ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome

Ataxia-intellectual disability-oculomotor apraxia-cerebellar cysts syndrome, also called Poretti-Boltshauser syndrome, is a neuro-ophthalmological condition that chiefly affects the brain and eyes. It is caused by pathogenic variants in the LAMA1 gene, which encodes laminin alpha-1, a protein important for early brain and retinal development. Signs usually begin in infancy or early childhood, when parents notice balance problems or delayed developmental milestones. The condition is extremely uncommon, affecting fewer than one in one million people worldwide. Both boys and girls can be affected, and the clinical picture is considered nonprogressive in most individuals.

The hallmark feature is nonprogressive cerebellar ataxia, meaning children have difficulty with coordination and balance that tends not to worsen over time. Developmental delays in sitting, walking, and speech are typical, and many individuals have mild to moderate intellectual disability. Eye movement problems such as oculomotor apraxia, strabismus, and occasionally amblyopia or retinal dystrophy contribute to visual challenges. Brain magnetic resonance imaging often reveals cerebellar cysts, dysplasia of the cerebellar cortex, and underdevelopment of the cerebellar vermis, findings that help clinicians recognize the syndrome. Generalized hypotonia (low muscle tone) is reported in a minority of affected children and may improve with therapy. Not all individuals experience all features, and severity varies widely between individuals. Because neurological and cognitive needs can be complex, families frequently engage physical, occupational, speech, and vision specialists as well as special-education services to support optimal development.

This syndrome is inherited in an autosomal recessive pattern. To develop the condition, a child must receive two non-working copies of the LAMA1 gene, one from each parent. Parents who carry one altered copy are typically healthy because their remaining copy provides enough laminin alpha-1 for normal function. The condition may be more common when parents share a common ancestor, because related individuals are more likely to carry the same rare variant. For carrier parents, each pregnancy carries a 25 percent chance of having an affected child, a 50 percent chance of having a carrier child, and a 25 percent chance of having a child who is neither affected nor a carrier. Genetic counseling can help families understand testing options, discuss implications for other relatives, and plan future pregnancies.

Currently, management focuses on supportive care and symptom management. Early and ongoing physical and occupational therapy help children maximize balance and motor skills, while speech and language therapy addresses communication challenges. Regular ophthalmologic care is important to manage strabismus, amblyopia, or significant refractive errors such as myopia, and some children benefit from corrective lenses or patching. Educational plans tailored to each child’s intellectual and cognitive profile, along with assistive technologies, can enhance learning. Because needs often change over time, care is best coordinated through a multidisciplinary team that may include neurology, developmental pediatrics, rehabilitation medicine, and genetics. Patients should discuss treatment options and surveillance strategies with their healthcare team to determine which approaches are most appropriate for their situation.

Most available reports describe the neurological and cognitive features as nonprogressive, so many children maintain the motor and cognitive skills they achieve, although they may continue to experience coordination difficulties and learning challenges throughout life. Outcomes depend on many factors including symptom severity, access to early intervention, and the effectiveness of educational and rehabilitative supports. With attentive care, many individuals participate in school and family activities and live into adulthood. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with neurologists familiar with this condition, engage genetic counseling for family planning, and seek support groups or rare-disease networks for practical resources and community connection.

Clinical trials are underway exploring new treatment approaches for this syndrome. Individuals interested in participating can search ClinicalTrials.gov or consult their care team about eligibility.