Eiken syndrome

Overview

Eiken syndrome is a very rare inherited skeletal dysplasia characterized by severe delays in bone development and abnormal bone modeling, particularly in the hands, feet, and facial bones. First described in a Norwegian family, the condition affects endochondral ossification—the process by which growing cartilage is replaced by bone—leading to unusually shaped and underdeveloped bones. Unlike many skeletal disorders, Eiken syndrome does not significantly affect intellectual development or internal organs, but it does cause notable physical skeletal anomalies and growth delays.

Causes

Eiken syndrome is caused by mutations in the PTHR1 gene (parathyroid hormone 1 receptor), which encodes a receptor that plays a crucial role in regulating bone development and calcium metabolism. The condition follows an autosomal recessive inheritance pattern, meaning a child must inherit two copies of the mutated gene—one from each parent—to be affected. Individuals with only one copy of the mutation are carriers but do not typically show symptoms.

Symptoms

Symptoms of Eiken syndrome are usually present from birth or early infancy and primarily involve the skeletal system. Key clinical features include:

• Delayed ossification: Severely delayed formation of bones, especially in the long bones and spine

• Short stature: Due to impaired skeletal growth

• Abnormal bone shapes: Including irregularly modeled bones in the hands and feet

• Facial anomalies: Flattened midface, underdeveloped jaw (micrognathia), and broad nasal bridge

• Delayed or absent pubertal development: May be observed in adolescence

• No intellectual disability: Cognitive development is typically normal

Diagnosis

Diagnosis of Eiken syndrome is based on clinical features, radiographic imaging, and genetic testing. Steps in the diagnostic process include:

• Physical examination: To evaluate growth patterns, limb deformities, and facial structure

• Radiographic imaging: X-rays show characteristic skeletal anomalies, including short and malformed long bones, delayed ossification centers, and abnormal vertebrae

• Genetic testing: Confirmation through identification of mutations in the PTHR1 gene

• Family history: Assessment of consanguinity or presence of similar skeletal anomalies in relatives

Other skeletal dysplasias (e.g., Blomstrand chondrodysplasia) may be considered in the differential diagnosis, especially as they can also involve PTHR1 mutations but present with different severity and outcomes.

Treatment

There is currently no cure for Eiken syndrome, and treatment is supportive and symptomatic. Management requires a multidisciplinary approach and may involve:

• Orthopedic care: Monitoring and managing bone growth, limb deformities, and joint mobility

• Physical therapy: To maintain muscle strength and flexibility

• Growth monitoring: Regular assessments to track skeletal development and intervene when needed

• Hormonal evaluations: Especially in adolescence, to assess pubertal development and possible endocrine issues

• Genetic counseling: For affected families to understand recurrence risks and carrier status

Prognosis

The long-term outlook for individuals with Eiken syndrome depends on the severity of skeletal involvement. While growth delays and bone deformities may impact mobility and stature, most individuals have normal intellectual development and life expectancy. Regular medical monitoring and supportive therapies can help improve function and quality of life. Because of the rarity of the condition, long-term outcomes are not well documented, but available reports suggest that affected individuals can lead stable lives with appropriate care.