Barber-Say Syndrome (BSS) is a rare, congenital condition that affects the development of multiple bodily systems, particularly those derived from the ectoderm. This genetic disorder is present from birth and causes a distinct set of physical characteristics, mainly affecting the craniofacial structures and the skin. With only a few dozen cases reported globally, BSS is considered exceptionally rare, occurring in less than one in a million births. This article explores the physical features, the underlying genetic cause, and the strategies for managing this syndrome.
Clinical Characteristics
The defining features of Barber-Say Syndrome are found in the face and skin. A prominent characteristic involves the eyes, where the eyelids may be turned outward (ectropion), exposing the inner surface of the lid. This outward turning, combined with an inability to fully close the eyes (lagophthalmos) or sparse eyelashes, can compromise ocular health and vision.
The facial structure is marked by a wide mouth (macrostomia) and thin lips. The nose typically appears bulbous with a broad bridge and upturned nostrils. Ears are frequently low-set and misshapen, sometimes showing an underdeveloped or narrow external ear canal.
Skin abnormalities are central to the diagnosis, including thin, fragile, and loose skin, referred to as atrophic skin and cutis laxa. This laxity may lead to deep folds and hyper-extensibility. Conversely, many individuals experience excessive hair growth (hypertrichosis), often noticeable on the forehead, neck, and back.
Other features include underdeveloped or absent nipples and mammary glands, delayed tooth eruption, and sometimes a highly arched or cleft palate. Although the syndrome primarily affects external characteristics, internal organs and cognitive function are typically unaffected. Mild hearing loss or developmental delays have occasionally been noted.
Genetic Basis of the Syndrome
Barber-Say Syndrome is caused by a mutation in the TWIST2 gene, which is located on chromosome 2. This gene provides instructions for making a protein that acts as a transcription factor, regulating the activity of other genes.
The TWIST2 protein plays a significant part in embryonic development, particularly in the differentiation of mesenchymal stem cells, which are precursors to connective tissues like bone and cartilage. Mutations disrupt its normal function, leading to developmental issues in the skin, craniofacial structures, and other ectoderm-derived tissues.
The inheritance pattern is typically autosomal dominant, meaning only one copy of the altered TWIST2 gene is needed for the condition. However, in many reported cases, the mutation occurs spontaneously (de novo) during the formation of reproductive cells or early embryonic development. This means the condition often appears in individuals with no family history.
Diagnosis and Supportive Care
Diagnosis begins with a thorough clinical examination recognizing the characteristic facial and skin features. The presence of congenital generalized hypertrichosis, atrophic skin, ectropion, and macrostomia strongly suggests BSS. Due to the syndrome’s rarity, assessment is often performed by a multidisciplinary team, including a geneticist, dermatologist, and craniofacial specialist.
Confirmation is achieved through genetic testing, which involves sequencing the TWIST2 gene to identify the specific mutation. Genetic counseling determines if the mutation is de novo or inherited, clarifying recurrence risks for the family. Testing is also helpful to distinguish BSS from similar conditions involving TWIST2 mutations, such as Ablepharon-Macrostomia Syndrome.
Since BSS is a genetic condition, care is supportive, focusing on managing symptoms and preventing complications. Ophthalmological care is paramount due to the fragility of the eyes caused by ectropion and lagophthalmos, which can lead to corneal damage. Specialized surgeries are often required to correct eyelid defects and provide necessary protection.
Plastic or craniofacial surgery may address functional or cosmetic issues related to facial dysmorphism, such as the wide mouth or cleft palate. Ongoing management involves monitoring for potential issues:
- Hearing loss.
- Delayed tooth eruption.
- Developmental delays.
Physical and occupational therapies may be needed to support overall development and address motor skill challenges.