diencephalic-mesencephalic junction dysplasia syndrome 1

Diencephalic-mesencephalic junction dysplasia syndrome 1 is a neurodevelopmental disorder that predominantly affects brain development and function. It is characterized by several central nervous system abnormalities, including microcephaly, seizures, and developmental delays. Genetic studies have shown that pathogenic variants in the PCDH12 gene underlie this condition, and it is inherited in an autosomal recessive manner, meaning that affected individuals inherit two defective copies of the gene. Precise prevalence estimates are not well established, and current understanding of the condition continues to evolve as more cases are identified and studied.

The clinical features of diencephalic-mesencephalic junction dysplasia syndrome 1 are predominantly centered on the central nervous system. Virtually all affected individuals present with primary microcephaly and a progressive reduction in head size, which is often accompanied by visual impairment. Neurological manifestations include axial hypotonia and dystonia, and a high frequency of seizures is observed – with focal clonic seizures and other seizure types such as tonic seizures, infantile spasms, and hypsarrhythmia reported in a significant proportion of cases. Global developmental delay, reflecting challenges in cognitive and motor skill development, is a consistent finding, and many children also experience intrauterine growth retardation and premature birth. That not all individuals experience all features, and severity varies considerably between affected individuals.

Diencephalic-mesencephalic junction dysplasia syndrome 1 is caused by pathogenic variants in the PCDH12 gene. PCDH12 is believed to encode a protein that plays a critical role in cell adhesion and neural development, processes that are essential for the proper formation and functioning of the brain. The condition is inherited in an autosomal recessive pattern, which means that each parent typically carries one copy of the mutated gene without showing symptoms. When both parents pass on the mutated gene, there is a 25% chance with each pregnancy for the child to be affected. Given the genetic implications, families are encouraged to consider genetic counseling to understand recurrence risks and explore family planning options.

Currently, management of diencephalic-mesencephalic junction dysplasia syndrome 1 focuses on supportive care and symptom management, as there are no treatments that have been specifically approved for this condition. Treatment plans are carefully tailored to each individual and typically involve a multidisciplinary team, which may include neurologists, developmental specialists, physical therapists, and other healthcare professionals. Supportive therapies such as physical and occupational therapy help address motor difficulties, while interventions for seizure control are implemented to manage the diverse seizure types. In addition to managing active symptoms, regular surveillance is an essential part of long-term care to identify potential complications at an early stage. Patients and families benefit from ongoing discussions with their healthcare team about evolving treatment options, and genetic counseling is recommended as part of the overall management strategy.

The prognosis for individuals with diencephalic-mesencephalic junction dysplasia syndrome 1 is highly variable and depends on the severity of symptoms and the timing of diagnosis. With the current standards of care, many individuals benefit from supportive treatments that address both the neurological and developmental components of the condition. Although the disorder involves significant challenges such as seizures, microcephaly, and global developmental delays, outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to engage with multidisciplinary teams and genetic counselors to better understand the potential course of the condition and to explore available support resources. Severity and symptoms vary widely between individuals, and ongoing research and surveillance are essential to optimize long-term outcomes.