ciliary dyskinesia, primary, 47, and lissencephaly

Ciliary dyskinesia, primary, 47, and lissencephaly is a multi-system condition that principally affects brain development and respiratory function. A key feature of the disorder is lissencephaly, a severe brain malformation that often results in cognitive and developmental challenges, while recurrent respiratory infections and respiratory distress are commonly observed. Pathogenic variants in the TP73 gene underlie the condition, which is inherited in an autosomal recessive pattern. Precise prevalence estimates have not been established, and severity as well as the combination of features can vary considerably among affected individuals.

The clinical presentation is defined by a combination of neurological and respiratory features. Lissencephaly is always present and is associated with significant neurological impact that may include cognitive impairment and developmental delays. In addition, nearly all individuals experience recurrent respiratory infections, with many also showing signs of respiratory distress. Seizures, while less common, have been reported in a subset of patients. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the TP73 gene, which plays a role in cellular regulation and development. It is inherited in an autosomal recessive pattern, meaning that an affected individual has received a pathogenic variant from each parent. For families, this implies that there is a 25% chance with each pregnancy for parents who are both carriers to have an affected child. Genetic counseling is recommended to guide families through understanding the inheritance and implications for future pregnancies.

Currently, management focuses on supportive care and symptom control since no treatments are specifically approved for this condition. Care is highly individualized and typically involves a multidisciplinary team that may include neurologists, pulmonologists, and other specialists. Regular surveillance is an essential part of long-term care, helping to identify complications early, and genetic counseling is recommended to assist families in understanding treatment options and inheritance. Patients should discuss treatment options with their healthcare team to determine which therapies may be most appropriate for their specific situation.

The course of the condition is variable, with outcomes differing considerably from one individual to another. The neurological and respiratory challenges may impact quality of life, and while some individuals experience more severe symptoms, others may have a milder clinical course. With current standards of care and ongoing improvements in management strategies, outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to seek guidance from specialists and consider genetic counseling to better understand long-term management options.