craniosynostosis 6

Craniosynostosis 6 is a congenital condition characterized by the premature fusion of one or more cranial sutures, leading to abnormal skull formation. This condition is caused by mutations in the ZIC1 gene, which plays a key role in craniofacial development. It is typically identified in infancy when abnormal head shape or craniofacial features are noted, although precise prevalence estimates are not established. Overall, the presentation and severity can vary considerably among affected individuals.

Individuals with craniosynostosis 6 most present with craniosynostosis, which is universally observed. Many children also exhibit a range of other features; for example, nearly one‐third to most may have bicoronal synostosis, hypotonia, microcephaly, ptosis, a high forehead, and strabismus. Less commonly, some individuals show skull shape variations such as brachycephaly, plagiocephaly, turricephaly, or a delayed closure of cranial sutures, while a subset may have additional findings including hypertelorism, Dandy-Walker malformation, spina bifida occulta, parietal foramina, lateral ventricle dilatation, scoliosis, low anterior hairline, agenesis of the corpus callosum, right unilambdoid synostosis, and sensorineural hearing impairment. Not all individuals experience all these features, and severity varies widely between individuals.

Craniosynostosis 6 is caused by pathogenic variants in the ZIC1 gene. This gene is integral to the regulation of craniofacial and neural development, and alterations in its function lead to premature fusion of skull sutures and related cranial abnormalities. The condition follows an autosomal dominant inheritance pattern, meaning that a single copy of the mutated gene can cause the condition. That even within the same family, the severity and specific features can vary considerably, a concept known as variable expressivity. Families are encouraged to seek genetic counseling to better understand inheritance risks and implications for family planning.

Currently, management of craniosynostosis 6 focuses on supportive care and addressing symptoms on an individual basis. While there are no FDA-approved or foundational therapies specifically linked to the condition, treatment is typically tailored to each patient’s needs and may involve surgical intervention to correct skull shape as well as therapies to address associated issues such as hypotonia or strabismus. A multidisciplinary team—including, for example, neurosurgeons and craniofacial specialists—plays a crucial role in ongoing care. In addition to active treatment of symptoms, long-term surveillance is an essential part of care to monitor for any emerging complications and to ensure timely interventions.

Outcomes for individuals with craniosynostosis 6 vary depending on the severity and combination of features present. Many affected children benefit from early intervention and multidisciplinary care, which can improve craniofacial appearance and overall development. With current standards of care, many individuals experience stabilization of symptoms over time, although the course of the condition can differ widely from one person to another. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists and genetic counselors for personalized guidance and support.