Introduction: Holoprosencephaly (HPE) sequence is a rare brain malformation caused by incomplete division of the forebrain during early embryonic life. It shows a wide spectrum of severity and is commonly associated with characteristic midline craniofacial anomalies. Although many cases are linked to chromosomal disorders and multisystem syndromes, isolated holoprosencephaly with a normal karyotype is uncommon. About twelve percent of cases are non-syndromic and linked to pathogenic variants in SHH, ZIC2, SIX3, and TGIF genes, most often affecting the Sonic hedgehog signalling pathway , with variable clinical expression. Case presentation: We report a two-month-old infant born to healthy non-consanguineous parents with a healthy sibling, who presented with recurrent subtle motor seizures. Typical facial features were present, including hypotelorism, microphthalmia, cleft lip and palate, microcephaly , and absence of the philtrum and nasal septum. Brain imaging confirmedholoprosencephaly with agenesis of the corpus callosum. Chromosomal analysis was normal (46,XX). Radiology showed no significant renal structural anomalies or gallbladder agenesis. Endocrine evaluation excluded hypopituitarism, and no hypoglycaemic episodes occurred. Seizures were partially controlled with multiple anticonvulsants, with burst-suppression on EEG.Nutritional support was provided via nasogastric feeding. Hearing and vision assessments were reassuring, with no cataracts, coloboma, or sensorineural hearing loss. Cardiac assessment revealed a small ASD. No genitourinary , skeletal, neural tube were identified. Chest radiography showed no diaphragmatic hernia or thymic hypoplasia. Despite optimal supportive care, theinfant demonstrated suboptimal growth and weight gain. Conclusion: Non-syndromic isolated holoprosencephaly sequence requires detailed genomicevaluation for prognostication ,family counselling and multidisciplinary interventions.