Madras motor neuron disease (MMND) is a rare childhood/juvenile motor neuron disease reported from various parts of southern India, the first report being from Chennai. This case report is about a young girl who presented with insidious onset, a gradually progressive neurological illness characterized by bilateral sensorineural hearing loss, wasting, and weakness of all four limbs along with bulbar paralysis. On examination, she had involvement of lower cranial nerves, tongue fasciculation, generalized amyotrophy, and bipyramidal features. Electrophysiological studies showed features of chronic denervation. A provisional diagnosis of MMND was made. MMND resembles Brown–Vialetto–Van Laere (BVVL) syndrome and some of the other complex childhood motor neuron disease syndromes, like Boltshauser syndrome, Nathalie syndrome, and Fazio–Londe syndrome. Early diagnosis of BVVL, which is a riboflavin transporter deficiency, is essential, as it is fully responsive to high-dose riboflavin supplementation. In BVVL syndrome, a female predominance has been documented (1:5), while in MMND, an equal distribution is noted. In BVVL, at least half of the reported cases are familial whereas in MMND most of the cases are sporadic. In BVVL, lower motor neuron signs in the limbs are infrequently present and pyramidal signs are rare, whereas in MMND lower and upper motor neuron signs are seen in the majority of the patients. Third, fifth, or sixth cranial nerves are never noted to be affected in MMND, but they may rarely be involved in BVVL. The etiopathophysiology of MMND is still unclear and supportive or symptomatic therapy forms the mainstay of treatment of this orphan disease.