Retinoblastoma is a malignant tumor of the developing retina that occurs in children, usually before age five years. Retinoblastoma may be unifocal or multifocal. About 60% of affected individuals have unilateral retinoblastoma with a mean age of diagnosis of 24 months; about 40% have bilateral retinoblastoma with a mean age of diagnosis of 15 months. Heritable retinoblastoma is associated with susceptibility for retinoblastoma as well as non-ocular tumors.

Osteoporosis-pseudoglioma syndrome (OPPG) is an autosomal recessive disorder characterized by severe osteoporosis and visual disturbance from childhood. Juvenile onset of osteoporosis manifests as long-bone fractures, vertebral compression fractures, kyphoscoliosis, deformity of extremities, and short stature. Congenital or early-onset visual disturbances arise from ophthalmologic problems including retinal detachment and microphthalmia (summary by Narumi et al., 2010).

FAM111A-related skeletal dysplasias include the milder phenotype of Kenny-Caffey syndrome (KCS) and a more severe lethal phenotype, osteocraniostenosis (OCS). KCS is characterized by proportionate short stature (typically postnatal onset), relative macrocephaly, large anterior fontanel with delayed closure, characteristic facial features, cortical thickening of the long bones with stenosis of the medullary cavity, and ophthalmologic and dental manifestations. OCS is characterized by intrauterine growth deficiency, microcephaly, characteristic facial features, decreased skull ossification, slender long bones with cortical thickening, stenosis of the medullary cavity of the long bones, flared metaphyses, and thin ribs with thoracic and pulmonary hypoplasia leading to respiratory insufficiency. Perinatal fractures may occur. Primary hypoparathyroidism with hypocalcemia and hyperphosphatemia can occur in individuals with KCS and OCS.