Hearing and eyesight
A minority of those with Okamoto syndrome have had hearing loss of both sensorineural and conductive types, and a smaller minority have had optic nerve abnormalities. Cause
Okamoto syndrome is caused by a mutation in the HNRNPK gene, located on chromosome 9 at position q21.32. HNRNPK codes for heterogeneous nuclear ribonucleoprotein K. Ribonucleoproteins are proteins that form complexes with RNA, and they are involved in the transcription of DNA into RNA in the nucleus. They usually bind with precursor messenger RNA (pre-mRNA), which is messenger RNA that has not yet had its introns removed during splicing to be ready for translation. A mutation in one of the two copies of HNRNPK results in defects in DNA transcription, and therefore some developmental processes are disrupted or not completed.Mutations in HNRNPK that have been reported include nonsense mutations, in which the protein is truncated and usually non-functional as a result, frameshift mutations, splice-site mutations and microdeletions encompassing the gene. Rarely, missense mutations, in which one amino acid in the protein is replaced by another, have also been reported.Deletions in the region encompassing HNRNPK have been found in the cells of acute myeloid leukemia in approximately 2% of cases. Acute myeloid leukemia cells are immature white blood cells (myeloblasts) that remain in the stem-cell stage, dividing continually. Additionally, a 2015 study found that a majority of mice who had one of their HNRNPK genes artificially knocked out developed myeloid cancers, with a third developing lymphoid cancers and 4% developing hepatocellular carcinomas.
Medulloepithelioma is a rare, primitive, fast-growing brain tumour thought to stem from cells of the embryonic medullary cavity. Tumours originating in the ciliary body of the eye are referred to as embryonal medulloepitheliomas, or diktyomas.A highly malignant undifferentiated primitive neuroepithelial tumour of children, medulloepithelioma may contain bone, cartilage, skeletal muscle, and tends to metastasize extracranially. Signs and symptoms
Medulloepithelioma have been reported to occur in the cerebral hemispheres, brainstem, cerebellum, and peripheral sites.Due to rapid growth of the tumour, patients typically present with increased intracranial pressure, seizures, and focal neurologic signs. Diagnosis
Imaging studies such as Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) can aid diagnosis. Medulloepithelioma appears isodense or hypodense with variable heterogeneity and calcification on non-contrast CT scan, and enhances with contrast. This radiographical finding is consistent with a primitive neuroectodermal tumour, especially in children. Blood studies and imaging studies of the abdomen may be used to detect metastases.Needle aspiration biopsy can be used to aid diagnosis. Definitive diagnosis requires histopathological examination of surgically excised tumour tissues.Histologically, medulloepithelioma resemble a primitive neural tube and with neuronal, glial and mesenchymal elements. Flexner-Wintersteiner rosettes may also be observed.Immunohistochemically, neural tube-like structures are vimentin positive in the majority of medulloepitheliomas. Poorly differentiated medulloepitheliomas are vimentin negative. Classification
Medulloepithelioma was originally classified as the most primitive neoplasm of the Central Nervous System (CNS) by Bailey and Cushing in 1926. Rorke et al.