Jackson–Weiss syndrome

Overview

Jackson–Weiss syndrome is a rare genetic disorder primarily affecting the development of the bones in the skull and feet. Classified as a type of craniosynostosis syndrome, it leads to premature fusion of certain skull bones, resulting in an abnormal head shape. Individuals with this condition often exhibit distinct facial features and foot abnormalities, while the hands and intelligence are usually unaffected. Jackson–Weiss syndrome is part of a broader group of disorders known as craniofacial syndromes.

Causes

The condition is caused by mutations in the FGFR2 gene (fibroblast growth factor receptor 2), located on chromosome 10. This gene plays a crucial role in the development and maintenance of bone and other tissues. Mutations in FGFR2 lead to abnormal signaling that results in early fusion of bones, especially in the skull and feet. Jackson–Weiss syndrome follows an autosomal dominant inheritance pattern, meaning only one copy of the altered gene is sufficient to cause the disorder.

Symptoms

The clinical features of Jackson–Weiss syndrome can vary but typically include:

• Premature fusion of skull bones (craniosynostosis), leading to a misshapen head

• Wide-set eyes (hypertelorism)

• Prominent forehead

• Midface hypoplasia (underdevelopment of the middle facial area)

• Foot anomalies, such as:

  • Broad and deviated great toes

  • Fused or unusually shaped foot bones

  • Short and wide feet

• Normal hand structure and function

• Normal cognitive development in most cases

Diagnosis

Diagnosis of Jackson–Weiss syndrome is based on clinical evaluation, physical examination, and family history. Imaging studies such as X-rays or CT scans can reveal craniosynostosis and foot bone anomalies. Genetic testing confirming a mutation in the FGFR2 gene can provide a definitive diagnosis. Prenatal diagnosis may be possible in families with a known mutation through chorionic villus sampling or amniocentesis.

Treatment

There is no cure for Jackson–Weiss syndrome, but treatment focuses on managing symptoms and improving quality of life. Management strategies may include:

• Surgical intervention to correct skull deformities and relieve intracranial pressure if necessary

• Orthopedic procedures to address foot abnormalities for improved function and mobility

• Regular follow-ups with a multidisciplinary team including craniofacial surgeons, orthopedic specialists, and genetic counselors

• Supportive therapies such as physical therapy or orthotics in cases of impaired gait

Prognosis

The long-term outlook for individuals with Jackson–Weiss syndrome is generally favorable, particularly because intelligence is usually unaffected. Early surgical and supportive interventions can address most of the physical anomalies effectively. Lifespan is typically normal, and many individuals lead independent and productive lives. However, prognosis may vary based on the severity of the cranial and foot abnormalities and access to timely medical care.