Overview

Barber Say syndrome (BSS) is a rare genetic disorder with onset in the neonatal period. Newborns present with abnormal hair growth, thin paper-like skin, and dysmorphic facial structure. However, there is a negligible abnormality in internal organs as compared to external features.^1,2

A mutation in the gene TWIST2 causes this congenital condition, which shows variable symptoms in all ages, from newborns to older people.^2,3 The external disfiguration does not directly impact the cognition or learning ability of the person with BSS.¹ In light of this, a primary focus should be on the psychosocial impact and quality of life after diagnosing BSS.

Healthcare systems often underestimate how facial deformity affects the psychological dynamics of families and individuals. Physicians treat the specific medical conditions associated with BSS . Similarly, surgical procedures such as nasal surgery and laser therapy can be successful in boosting self-confidence and improving quality of life. Reconstructive surgery, in general, enhances an individual’s overall social status and makes them feel connected to society.^1,4

Causes of Barber Say syndrome

The mutation in the TWIST2 gene is responsible for this genetic condition. Gene testing of the family members is necessary to identify the mutation type, whether it is a new or inherited mutation.^5,6

A relatively small number of individuals are affected by this condition. According to one study, there are fewer than 20 previously reported cases of BSS.⁷ The rarity makes it challenging to know the pattern of inheritance. 

Signs and symptoms of Barber Say syndrome

Symptoms begin to appear just after birth and may vary in severity. Also, some of the clinical features are more frequent than others.²

Common signs and symptoms

The BSS-affected individuals exhibit the following:^2,3,6

• Bulbous nose
• Wide nasal bridge
• Generalised hypertrichosis (abnormal hair growth)
• Malformed or absent eyebrows
• Slacky eyelid
• Scanty eyelashes
• Thin and papery skin
• Thin upper lip
• Broad mouth
• Abnormal pinna (outer ear)
• Absence of nipples
• Micropenis with glans foreskin defect 

This condition brings significant anomalies in the external features. However, the brain, heart, and abdomen do not show any major abnormalities. Similarly, motor and cognitive functions are also well preserved.^1,7

People with this genetic condition are not entirely dependent on their families or social care workers because their motor skills are intact, and their intellectual ability is average. Most individuals with BBS can work, attend school, and lead a fulfilling social life.^1,5

Some rare genetic syndromes share the hallmark features of BSS, as well as other clinical features of BSS. These are:^5,9

• Congenital hypertrichosis lanuginosa (CHL)
• Ambras syndrome (AS)
• Ablepharon macrostomia syndrome (AMS)
• Cantu syndrome (CS)

Therefore, diagnosis of BSS is challenging and requires a series of investigations, including gene testing.

Management and treatment for Barber Say syndrome

Diagnosis

Given the rarity of BSS, the diagnosis may take several years, and thehe diagnostic journey of every individual is different due to various presentations at different stages of life.²

Based on the following information, the diagnosis of BSS is made:^2,3,5

• Clinical history
• Physical examination by a team of medical experts (GARD)
• Medical evaluation and routine blood test
• Skin biopsy and imaging
• Gene analysis

Multidisciplinary approach for the management of BSS

Managing patients with BSS requires teamwork, including :^2,3,8

• Primary care workers
• Medical team: Pediatrician, dermatologist, dentist, ophthalmologist (for eye-check), maxillofacial surgeon, pulmonologist
• Genetic counsellor and geneticist

On physical examination, newborns display the specific signs and symptoms of BSS. However, confirmation of BSS requires gene testing, which helps identify the mutation in the TWIST2 gene.^3,5

Treatment and support after the diagnosis

Unfortunately, there are no drugs to cure BSS. Based on the age of presentation and the severity of the illness, treatment approaches vary from person to person. Nonetheless, medical treatment and surgical intervention can help reduce the disabilities and help better adjust to living. The available treatment includes laser therapy for hair removal, cheiloplasty (lip restoration), botox injection, implants, and rhinoplasty (nose restoration).^1,2

Compared with healthy individuals, people with BSS do not have a much shorter life expectancy. Yet, a person needs continuous familial and social support to navigate this tough journey. Besides financial, medical, and educational funding, establishing support groups and organisations to address the psychological and physical aspects of this disease can help bring them to the mainstream.^1,2

With recent medical advancements, there are marked changes in treatment therapy for people with facial deformities. Newer diagnostic tools such as molecular tests and gene sequencing options have helped better understand this genetic disease. Additionally, treatment such as laser therapy for hair removal and other plastic surgeries has immensely helped people with BSS. Such innovative ways to treat individuals with BSS were not available a few decades back.^1,5

In the United Kingdom, the UK Rare Diseases Framework,, outlines the future priorities in tackling rare diseases by helping with early diagnosis, increasing awareness regarding rare diseases, expanding access to specialist care, and better coordination of care.¹⁰

FAQs

How can I prevent Barber Say syndrome?

Prevention of congenital genetic disease is not possible in a newborn child with the mutation of the TWIST2 gene. Fortunately, a timely intervention can prevent the birth of a child with BSS.⁸

Advice to the carrier that may prevent the birth of a child with any rare diseases:¹¹

• Prenatal testing before conceiving
• Avoiding conceiving with a known carrier if possible
• In-vitro fertilisation after embryonic screening

How common is Barber Say syndrome?   

It is one of the rare genetic disorders. There are very few documented cases of BSS worldwide. Globally, it occurs in one out of every 100,000 births.¹²

Who is at risk of Barber Say syndrome?

The person carrying the mutated TWIST2 gene develops BSS.⁵  Besides parental transmission and new mutations of the TWIST2 gene, no other risk factors are known. Unlike other rare genetic diseases, BSS has no associated risk factors, such as smoking, chemical exposure, or infections.¹¹

 No study suggests a higher risk of BSS in a particular sex .^1,5

When should I see a doctor?

A newborn shows distinctive signs and symptoms suggestive of BSS. As a result of BSS’s  characteristic facial features, a doctor suspects abnormality during the birth of a child in a hospital. Despite the diagnosis, people with BSS need periodic visits to the doctor throughout their life to address various medical and surgical concerns related to the condition.^1,2

Summary

Barber Say syndrome is a rare genetic disorder. Like many other rare diseases, the diagnosis and treatment of this congenital condition is a challenging task. It is present at a very early stage of life. The frequently encountered presentations are excess and abnormal hair growth, absence of eyebrows and eyelashes, and loose skin. Severity varies from person to person; therefore, therapy depends on the symptomatic treatment and surgical procedures.

Due to the rarity of this syndrome, sometimes there is a delay in diagnosis and treatment. There are a few congenital disorders with a similar presentation. Therefore, confirmation is made based on gene testing. BSS has an autosomal or dominant mutation of the TWIST2 gene. It can be a de-novo mutation or a mutation inherited from the parents. Therefore, high-risk couples who want to conceive should undergo antenatal gene testing or avoid pregnancy.

Other than diagnosis and treatment, one should understand the role of social care in bringing families with BSS together. The medical team can help treat this congenital disorder’s disease aspect. But, a social support group can help reduce the trauma related to the disease by sharing each other’s survival stories and coping strategies. More research and clinical trials are required to understand this condition better. The government and various stakeholders should work together to find a solution to treating genetic conditions. Also, the online platform for rare disease awareness can be a good initiative for people with BSS and their families.