arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome

Arthrogryposis-oculomotor limitation-electroretinal anomalies syndrome, also called distal arthrogryposis type 5 (DA5), is a developmental condition that primarily affects the muscles, joints, eyes, and breathing mechanics. It is caused by pathogenic variants in the PIEZO2 gene, which encodes a protein involved in sensing mechanical stretch within muscles and other tissues. Symptoms are present from birth, but intellectual development is typically normal. Precise prevalence figures are not available, and only a limited number of families have been described in the medical literature. Severity and symptoms vary widely between individuals, even within the same family.

The hallmark of DA5 is congenital contractures of the hands, feet, and wrists, known as distal arthrogryposis. Newborns often show reduced palm creases, limited wrist extension, and finger flexion contractures that restrict hand movement. Many infants also have clubfoot or other foot positioning issues. Ocular findings are equally characteristic. Almost all affected individuals have drooping eyelids (ptosis) and difficulty moving the eyes outward or upward (external ophthalmoplegia). Some develop strabismus or Duane anomaly, and farsightedness (hypermetropia) is common. Over time, some people are found to have electroretinal changes such as retinal folds, although vision is often only mildly affected. Respiratory and musculoskeletal features emerge or become more apparent with growth. Exercise intolerance, exertional shortness of breath, and a restrictive ventilatory pattern on pulmonary testing reflect reduced chest wall flexibility. Spinal curvature, including kyphosis and scoliosis, may require orthopedic attention. Short stature, high-arched palate, and decreased facial expression add to the recognizable facial profile. Additional features reported in some but not all individuals include blepharophimosis, hypertonia, and recurrent patellar dislocation. Not all individuals experience all features, and the clinical spectrum ranges from mild joint stiffness to more complex multi-system involvement.

DA5 is inherited in an autosomal dominant pattern. A single altered copy of the PIEZO2 gene is sufficient to cause the condition, so each child of an affected individual has a 50 percent chance of inheriting the variant. PIEZO2 encodes a mechanosensitive ion channel that helps convert physical stretch into cellular signals important for muscle tone, joint positioning, and eye movement. Disruption of this channel impairs normal development of joints and extraocular muscles, leading to the combination of contractures and eye movement limitation. Even within the same family, the severity and specific symptoms can vary considerably (variable expressivity). Genetic counseling is recommended for affected individuals and their relatives who are planning a family.

Currently, management focuses on supportive care and symptom management. Early orthopedic intervention, including stretching programs, splinting, and when necessary corrective surgery, aims to maximize joint range of motion and function. Physical and occupational therapy help children gain and maintain mobility and fine-motor skills. Eye-related complications may require evaluation by an ophthalmologist; treatments can include ptosis repair or strabismus surgery to improve visual fields and alignment. Respiratory specialists monitor for restrictive lung disease, and some individuals benefit from breathing exercises or assistive ventilation during sleep. Because multiple organ systems can be affected, ongoing care is best coordinated by a multidisciplinary team familiar with neuromuscular, orthopedic, ophthalmologic, and pulmonary aspects of the condition. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Monitoring typically includes periodic orthopedic assessments for evolving spinal curvature, ophthalmologic examinations to track eye movement and retinal health, and pulmonary function tests to assess breathing capacity. Genetic counseling should be offered to families to discuss inheritance, family planning, and potential reproductive options.

Most individuals with DA5 have a stable course once contractures are addressed and respiratory status is monitored, and many lead active lives with appropriate orthopedic and ophthalmologic care. Outcomes depend on the severity of joint involvement, effectiveness of early interventions, and access to ongoing specialist monitoring. While respiratory restriction can limit endurance, proactive pulmonary care often allows good day-to-day function. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialist centers and genetic counselors for updated guidance and support.