developmental and epileptic encephalopathy, 85, with or without midline brain defects

Developmental and epileptic encephalopathy, 85, with or without midline brain defects is a severe neurodevelopmental condition that primarily affects the brain, leading to seizures and developmental challenges. This disorder is caused by pathogenic variants in the SMC1A gene and follows an X‐linked dominant inheritance pattern, meaning that many cases arise as new (de novo) changes. Affected individuals often present in infancy with significant neurological impairment and complex physical features, and precise prevalence estimates are not well established. Modern care continues to evolve, improving our understanding and management of this condition.

The clinical presentation includes a spectrum of neurological and physical features. Nearly all affected individuals experience infantile spasms, hypsarrhythmia, and various types of seizures, including bilateral tonic-clonic seizures, which reflect the disorder’s profound neurological impact. Facial dysmorphisms such as highly arched eyebrows, retrognathia, triangular and round faces, a short and narrow nose, together with dental crowding, are consistently observed. Motor difficulties are common, with generalized and axial hypotonia, spastic tetraparesis, scoliosis, a delayed ability to walk, and motor stereotypies forming part of the picture. Communication challenges are evident, including delayed speech and reduced eye contact. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the SMC1A gene, which plays a crucial role in chromosome cohesion and the regulation of gene expression during development. It is inherited in an X‐linked dominant pattern, and most cases arise from de novo mutations, meaning there is usually no prior family history. Affected individuals can pass the variant to their offspring, and since females typically manifest symptoms due to skewed X‐inactivation, genetic counseling is recommended to discuss family planning and recurrence risks.

Currently, management focuses on supportive care and symptom management rather than curative treatment. A multidisciplinary team approach is crucial for addressing the range of neurological, developmental, and physical challenges seen in affected individuals. Supportive therapies such as physical therapy, occupational therapy, and educational interventions, along with comprehensive seizure management, form the cornerstone of care. Regular surveillance is an essential part of long-term management, helping to identify potential complications early. Patients should discuss treatment options with their healthcare team to determine which therapies may be most appropriate, and genetic counseling is recommended to help families navigate the implications of this condition.

The condition is lifelong and characterized by an initial phase of developmental regression followed by a period of relative stabilization, with some individuals potentially experiencing later motor decline. Severity and symptoms vary widely between affected individuals, and outcomes depend on factors such as the severity of symptoms, the age at diagnosis, and access to specialized care. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition to stay informed about management strategies and supportive resources.