Neurofibromatosis (NF) is an autosomal dominant genetic disease that causes multi-system damage. It is caused by abnormal neural crest cell differentiation and can be divided into NFI and NFII. This case is NFI, which is related to mutations in the gene at 17q11.2 . The incidence is about 1/4000 worldwide. It can involve multiple organs and tissues such as the skin, cardiovascular system, orthopedic system, and digestive system. The manifestations of the disease can be very different, even within the same family .
For a case to be diagnosed as NFI, at least two of the following criteria must be met : 1) Six or more coffee-milk macules; 2) two or more neurofibromas of any type or one plexiform neurofibroma; 3) freckling in the axillary or inguinal regions; 4) optic nerve glioma; 5) two or more iris Lisch nodules; 6) a distinctive osseous lesion (e.g., sphenoid wing dysplasia, long bone cortical thinning with or without pseudoarthrosis); 7) a first-degree relative who meets the criteria for NF1. The patient had subcutaneous neurofibroma at the occipital bone, multiple coffee and milk spots on the neck and back, and Lisch nodules in the eye. The symptoms were typical and consistent with the diagnosis of neurofibroma type I.
The clinical manifestations of NFI are complex and diverse, and they can involve one or more organs. The involved eye tissues often appear as eyelid plexiform neurofibroma, intraorbital tumors, iris changes, ciliary body fibroma, and choroidal pigment nevus. Unilateral congenital glaucoma can be the first symptom of the disease, and it can be very easy to miss. However, the pathogenesis of this glaucoma is still unknown, and the main considerations are currently related to the following factors: 1) neurofibromas directly block anterior chamber angle; 2) developmental angle abnormalities; 3) secondary angle closure by neurofibromatous cysts or a thickening of the ciliary body and choroid; 4) neovascular glaucoma.
The initial eye symptom of this case was glaucoma in the right eye, but both eyes were involved. The inferior temporal angle of the left eye was closed, and there was a point-like hyperechoic echo at the corresponding part of the ciliary body. It is speculated that neurofibroma involves the temporal and inferior ciliary body and finally leads to the closure of the angle. However, there were no abnormalities in the ciliary body, eyelid, intraorbital, choroid, or retina of the right eye. Pathology shows an aggregation of endothelial-like cells on the surface of trabecular meshwork. Therefore, we speculate that the pathogenesis of this patient’s glaucoma in the right eye may have two causes: 1) A large number of peripheral iris nodules directly block the angle; 2) proliferation of endothelial cells at the iris and the angle, trabecular meshwork obstruction, and pre-iris adhesion, affecting aqueous drainage leads to increased intraocular pressure, which further aggravates the pre-iris adhesion , forming a positive feedback cycle. Although the intraocular pressure in the left eye is normal, the changes of the left eye should be closely monitored at a later stage.
The right eye iris, in this case, has obvious Ectropion uveae near the pupillary edge. Ectropion uveae often prompts severe glaucoma in children, which may be related to the overexpression of Ras–MAPK gene causing the endothelial cells to accumulate in the angle and anterior iris . Glaucoma surgery for ectropion uveae has a lower success rate than surgery for simple congenital glaucoma, and this difference may be related to severe angular dysplasia .
The incidence of NFI with congenital glaucoma is low and clinically rare. Glaucoma can be its first symptom and is easily missed. In this patient, due to early detection, less eye tissue involvement, and relatively mild symptoms, intraocular pressure was ideally controlled after simple trabeculectomy, but long-term efficacy still needs to be followed up.