Franceschetti–Klein syndrome

Overview

Franceschetti–Klein Syndrome, also known as Treacher Collins Syndrome (TCS), is a rare genetic disorder characterized by craniofacial deformities that primarily affect the development of bones and tissues in the face. It was first described by Adolphe Franceschetti and David Klein, and is often referred to by both their names in older literature. TCS affects approximately 1 in 50,000 live births and varies in severity from mild to severe. The syndrome does not typically impact intelligence but can lead to functional impairments related to breathing, hearing, and vision.

Causes

Franceschetti–Klein Syndrome is caused by mutations in one of the following genes:

• TCOF1 (most common)

• POLR1C

• POLR1D

These genes are involved in the development of craniofacial bones and tissues during embryonic growth. The syndrome is inherited in an autosomal dominant manner in most cases, although autosomal recessive inheritance is also seen, particularly with POLR1C mutations. About 60% of cases result from new (de novo) mutations with no family history.

Symptoms

The severity and combination of symptoms can vary widely, but typical features include:

Craniofacial Abnormalities

• Underdeveloped cheekbones (malar hypoplasia)

• Small jaw and chin (micrognathia)

• Downward-slanting palpebral fissures (outer eye corners)

• Coloboma (notch) of the lower eyelids

• Malformed or absent ears (microtia or anotia)

• Conductive hearing loss due to middle ear anomalies

Other Possible Features

• Cleft palate

• Dental malocclusion

• Airway obstruction or breathing difficulties

• Feeding difficulties in infancy

• Normal intelligence in most cases

Diagnosis

Diagnosis of Franceschetti–Klein Syndrome is based on physical characteristics, family history, and genetic testing. Key diagnostic steps include:

• Clinical evaluation: Observation of characteristic facial features and ear abnormalities.

• Genetic testing: Identification of mutations in TCOF1, POLR1C, or POLR1D genes confirms the diagnosis.

• Imaging studies: CT or MRI may be used to assess craniofacial bone structure and middle ear anatomy.

• Hearing tests: Audiometry to evaluate the extent of hearing loss.

• Prenatal testing: Can be offered if a familial mutation is known.

Treatment

There is no cure for Franceschetti–Klein Syndrome, but treatment is multidisciplinary and aimed at addressing individual functional and aesthetic concerns. Common interventions include:

Surgical Management

• Reconstructive facial surgery (e.g., cheekbone, jaw correction)

• Ear reconstruction or prosthetic ears

• Cleft palate repair

• Tracheostomy in severe cases to manage airway obstruction

Supportive Therapies

• Hearing aids or bone-anchored hearing devices

• Speech therapy

• Feeding support in infancy

• Dental and orthodontic care

• Psychological support and counseling

Educational Support

• Early intervention programs

• Special education plans if learning or communication is affected

Prognosis

The prognosis for individuals with Franceschetti–Klein Syndrome is generally good, especially with early and comprehensive intervention. While the condition can cause significant physical challenges, most individuals have a normal lifespan and normal cognitive development. The degree of functional and cosmetic improvement depends on the severity of the malformations and the effectiveness of treatment. With ongoing medical and supportive care, individuals can lead fulfilling and productive lives.