In “Septo-Optic-Pituitary Dysplasia Is a Clinical Syndrome, Not a Neuropathological Entity: An Autopsy-Based Study,” Drs. Salman and Del Bigio outline neuropathological findings from autopsies of patients with clinical features of septo-optic-pituitary dysplasia (SOD). ^{Reference Salman and Del Bigio1} They describe the syndromic nature of SOD including hypothalamic-pituitary dysfunction, absent septum pellucidum (SP) and/or abnormal corpus callosum (CC), in addition to optic nerve hypoplasia (ONH). This report demonstrates the importance of clinicopathological studies to practicing clinicians.

The study provides descriptions of the anatomical abnormalities underlying the clinical manifestations of this condition. The authors have determined that not all cases thought to represent SOD are SOD (11/21 of their patients did not have SOD by definition), and conversely, SOD can have variable clinical findings and etiologies. They have established that ONH is the sine qua non of SOD.

This is important reading for pediatric neurologists who, when confronted with an infant exhibiting signs and symptoms of hypothalamic-pituitary dysfunction, visual or hearing loss or seizures, must determine if there is clinical evidence of ONH and, beyond that, abnormal CC or absent SP. This then raises the possibility of a perinatal or in utero hypoxic-ischemic event or infection, which was the most common cause of the syndrome in this study, similar to previous reports. ^{Reference Ryabets-Lienhard, Stewart, Borchert and Geffner2}

Three of their patients with SOD were 16 years of age or older but had long-standing neurological issues. As a clinician seeing patients with ONH, often unsuspected, adult patients can have variable presentations, including long-standing unilateral or bilateral visual impairment or atypical congenital nystagmus. Excluding patients with segmental disc hypoplasia or atrophy, and using the criterion of disc to macular distance to disc diameter ratio of greater than 3, ^{Reference Zeki, Dudgeon and Dutton3} patients may be diagnosed with ONH who are otherwise neurologically intact. In these patients, looking for absent SP, abnormal CC or hormonal dysfunction is important. Conversely, neurologists might be asked to see a patient who has already had an MRI showing abnormal CC or absent SP, found serendipitously during investigations for other neurological symptoms, such as headaches or seizures. They must look for ONH to secure the diagnosis and determine if there is hypothalamic-pituitary dysfunction. In both cases, discovering a family history may be critical for the health of future generations.

This paper provides the basis for a diagnosis of individuals presenting with only partial manifestations of SOD and for determining the cause of symptoms that may otherwise remain obscure.