congenital axonal neuropathy with encephalopathy

Congenital axonal neuropathy with encephalopathy is a very rare condition that primarily affects the motor and sensory nerves as well as the central nervous system. It typically presents at birth or soon afterward with features including generalized muscular hypotonia and distal muscular weakness, accompanied by respiratory and swallowing difficulties. In addition, central nervous system involvement leads to progressive microcephaly, seizures, and global developmental delay, which can affect cognitive and neurological development. Because the condition is very rare, affecting fewer than 1 in a million people, families often face significant diagnostic and management challenges.

The clinical presentation of this condition is marked by both peripheral and central nervous system involvement. Affected infants typically have a reduced muscle tone (hypotonia) and show predominantly distal muscular weakness, which may compromise movement and motor function. Respiratory and swallowing difficulties are common, potentially leading to complications such as aspiration pneumonia. Central nervous system features include progressive microcephaly, seizures, and global developmental delay, indicating challenges in cognitive and neurological development. In addition, variable features such as hearing loss, ocular abnormalities, skeletal anomalies including talipes equinovarus, scoliosis, joint contractures, cryptorchidism, and distinctive facial features (for example, coarse facies and hypertelorism) may be seen. Not all individuals experience all features, and severity varies considerably.

While the precise genetic basis of congenital axonal neuropathy with encephalopathy remains under investigation, the condition is described in the literature as following an autosomal recessive pattern. This means that affected individuals likely inherit two copies of a genetic change—one from each parent—although the specific genes involved have not yet been clearly established. Parents may be asymptomatic carriers, and the risk for recurrence is increased when both parents carry the underlying genetic variant. Given the complexity of the condition’s genetic origins, families are encouraged to seek genetic counseling to discuss inheritance patterns and implications for future family planning.

Currently, management of congenital axonal neuropathy with encephalopathy focuses on supportive care and symptom management, as there are no specific treatments approved for this condition. Treatment is tailored to each individual and usually involves a multidisciplinary team that may include neurologists, pulmonologists, physical and occupational therapists, and nutrition specialists. Supportive interventions may address motor impairments through physical and occupational therapy, assist in managing respiratory and swallowing difficulties, and provide nutritional support. In addition, regular surveillance is an essential part of long-term care, helping to identify complications such as respiratory insufficiency or orthopedic issues at an early stage. Genetic counseling is recommended to guide families through inheritance risks and future planning, and patients should discuss all treatment options with their healthcare team.

The overall prognosis for congenital axonal neuropathy with encephalopathy is variable and depends on the severity of symptoms as well as access to comprehensive, multidisciplinary care. Many affected individuals experience significant challenges, particularly due to respiratory complications and aspiration pneumonia, which may adversely impact the clinical course. However, with current standards of care, some individuals may experience a period of stabilization despite the earlier onset of symptoms. Outcomes described in medical literature continue to evolve as standards of care improve, and it is important to recognize that not all individuals experience the same progression. Families are encouraged to connect with specialists and genetic counselors who can provide guidance and support tailored to each unique situation.

A clinical trial is currently underway exploring new treatment approaches for congenital axonal neuropathy with encephalopathy. Although research in this area is in its early stages, families and patients interested in emerging therapies can search ClinicalTrials.gov or discuss potential trial participation with their care team.