Optic Nerve Hypoplasia, Bilateral

A number sign (#) is used with this entry because of evidence that bilateral optic nerve hypoplasia and aplasia can be caused by heterozygous mutation in the PAX6 gene (607108) on chromosome 11p13.

Clinical Features

Optic nerve hypoplasia is the most common congenital anomaly of the optic disc (Birkebaek et al., 2003). It may be an isolated finding or part of a spectrum of anatomic and functional abnormalities that includes partial or complete agenesis of the septum pellucidum, other midline brain defects, cerebral anomalies, pituitary dysfunction, and structural abnormalities of the pituitary. Hypopituitarism is a serious problem, and failure to recognize it carries a risk of adrenal crisis, hypoglycemia, and death (Brodsky et al., 1997; Cameron et al., 1999). Septooptic dysplasia (182230) describes the association of optic nerve hypoplasia with absent septum pellucidum, with or without pituitary dysfunction.

Hackenbruch et al. (1975) described bilateral optic nerve hypoplasia in 5 persons in 4 generations with male-to-male transmission. The affected persons had poor visual acuity, small discs, 2 concentric peripapillary halos, and wandering movements of the eyes. Two previous reports of familial occurrence, in sibs, were cited.

In a study group comprising 55 optic nerve hypoplasia patients, Birkebaek et al. (2003) reported that 49% had an abnormal septum pellucidum on MRI, and 64% had a hypothalamic-pituitary axis abnormality. Twenty-seven patients (49%) had endocrine dysfunction, and 23 of these had hypothalamic-pituitary axis abnormality. The frequency of endocrinopathy was higher in patients with an abnormal septum pellucidum (56%) than a normal septum pellucidum (39%). Patients were divided into 4 groups based on septum pellucidum and hypothalamic-pituitary axis appearance: (1) both normal; (2) abnormal septum pellucidum and normal hypothalamic-pituitary axis; (3) normal septum pellucidum and abnormal hypothalamic-pituitary axis; and (4) both abnormal. The frequency of multiple pituitary hormone deficiency was highest (56%) in group 4, lower (35%) in group 3, and even lower (22%) in group 2. Precocious puberty was most common in group 2. None of the patients in group 1 had endocrine dysfunction. The authors concluded that septum pellucidum and hypothalamic-pituitary axis appearances on MRI can be used to predict the likely spectrum of endocrinopathy.

Molecular Genetics

Azuma et al. (2003) identified mutations in the PAX6 gene in patients with bilateral optic nerve hypoplasia (607108.0018) and aplasia (607108.0020).