Barber Say Syndrome

What Is It, Causes, Treatment and More

Author: Nikol Natalia Armata MD

Editor: Alyssa Haag, MD

Editor: Emily Miao, MD, PharmD

Editor: Kelsey LaFayette, DNP, ARNP, FNP-C

Illustrator: Abbey Richard, MSc

Modified: Apr 06, 2026

What is Barber Say syndrome?

Barber Say syndrome (BSS) is a congenital condition and rare variant of ectodermal dysplasia, which affects the development of two or more tissues originating from the embryonic ectoderm. The embryonic ectoderm, which is the outermost layer of cells in the developing embryo, gives rise to various structures including the epidermis (i.e., the outer skin layer) and its accessory structures such as hair, nails, and sweat glands; as well as the nervous system and other related organs like the inner ear, melanocytes, and pituitary gland. BSS typically manifests at birth with characteristics such as excessive hair growth, skin thinning and tightening, ectropion (i.e., outwardly turned eyelids), and macrostomia (i.e., larger than average mouth). Nonetheless, a diverse range of presentations has been reported, spanning from mild to more severe cases.

An infographic detailing Barber Say syndrome.

What causes Barber Say syndrome?

Barber Say syndrome is a rare genetic condition, with less than 1 in 1,000,000 births around the world. More specifically, evidence suggests that several instances of Barber Say syndrome are a result of dominant mutations occurring in the TWIST2 gene, which is essential for proper embryonic development and tissue differentiation, especially of the skeletal and cardiac muscle, craniofacial structures, and limbs. It has been observed to be transferred from parent to child through various inheritance patterns, including autosomal dominant and autosomal recessive patterns. However, sporadic cases of new alterations in genes have also been reported in individuals with no family history of the syndrome.

What are the signs and symptoms of Barber Say syndrome?

The presentation of Barber Say syndrome has a wide range of clinical features, with varying degrees of severity observed among affected individuals. A prominent characteristic of this syndrome is the presence of excessive hair growth, known as hypertrichosis, which typically manifests at birth. Skin changes are also very common, including thin and fragile skin. Additionally, many individuals with Barber Say syndrome exhibit ectropion, a condition where the eyelids turn outward, which can lead to eye-related pathologies, such as ulceration of the conjunctiva, infections, or in rare circumstances, loss of vision. Another notable feature is macrostomia, which is a larger than average-sized mouth. Some individuals may also have a high-arched palate, and abnormalities in their fingers and toes, including syndactyly (i.e., two or more fingers or toes are fused together). In some cases, there may be intellectual or developmental disabilities, although the extent of these challenges can vary widely. Dental issues, such as missing teeth or misalignment, and hearing loss may also be present.

How is Barber Say syndrome diagnosed?

Diagnosing Barber Say syndrome typically requires a combination of clinical assessment, medical history analysis, and genetic testing. The diagnostic process includes a detailed examination of physical characteristics and developmental milestones to identify potential indicators of Barber Say syndrome (e.g., excessive hair growth, macrostomia, thin skin). Various genetic testing methods, ranging from chromosomal analysis to advanced molecular techniques (e.g., whole-exome sequencing [WES] or whole-genome sequencing [WGS]) may be employed. These tests aim to pinpoint specific genetic mutations associated with Barber Say syndrome (e.g., TWIST2 gene mutations), serving to both confirm the diagnosis and potentially uncover the underlying genetic origins of the syndrome. In certain cases, diagnostic imaging studies like X-rays, ultrasound examinations, or MRI scans may be utilized to assess structural irregularities (e.g., umbilical hernia, partial syndactyly, narrow ear canal) within affected individuals.

How is Barber Say syndrome treated?

Treatment options for BSS remain limited at this time as no curative treatment has yet been identified. Therefore, the primary focus of treatment is managing the symptoms and providing supportive care to improve the quality of life for affected individuals. Treatment and management typically require a comprehensive and multidisciplinary approach, involving various medical specialists and therapists (e.g., pediatrician, geneticist, neurologist, occupational therapist, psychologist) who work together to address the diverse needs of those with the syndrome.

Early intervention services, including speech therapy, occupational therapy, and physical therapy, play a crucial role in the care of children with BSS. These interventions are designed to help children reach their full developmental potential and enhance their overall functioning. Regular medical check-ups are essential for individuals with Barber Say syndrome to monitor and manage any associated health issues or complications. Hearing and vision assessments are also crucial to address any sensory impairments and provide appropriate interventions.

Genetic counseling is a valuable resource for families affected by Barber Say syndrome as it can provide information about the genetic basis of the condition and discuss the risk of recurrence in future pregnancies.

Additionally, Barber Say syndrome can present significant challenges for patients and their families. Therefore, psychological and emotional support services can be invaluable in helping individuals and families cope with the demands of the syndrome.

What are the most important facts to know about Barber Say syndrome?

Barber Say syndrome (BSS) is a rare ectodermal dysplasia with neonatal onset characterized by generalized hypertrichosis, atrophic skin, ectropion, and macrostomia. BSS is inherited through various patterns or arising spontaneously from gene mutations, particularly a mutation in the TWIST2 gene, crucial for embryonic development. Diagnosis involves clinical assessment, genetic testing, and imaging studies. Although no cure exists, treatment is focused on symptom management, employing a multidisciplinary approach.

Key Takeaways

Definition	Barber Say syndrome (BSS) is a congenital condition and rare variant of ectodermal dysplasia, which affects the development of two or more tissues originating from the embryonic ectoderm.
Embryonic ectoderm	-Outermost layer of cells in the developing embryo -Gives rise to epidermis (+ accessory structures) and nervous system, among others
Cause	-Autosomal dominant / recessive / sporadic mutation in *TWIST2* gene -Less than 1 in 1,000,000 births
Signs and symptoms	-Excessive hair growth (hypertrichosis) -Thin, fragile skin -Ectropion → conjunctiva ulcerations, infections, vision loss -Macrostomia -High-arched palate -Syndactyly -Intellectual or developmental disabilities -Dental issues -Hearing loss
Diagnosis	-Medical history -Clinical examination -Genetic testing (e.g., whole genome sequencing) -Imaging
Treatment	-Symptoms management and supportive care -Multidisciplinary team -Early intervention services: -Speech therapy -Occupational therapy -Physical therapy -Hearing and vision assessments -Genetic counseling -Psychological support for individuals and families

References

Barber-Say syndrome - About the disease. Genetic and Rare Diseases Information Center. February 2023. Accessed September 19, 2023. https://rarediseases.info.nih.gov/diseases/819/barber-say-syndrome.

Haghighinejad H, Rezaei M, Zamani S. Barber say syndrome (a new case report). Indian Dermatology Online Journal. 2019;10(2):158. doi:10.4103/idoj.idoj_68_18

Marchegiani S, Davis T, Tessadori F, et al. Recurrent mutations in the basic domain of TWIST2 cause ablepharon macrostomia and Barber-Say syndromes. The American Journal of Human Genetics. 2015;97(1):99-110. doi:10.1016/j.ajhg.2015.05.017