in close follow-up at 3 months intervals for the next year and the IOP was maintained at target level and no progressive disc damage observed.
Child had gradual progressive visual difficulty for distance and near in both eyes, noted since the first visit. Low Vision assessment and Vision therapy were advised but not much benefit achieved. Subsequently, child developed very low vision in both eyes, the right more than the left eye.
Repeat VEP both flash and pattern was done. Flash VEP in the right eye showed no recordable waveforms and in the left eye showed normal P2 latency but reduced amplitude [Figure 4]b. Pattern VEP in the left eye showed a marked delay in P1 latency and reduced amplitudes [Figure 4]c. Repeat MRI and MRV scans were done, confirming features suggestive of optic atrophy and brachycephaly. MRV didn't show any additional significant abnormalities.
| Discussion|| |
In all previously documented patients with GAPO syndrome growth retardation, alopecia, and pseudoanodontia were present. However optic atrophy was the most inconsistent feature among the 30 odd cases published of GAPO syndrome so far. Other ophthalmological findings associated with GAPO syndrome include glaucoma, ptosis, nystagmus, strabismus, myopia, megalocornea, bilateral keratoconus, band keratopathy, unilateral corneal abscess, hypermature cataract, and retinoschisis, retinal vein dilation, and papilledema.
General features of growth retardation with delayed bone age in infancy and characteristic facial features (high and bossed forehead, mid-face hypoplasia), alopecia, and pseudoanodontia were all present in our presenting case correlating with other case reports in the literature. The mental state was normal in our case and in the cases described in the literature.
Our patient showed signs of optic disc pallor in both eyes, which has been reported previously in literature with GAPO syndrome. Optic disc atrophy,,,, being the least consistent of the findings has been reported only in five cases in the literature in the past. Papilledema has also been reported in the literature in patients with GAPO syndrome.,, Autopsy studies by Wajntal et al. suggest optic atrophy and loss of retinal ganglion cells secondary to optic nerve constriction secondary to thickening dura mater.
VEP tests showed variable results in the literature, from no changes to impairments noted which were also reported in our patient. Glaucoma has been reported to be associated with GAPO syndrome commonly in literature,,, and was also reported in our patient. It has been hypothesized in the literature that an increase in production, decrease in breakdown or both of extracellular matrix contributed to an excessive deposit to and loss of trabecular cells leading to the development of an open-angle type of glaucoma (OAG) in these cases.
Retinal venous dilatation was reported in only one case in literature and was not a feature in our patient. Other ophthalmological findings reported in the literature include interstitial keratitis, keratoconus and band-shaped keratopathy among other notable findings.
| Conclusion|| |
We have reported a rare case of GAPO syndrome, features and associations of which ophthalmologists should be aware of.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]