Marbach-Schaaf neurodevelopmental syndrome

Marbach-Schaaf neurodevelopmental syndrome is a condition that primarily affects neurological development and function. It is associated with pathogenic variants in the PRKAR1B gene, which plays a role in cellular signaling processes. The syndrome is inherited in an autosomal dominant manner, meaning that a single altered gene copy can cause the condition. Although precise prevalence estimates are not established, the syndrome is identified based on its characteristic neurodevelopmental features.

The clinical presentation of Marbach-Schaaf neurodevelopmental syndrome includes consistent features such as neonatal hypotonia, global developmental delay, attention deficit hyperactivity disorder, autistic behavior, speech apraxia, and delayed speech and language development. Additionally, a number of less common features have been reported, including epicanthus, aggressive behavior, obstructive sleep apnea, and subtle craniofacial characteristics like upslanted palpebral fissure and depressed nasal bridge among others. That not all individuals experience every feature and severity can vary considerably.

This condition is caused by pathogenic variants in the PRKAR1B gene, which is crucial for proper cell signaling. Marbach-Schaaf neurodevelopmental syndrome is inherited in an autosomal dominant pattern, meaning that a single copy of the altered gene can result in the syndrome and affected individuals have a 50% chance of passing the variant on to their offspring. Genetic counseling is advised for families to fully understand the implications of this inheritance pattern.

Currently, management focuses on supportive care and symptom management, with treatment plans tailored to address each individual's unique challenges. A multidisciplinary approach is central to care, often involving interventions such as speech therapy, occupational therapy, and behavioral support. Ongoing surveillance and regular assessments by specialists help to address evolving needs over time. Genetic counseling is recommended to assist families in understanding treatment options and implications for family planning, with care decisions being made in collaboration with the healthcare team.

Marbach-Schaaf neurodevelopmental syndrome is a lifelong condition characterized by early neurodevelopmental challenges. Outcomes vary widely between individuals, with some experiencing stabilization of symptoms over time while others may require ongoing support into adulthood. With current standards of care and multidisciplinary management, many individuals achieve improvements in quality of life despite persistent developmental challenges. Families are encouraged to connect with specialists and genetic counselors for ongoing support as outcomes continue to evolve with advances in care.