Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare adult onset autosomal dominant disorder characterized by cerebral white matter degeneration with demyelination and axonal spheroids leading to progressive cognitive and motor dysfunction. Spheroids are axonal swellings with discontinuous or absence of myelin sheaths. It is believed that the disease arises from primary microglial dysfunction that leads to secondary disruption of axonal integrity, neuroaxonal damage, and focal axonal spheroids leading to demyelination. Spheroids in HDLS resemble to some extent those produced by shear stress in a closed head injury with damage to axons, causing them to swell due to blockage of axoplasmic transport. In addition to trauma, axonal spheroids can be found in aged brain, stroke, and in other degenerative diseases. In HDLS, it is uncertain whether demyelination occurs prior to the axonal spheroids or what triggers neurodegeneration after apparently normal brain and white matter development, although genetic deficits suggest that demyelination and axonal pathology may be secondary to microglial dysfunction. The clinical syndrome in patients with HDLS is not specific and it can be mistaken for Alzheimers disease, frontotemporal dementia, atypical Parkinsonism, multiple sclerosis, or corticobasal degeneration. Symptoms
With symptoms of personality changes, behavioral changes, dementia, depression, and epilepsy, HDLS has been commonly misdiagnosed for a number of other diseases. Dementia or frontotemporal behavioral changes, for example, have commonly steered some clinicians to mistakenly consider diagnoses such as Alzheimers disease, frontotemporal dementia or atypical Parkinsonism. The presence of white matter changes has led to misdiagnosis of multiple sclerosis.
The German TV series Dr. Stefan Frank episode "Ein himmlisches Lächeln" (season 4, episode 4) is about a young boy living with Möbius syndrome. The book "Secret Weapon" of the Alex Rider series gives a mention to Darcus Drake, a man with Möbius syndrome. In “The Adventure of the Man Who Never Laughed”, a story written by John H. Watson, M.D./discovered by J. N. Williamson, and collected in Holmes For The Holidays, edited by Martin H. Greenberg, Jon L. Lellenberg and Carol-Lynn Waugh (Berkley Prime Crime, 1996), a missing person has Möbius syndrome. References
External links

Möbius syndrome at Curlie
Möbius syndrome at the National Institute of Neurological Disorders and Stroke