Setleis syndrome

Overview

Setleis syndrome is a rare genetic disorder classified under the group of ectodermal dysplasias—conditions affecting the development of the skin, hair, nails, teeth, and facial structures. It is also sometimes referred to as "focal facial dermal dysplasia type III." The most distinguishing feature of Setleis syndrome is the presence of deep, scar-like depressions or skin lesions on the temples, which resemble healed forceps marks. These facial characteristics are typically present at birth. While the syndrome primarily affects the face, it may also involve other ectodermal tissues, including sparse hair and abnormal eyelashes or eyebrows. Intellectual development is usually normal.

Causes

Setleis syndrome is caused by mutations in the TWIST2 gene, which provides instructions for producing a protein involved in the regulation of gene expression during early embryonic development. TWIST2 plays a critical role in the formation of facial structures and other ectoderm-derived tissues. The syndrome is inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of the mutated gene—one from each parent—to develop the condition. Carriers of a single mutated gene usually do not show any symptoms.

Symptoms

The clinical presentation of Setleis syndrome is most notable in the face and skin. Key signs and symptoms include:

Facial Features:

• Deep, circular or oval skin depressions on both temples (most characteristic feature)

• Coarse facial appearance

• Flattened or broad nasal bridge

• Full cheeks and prominent forehead

Hair and Eyelashes:

• Sparse or absent scalp hair, especially in the frontotemporal regions

• Double rows of upper eyelashes (distichiasis) in some cases

• Absent or sparse eyebrows and lower eyelashes

Other Features (less common):

• Dental anomalies such as delayed eruption or abnormal tooth shape

• Abnormal sweating or heat intolerance (infrequent)

Unlike many other ectodermal dysplasias, Setleis syndrome typically does not affect nail development or significantly impair sweat gland function. Intelligence and internal organ function are generally normal.

Diagnosis

Diagnosis of Setleis syndrome is usually based on the recognition of characteristic facial features, particularly the unique temple lesions present at birth. Key diagnostic steps include:

• Clinical evaluation: Detailed physical examination focusing on facial morphology and ectodermal features

• Family history: Identification of consanguinity or similar features in siblings may support a genetic diagnosis

• Genetic testing: Molecular analysis confirming mutations in the TWIST2 gene is definitive for diagnosis

• Dermatologic consultation: May assist in ruling out other causes of skin lesions or scarring

Differential diagnoses include other facial dysmorphic syndromes and forms of ectodermal dysplasia, such as Goltz syndrome or focal facial dermal dysplasia types I and II.

Treatment

There is no specific cure for Setleis syndrome. Management is supportive and aims to address the cosmetic and psychological aspects of the condition. Common treatment approaches include:

Dermatologic and Cosmetic Care:

• Topical treatments or minor dermatologic procedures for improving skin appearance

• Consultation with a plastic surgeon for severe or cosmetically concerning lesions

Ophthalmologic Management:

• Monitoring and treatment of eyelash abnormalities such as distichiasis, which may irritate the eyes

• Lubricating eye drops if eyelashes cause corneal irritation

Dental and Hair Management:

• Routine dental care and possible orthodontic evaluation if dental anomalies are present

• Wigs or cosmetic scalp treatments for patients concerned about hair thinning or loss

Psychosocial Support:

• Counseling or therapy for self-esteem and body image, especially during adolescence

• Genetic counseling for affected families and prospective parents

Prognosis

The prognosis for individuals with Setleis syndrome is generally excellent in terms of physical health and life expectancy. The syndrome does not usually impact cognitive development or major organ systems. However, the visible facial and hair abnormalities can lead to psychosocial challenges, particularly during childhood and adolescence. With supportive treatment and cosmetic options, most individuals can lead healthy and fulfilling lives.

As a rare condition, ongoing research and awareness are important for improving early diagnosis, expanding treatment options, and supporting affected families through genetic counseling and education.