Langer–Giedion syndrome

Overview

Langer–Giedion syndrome, also known as trichorhinophalangeal syndrome type II (TRPS II), is a rare genetic disorder characterized by distinctive facial features, skeletal abnormalities, and multiple benign bony growths called exostoses. First described by Drs. Langer and Giedion, the condition combines features of trichorhinophalangeal syndrome type I and multiple exostoses. Affected individuals often present with short stature, sparse scalp hair, and intellectual disability. The syndrome is congenital and usually identified in early childhood.

Causes

Langer–Giedion syndrome is caused by a deletion on chromosome 8q24.11–q24.13. This chromosomal deletion involves two key genes:

• TRPS1 gene – associated with the trichorhinophalangeal features (hair, nose, and finger bone anomalies).

• EXT1 gene – responsible for the development of multiple exostoses (benign bony growths).

The syndrome is typically not inherited but occurs due to a spontaneous (de novo) chromosomal deletion. In rare cases, it can be inherited in an autosomal dominant pattern.

Symptoms

The clinical features of Langer–Giedion syndrome can vary in severity but commonly include:

• Distinctive facial features – including a long philtrum, bulbous nose, thin upper lip, large ears, and sparse scalp hair.

• Short stature – often evident in early childhood.

• Multiple exostoses – benign bony outgrowths that can affect the movement and alignment of joints.

• Skeletal abnormalities – such as cone-shaped epiphyses of the fingers, hip dysplasia, or scoliosis.

• Loose skin and joint laxity – in some individuals.

• Developmental delays – including mild to moderate intellectual disability in some cases.

Diagnosis

Diagnosis of Langer–Giedion syndrome is based on clinical findings and confirmed by genetic testing. Diagnostic steps include:

• Physical examination – to identify characteristic facial features, skeletal anomalies, and exostoses.

• Radiographic imaging – especially X-rays, to detect exostoses and bone abnormalities.

• Chromosomal microarray analysis – to identify deletions on chromosome 8q24.

• Molecular genetic testing – may be used to detect deletions or mutations in the TRPS1 and EXT1 genes.

Treatment

There is no cure for Langer–Giedion syndrome, and treatment focuses on managing the symptoms and complications. A multidisciplinary approach is often required and may include:

• Orthopedic care – to monitor and treat complications from exostoses, such as nerve compression or joint limitation.

• Physical and occupational therapy – to improve mobility and daily function.

• Speech and developmental therapy – for children with language delays or intellectual disability.

• Surgical removal of exostoses – in cases where they cause pain or interfere with function.

• Genetic counseling – for affected families to understand inheritance and recurrence risks.

Prognosis

The prognosis for individuals with Langer–Giedion syndrome depends on the severity of symptoms and associated complications. Most individuals have a normal life expectancy but may face challenges related to mobility, learning, and joint function. Early intervention and supportive therapies can significantly improve quality of life. Regular follow-up with specialists is important for managing orthopedic and developmental concerns over time.