Microphthalmos, orbital cyst, and missing thumbs: A rare case report.

A 5-month-old girl was presented to us with a right orbital cyst covering a microphthalmic eye, absent digits (thumbs) in both hands, and absence of right radius and left kidney. The hematological profile of the patient was within normal limits. The patient had a family history of leukemia and the chromosomal analysis was suggestive of Fanconi's anemia (FA). The cyst was excised in toto and sent for histopathology. To the best of our knowledge, this is the first case report of an orbital cyst covering a microphthalmic eye in a patient with FA. This case report also stresses the fact that FA can be missed by ophthalmologists in the patients with congenital microphthalmos and missing thumbs and efforts should be made to avoid doing so.

Introduction

Fanconi's anemia (FA) is an autosomal recessive (rarely X-linked) DNA repair disorder, characterized by progressive bone marrow failure, defective hematopoiesis, various congenital malformations, an increased risk of acute myeloid leukemia and solid malignancies, as well as various dermal pigmentary changes.[1] The prevalence of this condition is 1–5 cases/million.[2] DNA repair disorder leads to chromosomal instability causing increased mutagenesis, accumulation of DNA damage, increased susceptibility to exogenous DNA damaging agents, and induces the apoptosis of hematopoietic stem cells resulting in their depletion.[3] Fifteen FANC genes have been identified so far, the most prevalent being FANCA, FANCC, FANCG, and FANCD2.[4]

A wide range of ocular findings have been described in the international literature in the patients with FA which include microcornea, microphthalmos, cataract, ptosis, congenital glaucoma, phacomorphic glaucoma, dermal pigmentary changes, strabismus, epicanthus, telecanthus, small optic disc, accommodation problems, ocular motor dysfunction, retinoblastoma and retinal occlusive vasculopathy leading to retinal and optic disc neovascularization.[15]

We report a case of FA presenting with an orbital cyst and underlying microphthalmos, a clinical association that to the best of our knowledge has never been reported in the international literature before. This case report also lays emphasis on the inclusion of FA in the associated systemic anomalies of patients with congenital microphthalmos and missing thumbs.

Case Report

A 5-month-old girl, weighing 5.4 kg and measuring 26 inches, was presented to us with a large cyst along the floor of the right orbit since birth. She was born at a gestational age of 39 weeks. The parents of the patient were first cousins and the patient had three normal siblings. The grandmother of the patient had died of leukemia at the age of 50 years and the father had also developed leukemia at the age of 35 years and later died of it. A 17-year-old cousin of the patient also died of leukemia. On clinical examination, the patient had a unilateral, right bluish cyst, measuring 4 cm × 3 cm × 1 cm, covering the right eye completely [Figure 1]. Slit lamp examination of the left eye showed a normal anterior and posterior segment, an intraocular pressure of 14 mm of Hg, and normal angles on gonioscopy. The thumbs were absent in both the hands. Blood tests of the patient showed no evidence of any metabolic disorder or coagulopathy and were within normal limits. The computed tomography scan of the right eye showed a cystic lesion having fluid in it and covering a microphthalmic eye [Figure 2]. X-ray of the hands revealed the absence of thumbs in both hands and the radius in the right forearm [Figure 3]. Magnetic resonance imaging of the abdomen showed absence of the left kidney [Figure 4]. Cytogenetic studies were performed on peripheral blood lymphocyte cultures stimulated with phytohemagglutinin and induced with mitomycin C (40 ng/mL). Standard procedures were used to obtain chromosomal preparations, which were subjected to Giemsa-Trypsin banding. A high frequency of chromosomal breakage was revealed on chromosomal analysis (30% of the examined metaphases had chromosomal aberrations). The patient was diagnosed as a case of FA.

Figure 1

The patient having a bluish cyst, measuring 4 cm × 3 cm × 1 cm and covering the right eye completely

Figure 2

The computed tomography scan of the right eye showing a cyst covering a microphthalmic eye

Figure 3

X-ray of hands showing absence of thumbs in both hands and absence of radius in the right forearm

Figure 4

Magnetic resonance imaging of abdomen showing absence of the left kidney

The cyst was excised with preservation of the microphthalmic. 6 years have passed since the patient was presented to us, and is being followed up on a regular basis with a pediatric ophthalmologist, medical specialist, rheumatologist, hematologist-oncologist, and a genetic counselor. Routine blood cell counts, surveillance of bone marrow failure, and development of malignancy is mandatory in this patient. The patient has been advised with protective polycarbonate glasses and is doing fine clinically to date except for the fact that she has developed a right-hand deformity following a trivial trauma. Two of her first cousins, aged 19 and 21 years, respectively, have been diagnosed with leukemia recently and are being treated for it.

Discussion

A MEDLINE search using keywords “ocular associations” and “FA” revealed three articles.[125] Yahia et al. reported a case of ocular neovascularization in a patient of FA.[2] Tsilou et al. conducted a cross-sectional study of 75 patients having Inherited Bone Marrow Failure Syndromes. Among them, 22 patients had FA having a wide range of ocular associations.[5]

The differential diagnosis, in this case, included thrombocytopenia-absent radius syndrome, trisomy 18, VATER/VACTERL syndrome, and Holt–Oram syndrome.[6] A child with microphthalmos and missing thumbs should be examined with a high index of suspicion for FA. European registries have reported that associated systemic anomalies are present in 40–73% of individuals with congenital microphthalmos. Tucker et al. encompassed a wide range of systemic anomalies in the 77 patients that he studied with congenital microphthalmos, including several central nervous system, gastrointestinal, cardiac, genitourinary, face, ear, and skeletal anomalies.[7] A child with microphthalmos/orbital cyst with missing thumb must be evaluated to rule out this serious premalignant disorder.

Alongside missing thumbs and microphthalmia, a highly suspected child presents with aplastic anemia and characteristic birth defects. Intermediate suspicion includes a child with characteristic birth defects only, whereas a low but real level of suspicion includes children with skin pigmentation.[8] Our patient was included in the intermediate suspicion category.

Alter blood pressure concluded that a patient with FA can have a wide range of malignancies[9] [Table 1]. Furthermore, apart from malignancies; various ocular anomalies are found in overall 23% of the cases of FA [Table 2].[8] Our patient had a family history of leukemia whereas other systemic malignancies were not reported to date in any member of the patient's family. It is also worth mentioning here that the absence of radii in the patients of FA may make them very prone to hand deformities’ following minor traumas as was the case in our patient.

Table 1

Associated malignancies in Fanconi's anemia[9]

Table 2

Ocular associations of Fanconi's anemia

Consulting a genetic health professional may be helpful in determining relevant testing and carrier risk. Genetic testing helps in determining medical management, prognosis, mode of inheritance, and excluding diseases with similar manifestations. The implications of a positive test for a gene mutation should be discussed with the physician or a genetic health professional and appropriate testing for the reproductive partner and at-risk family members should be performed. A negative test reduces but does not completely eliminate the possibility of an individual carrying a gene mutation.

The clinical course of FA is fraught with serious life-threatening complications. Hematopoietic growth factors, androgen therapy, bone marrow transplantation, preimplantation genetic diagnosis and prevention, surveillance, early detection, and treatment of malignancies are general standards of care for FA patients from a physician's point of view.[3] The mean survival age is about 16 years. The increased susceptibility to malignancies leads to the grave biological course for children suffering from FA.[10] We have been following up our patient for the last 6 years and so far the child is doing fine clinically to date.

Conclusion

Children with congenital microphthalmos and missing thumbs should always be investigated for FA, which can be missed by ophthalmologists. Furthermore, we are unaware of the reported cases of orbital cyst covering a microphthalmic eye in the patients of FA. Therefore, microphthalmos with orbital cysts should also be included in the ocular associations of FA.

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

Nil.

Conflicts of interest

There are no conflicts of interest.