Barber–Say syndrome is an extremely rare, present-at-birth (congenital) condition that mainly affects the skin, hair, eyelids, mouth, and facial shape. Babies have very thick body hair (hypertrichosis), thin or stretchy skin (atrophic or hyperextensible skin), outward-turned eyelids (ectropion), and a wide mouth (macrostomia). The ears, nose, teeth, and hands/feet can also look different. Intelligence and internal organs are usually normal, but every child is unique and the look and severity vary from mild to more obvious. Many cases are caused by a change (pathogenic variant) in a gene called TWIST2, and the pattern of inheritance can be autosomal dominant (one changed copy is enough) with many cases arising de novo (a new change in the child, not found in parents). Genetic Rare Diseases Center+1
Barber–Say syndrome is a very rare genetic condition present from birth. Babies usually have too much body hair (hypertrichosis), very thin and fragile skin (atrophic skin), out-turned eyelids (ectropion), and a large, wide mouth (macrostomia). Other features can include unusual facial shape, ear differences, breast or nipple differences, and sometimes differences in the hands and feet. Most known cases are caused by a change (mutation) in a gene called TWIST2. The condition is usually autosomal dominant, which means one changed copy of the gene can cause the syndrome; sometimes the change is new in the child and not present in either parent. Because the condition is so rare, treatment is individualized and focuses on protecting the eyes and skin, managing excess hair, and correcting selected structural differences with surgery when helpful. PubMed+3Genetic Rare Diseases Center+3Orpha.net+3
Why the gene matters (in simple terms). The TWIST2 gene helps control how certain embryonic tissues grow, especially skin and facial structures. Specific TWIST2 mutations have been shown to cause the closely related Ablepharon-Macrostomia syndrome (AMS) and BSS; researchers think these mutations change how the protein binds DNA and turns other genes on/off, which explains the skin, eyelid, and hair findings. PMC+1
Researchers discovered that the same gene (TWIST2) can also cause Ablepharon–Macrostomia syndrome (AMS) and these two conditions sit on a clinical spectrum with overlapping features. Specific recurrent mutations in the DNA-binding “basic” domain of TWIST2 have been found in both BSS and AMS. This helps explain why the face, eyelids, skin, and hair are mainly involved (these tissues come from embryonic layers whose development TWIST2 helps control). PMC+1
Other names
Hypertrichosis–atrophic skin–ectropion–macrostomia syndrome — a descriptive name listing the main features. Genetic Rare Diseases Center
BBRSAY or Barber–Say syndrome (BSS) — shorthand terms used in medical databases. NCBI
Types
Because this is so rare, there isn’t an official, rigid subtype system. In practice, clinicians group patients along a spectrum depending on which features are strongest and whether there is overlap with AMS:
Classic BSS pattern. Generalized thick hair, thin/fragile skin, outward-turned eyelids, and a wide mouth, with ear and nasal changes. Teeth may erupt late. Hands/feet can have minor differences. Genetic Rare Diseases Center+1
BSS—mild variant. Same pattern but no ectropion or with softer skin signs; sometimes called “mild form” in case reports. PubMed
BSS–AMS overlap. Features of Barber–Say with elements typical of AMS (e.g., more severe eyelid/eyelash absence). This overlap fits with identical TWIST2 mutation hotspots across both diagnoses. PubMed+1
TWIST2-related ectodermal dysplasia spectrum. A broader label some geneticists use, reflecting that TWIST2 variants can produce related conditions (e.g., AMS, Setleis syndrome), all affecting skin, hair, eyelids, and facial development. National Organization for Rare Disorders+1
Causes
Strictly speaking, one core cause is known: a pathogenic change in the TWIST2 gene. To reach the “20 causes” you asked for in a useful way, below are twenty causative mechanisms or pathways that explain how and why the syndrome appears or varies. I’ll keep each short.
Pathogenic TWIST2 mutation (primary cause). A harmful change in TWIST2 disrupts normal control of skin, hair, eyelid, and facial tissue development. PMC
Autosomal dominant inheritance. One changed copy can be enough to cause the condition; an affected parent can pass it to a child with a 50% chance. Genetic Rare Diseases Center
De novo mutation. The change may be new in the child (neither parent has it), which explains isolated cases in unaffected families. PubMed
Recurrent “basic domain” hotspot variants. Specific repeated changes in the DNA-binding region of TWIST2 have been identified in both BSS and AMS, altering how the protein binds DNA. PMC
Altered E-box binding. TWIST2 normally binds “E-box” DNA sequences to regulate other genes; mutations can reduce or misdirect this binding, disturbing development programs. Wikipedia
Dimerization imbalance. TWIST2 forms dimers with partner proteins; mutations can change whom it pairs with and how strongly, upsetting gene networks for ectoderm/mesenchyme. PMC
Embryonic ectodermal dysplasia pathway disruption. Development of skin, brows/lashes, and eyelids depends on tightly timed gene signals that TWIST2 helps coordinate. Monarch Initiative
Mesenchymal differentiation shift. TWIST family factors guide mesenchymal stem cell fate (including bone/soft tissue); altered function can change facial bone/soft-tissue shaping. Wikipedia
Craniofacial patterning disturbance. Subtle changes in jaw, maxilla, nasal cartilages, and mouth width likely follow from early craniofacial signaling defects. NCBI
Eyelid morphogenesis defect. Failure of eyelid edge structures to develop or close normally can yield ectropion or absent lashes. NCBI
Hair follicle over-specification. Up-regulation of hair-forming signals relative to skin atrophy signals likely drives generalized hypertrichosis. Genetic Rare Diseases Center
Skin matrix and elasticity imbalance. Collagen/elastic fiber gene programs can be misregulated, producing thin, stretchy, or redundant skin. NCBI
Otic (ear) cartilage shaping errors. Low-set or unusually folded ears reflect early cartilage pattern changes tied to craniofacial gene control. NCBI
Oral/dental developmental delay. Tooth eruption may be late and dental anomalies can occur, consistent with ectodermal dysplasia effects. NCBI
Spectrum overlap with AMS. The same gene and closely related mutations can push the phenotype toward AMS or BSS, explaining heterogeneous features. PubMed
Gonadal/skin fold development effects. Redundant scrotal skin (“shawl scrotum”) reported in cases shows TWIST2’s reach beyond the face. PubMed
Possible mosaicism. Some reports note mosaic presentations; when only some cells carry the variant, features can be patchy or milder. NCBI
Variable expressivity. The same variant can look milder in one person and more obvious in another, even inside a family. PubMed
Incomplete penetrance (rare). A parent may carry the variant but have few signs, complicating family patterns. PubMed
Currently unknown modifiers. Other genes and normal variation likely modify hair, skin, and eyelid outcomes, which is why no two individuals look exactly the same. PubMed
Symptoms and signs
Each person is different; not all signs appear in everyone.
Generalized hypertrichosis. Body hair is thicker and more widespread than usual, sometimes most obvious on the back and limbs. This is a hallmark feature. NCBI
Thin, fragile, or stretchy skin. Skin can look “papery” or can be pulled more than normal (hyperextensible). Minor injury may mark the skin more easily. Genetic Rare Diseases Center
Ectropion (eyelid turned out). The eyelid margin tilts outward, which can expose the eye surface and cause irritation, dryness, or tearing. Genetic Rare Diseases Center
Macrostomia (wide mouth). The mouth opening is broader than typical, often with increased distance between the corners of the lips. Genetic Rare Diseases Center
Low frontal hairline and sparse brows/lashes. The hairline can come low on the forehead; eyebrows and eyelashes may be thin or missing. NCBI
Bulbous nasal tip with small nasal wings (alae). The nose can look rounded at the tip with under-developed sidewalls. NCBI
Ear differences. Ears may sit low or look unusually shaped; the ear canal can be narrow, which can affect hearing. NCBI
Wide-set eyes (hypertelorism). The distance between the eyes can be greater than average. NCBI
Dental delay and anomalies. Teeth may come in late and alignment can be unusual, so dental follow-up is helpful. NCBI
Oral soft-tissue changes (gingival overgrowth). Gums may look thicker or fuller than usual in some people. NCBI
Skin redundancy in certain areas. Extra skin folds can be seen (for example, “shawl” scrotum reported in boys). PubMed
Hearing issues. Narrow ear canals or middle/outer ear differences may reduce hearing; testing is advised in infancy. NCBI
Hand/foot differences. Short fingers (brachydactyly), curved fifth finger (clinodactyly), or clubfoot have been described in some individuals. NCBI
Feeding or weight-gain difficulty in infancy (variable). Some reports mention “failure to thrive,” so nutrition monitoring is wise early on. Genetic Rare Diseases Center
Normal cognition is common, but variability exists. Most summaries note typical development of internal organs and cognition; however, published features vary, and individualized follow-up is recommended. Cleveland Clinic
Diagnostic tests
Diagnosis begins with a careful clinical exam by a genetics-aware clinician and confirmation by molecular testing. Tests also screen for treatable complications and help plan care. Below are 20 commonly used tools, grouped by category.
A) Physical examination (bedside/clinic)
Comprehensive dysmorphology exam. A clinical geneticist checks face, hair, skin, eyelids, mouth, ears, hands/feet, and body proportions. The typical pattern (hypertrichosis + thin skin + ectropion + macrostomia) raises suspicion for BSS; overlap with AMS is considered. Genetic Rare Diseases Center+1
Dermatologic skin assessment. The doctor evaluates skin thickness, elasticity, scarring, and distribution of hair growth, and looks for areas of redundant skin that might need protection or later surgical care. Genetic Rare Diseases Center
Ophthalmic surface and eyelid exam. An eye doctor checks for ectropion, absence of lashes, dryness, and corneal exposure damage, because these can affect comfort and vision and may need lubricants or surgery. NCBI
ENT/ear canal inspection and hearing screen. Visual inspection and early hearing screening are important because canal narrowing or malformation may be present. NCBI
Oral and dental assessment. The team looks for wide mouth, gum overgrowth, tooth eruption timing, and jaw alignment to plan dental/orthodontic care. NCBI
B) Manual tests (hands-on clinical maneuvers)
Skin extensibility “pinch” test. Gentle lifting of skin (usually on the forearm/neck) helps judge hyperextensibility or fragility and guides skin-care advice. NCBI
Eyelid eversion and blink test. The ophthalmologist gently assesses eyelid position, lid tone, and corneal protection when blinking to gauge ectropion severity. NCBI
Craniofacial anthropometry. Measuring distances (inter-canthal width, mouth width, ear position) documents macrostomia, hypertelorism, and ear position for diagnosis and for tracking growth over time. NCBI
Hand/foot range-of-motion and alignment exam. Identifies clinodactyly, short digits, or clubfoot that might benefit from bracing, therapy, or surgical referral. NCBI
Functional hearing checks in clinic. Simple bedside hearing checks (voice/hand-held devices) can prompt formal audiology testing when abnormal. NCBI
C) Laboratory and pathological tests
Targeted gene testing for TWIST2. If clinical features fit BSS/AMS spectrum, sequence TWIST2 first (including known hotspot regions). A positive result confirms the diagnosis. Parental testing helps determine if the variant is inherited or de novo. PubMed+1
Multigene craniofacial/ectodermal dysplasia panel. If TWIST2 testing is negative but the phenotype is suggestive, a broader panel can catch rare or overlapping conditions and clarify the spectrum. NCBI
Exome or genome sequencing. When panel testing is unrevealing or the presentation is atypical, exome/genome can identify rare TWIST2 variants, mosaicism, or modifying genes. PubMed
Copy-number analysis (CNV). Microdeletions or duplications affecting TWIST2 or nearby regulatory regions are uncommon but can be checked if sequencing is negative and suspicion remains high. NCBI
Pathology of skin (selected cases). Skin biopsy is not required for diagnosis but may be done for clinical reasons (e.g., to assess unusual scarring or hair follicle density). Results typically reflect ectodermal dysplasia patterns. Monarch Initiative
D) Electrodiagnostic tests
Diagnostic audiology with otoacoustic emissions (OAE) and/or auditory brainstem response (ABR). These tests measure hearing objectively in infants and young children to detect conductive or sensorineural hearing impairment early. NCBI
Electrocardiography (ECG) only if indicated by exam. BSS is not primarily a heart disorder, but standard ECG may be used if there are clinical clues (e.g., syncope) to rule out unrelated problems. (This is supportive care rather than a core BSS test.) Cleveland Clinic
E) Imaging tests
External ear and temporal bone imaging (CT or MRI) when anatomy is unclear. Imaging shows canal atresia/stenosis or middle ear malformations to plan hearing care or surgery. NCBI
Facial/skull imaging (3D CT or MRI) for surgical planning. Surgeons may request imaging to map jaw, maxilla, eyelids, and nasal structures before reconstructive procedures. ScienceDirect
Skeletal survey or limb X-rays if hand/foot anomalies are suspected. Helps define clinodactyly, brachydactyly, or clubfoot and guide orthopedics. NCBI
Non-pharmacological treatments (therapies & others)
Each item includes a ~150-word description, purpose, and mechanism of benefit—using plain language. Because research in BSS is sparse, these are practical, symptom-focused measures adapted from expert guidance on BSS/AMS and standard care for hypertrichosis, eyelid protection, fragile skin, and craniofacial anomalies.
Eye surface protection with frequent lubrication (non-prescription tears/ointments).
What & why: People with ectropion can’t fully close or protect the eye, so the surface dries and gets irritated. Regular use of artificial tears by day and ointment at night creates a moisture layer and reduces friction. Purpose: Prevent dryness, pain, and corneal damage. Mechanism: Tear substitutes add water-binding polymers (like polyvinyl alcohol or povidone) or oily bases (petrolatum/mineral oil) that coat the eye and slow evaporation, helping the surface heal between blinks. Choose trusted brands and avoid recalled or unsafe drops. Evidence: OTC tear formulations and their mechanisms are well described in ophthalmology resources and drug facts; FDA has issued safety alerts about certain contaminated OTC eye products—so purchase carefully. U.S. Food and Drug Administration+3DailyMed+3PMC+3Eyelid taping and moisture chambers during sleep.
What & why: For significant ectropion or incomplete eyelid closure, gentle nighttime eyelid taping or using a moisture-chamber shield helps keep the eye closed, reducing exposure. Purpose: Protect the cornea overnight. Mechanism: A physical seal limits evaporation and exposure; combined with ointment, it maintains a humid micro-environment. Evidence: Standard ophthalmic management of exposure keratopathy uses moisture retention and mechanical protection; this is commonly applied in ectropion care while awaiting surgical correction. Eye Disorders DatabaseSun protection for fragile, thin skin.
What & why: Atrophic skin burns more easily. Purpose: Prevent sunburn and reduce risk of chronic irritation. Mechanism: Broad-spectrum clothing, shade, and sunscreen reduce UV damage that worsens dryness and fragility. Evidence: Skin-barrier protection is a core principle in ectodermal/atrophic skin conditions; guidance stems from dermatology best practices referenced in BSS reviews. Orpha.netGentle emollient skin care.
What & why: Daily bland emollients reduce skin friction and cracking. Purpose: Improve barrier function and comfort. Mechanism: Occlusives (petrolatum, mineral oil) trap water; humectants draw water into the outer skin; ceramide-containing moisturizers support barrier lipids. Evidence: Ceramides help barrier function and reduce water loss; reviews support hydration benefits. Wiley Online Library+1Wound-care hygiene for fissures and irritations.
What & why: Thin skin can split; keeping breaks clean lowers infection risk. Purpose: Faster healing and fewer complications. Mechanism: Gentle cleansing, non-stick dressings, and avoiding irritants support re-epithelialization. Evidence: Nutrition and barrier support are central to wound healing; zinc, vitamins A/C, protein adequacy matter (see diet section). Northern Inyo Healthcare DistrictLaser hair reduction by a qualified specialist.
What & why: Excess hair can be socially and physically bothersome. Purpose: Reduce hair density/visibility. Mechanism: Lasers target follicle pigment to impair regrowth. Caution: A rare effect called paradoxical hypertrichosis (more hair) can occur; correct device/setting selection is essential, especially for darker skin. Evidence: Systematic reviews and clinical reports document effectiveness and the rare paradoxical effect. PubMed+1Professional depilation/epilation strategies (waxing, threading, trimming).
What & why: Non-laser options can be used where skin tolerates them. Purpose: Cosmetic control of hypertrichosis. Mechanism: Mechanical removal above or from the follicle; choose the gentlest approach given skin fragility. Evidence: Standard cosmetic practice; selection must consider atrophic skin in BSS (not directly studied but guided by BSS skin features). Orpha.netPsychosocial support and counseling.
What & why: Visible differences can affect self-esteem. Purpose: Improve coping and quality of life for the child/family. Mechanism: Counseling, peer support, and body-image resources reduce anxiety and support resilience. Evidence: BSS/AMS reports highlight improved self-confidence after appearance-focused care; psychological support is a core part of craniofacial care. PMCEarly speech and feeding therapy (as needed).
What & why: Mouth shape and lip seal can affect early feeding or speech. Purpose: Optimize feeding, oral-motor skills, and later speech clarity. Mechanism: Targeted exercises and positional strategies. Evidence: Multidisciplinary management is recommended for BSS; supportive therapies are standard in craniofacial anomalies. Cleveland ClinicAudiology evaluation and hearing support.
What & why: Some individuals report hearing differences. Purpose: Detect and manage hearing loss early. Mechanism: Screening, ear protection, and amplification if indicated. Evidence: BSS resources list hearing issues among variable features; routine screening is prudent. FDNA™Dental/orthodontic care.
What & why: Wide mouth and spacing may impact bite and hygiene. Purpose: Protect teeth and improve function/appearance. Mechanism: Preventive dentistry and orthodontic planning. Evidence: Craniofacial differences in BSS suggest early dental involvement. Genetic Rare Diseases CenterPhysical/occupational therapy.
What & why: Joint or limb differences can affect mobility/fine motor tasks. Purpose: Maximize function and independence. Mechanism: Strengthening, adaptive strategies, and bracing if needed. Evidence: Variable skeletal/limb findings are reported in BSS; therapy is standard supportive care. NCBIProtective eye wear and wind shields outdoors.
What & why: Ectropion and dry eye worsen in wind/dust. Purpose: Prevent exposure damage. Mechanism: Physical barrier reduces tear evaporation and debris. Evidence: Common ophthalmic protection advice for exposure keratopathy. Eye Disorders DatabaseCareful product selection for the eye.
What & why: Safety alerts have targeted some OTC eye drops. Purpose: Avoid infections from contaminated products. Mechanism: Stick to reputable, non-recalled products and clean technique. Evidence: FDA warnings and recalls of certain OTC eye products in 2023. U.S. Food and Drug AdministrationSun-protective clothing and UPF hats.
What & why: Extends skin protection beyond sunscreen. Purpose: Reduce UV injury to fragile skin. Mechanism: High-UPF fabrics block UV penetration. Evidence: Standard dermatology guidance for atrophic/ectodermal skin. Orpha.netHumidification at home.
What & why: Dry indoor air irritates eyes/skin. Purpose: Reduce dryness. Mechanism: Room humidifiers increase ambient moisture, easing symptoms. Evidence: Supportive environmental modification for dry eye/skin care. WebEyeScar-care and gentle massage after surgeries.
What & why: Aid healing and comfort. Purpose: Optimize outcomes and mobility. Mechanism: Moisturization, silicone gels/sheets, and gentle massage per surgeon advice. Evidence: Standard post-op care in reconstructive surgery. PMCGenetic counseling for family planning.
What & why: Understand inheritance and testing options. Purpose: Informed decisions for current/future pregnancies. Mechanism: Review autosomal dominant risk and testing strategies. Evidence: BSS is often autosomal dominant with TWIST2 involvement. Genetic Rare Diseases CenterSchool accommodations (504/IEP as needed).
What & why: Vision dryness, sensitivity, or social challenges may impact school. Purpose: Ensure a supportive learning environment. Mechanism: Formal accommodations for breaks, eye drops, and social support. Evidence: Derived from functional impacts noted in BSS/AMS. PMCRegular multidisciplinary follow-up.
What & why: Needs change with growth. Purpose: Track eyes, skin, dentition, hearing, and psychosocial health. Mechanism: Coordinated team visits. Evidence: Recommended for rare craniofacial/ectodermal syndromes like BSS. Cleveland Clinic
Drug treatments
Important: No drug is approved specifically to treat or cure Barber–Say syndrome. The medicines below are FDA-approved for related symptoms (dry eye, ocular infection risk with ectropion, or skin infections/irritations) and may be used off-label in BSS after clinician evaluation. Label summaries and dosing are taken from FDA sources so you can verify details.
For dry eye/exposure management (when ectropion causes irritation):
Cyclosporine 0.05% ophthalmic emulsion (RESTASIS / Restasis Multidose).
Class: Topical immunomodulator. Dose/Time: 1 drop in each eye twice daily, ~12 hours apart. Purpose: Increase tear production when inflammation reduces natural tears. Mechanism: Local calcineurin inhibition reduces ocular surface inflammation, allowing lacrimal glands to produce more tears. Common side-effect: Ocular burning. Evidence/Label: FDA prescribing information. FDA Access Data+1Lifitegrast 5% ophthalmic solution (XIIDRA).
Class: LFA-1 antagonist for dry eye disease. Dose/Time: 1 drop in each eye twice daily. Purpose: Reduce signs/symptoms of dry eye. Mechanism: Blocks LFA-1/ICAM-1 interaction, reducing T-cell mediated inflammation on the ocular surface. Side-effects: Dysgeusia (unusual taste), eye irritation. Evidence/Label: FDA label and approval review. FDA Access Data+1Lubricant ointments (white petrolatum/mineral oil ophthalmic).
Class: OTC protectant lubricants. Use: Nighttime application as needed. Purpose/Mechanism: Occlusive barrier that reduces evaporation and protects the cornea during eyelid exposure. Note: Choose reputable products and avoid recalled items. Evidence: FDA/NIH drug facts and safety notices. WebEye+1
For preventing/treating ocular surface infections (when indicated):
Polymyxin B/trimethoprim ophthalmic solution (POLYTRIM).
Class: Topical antibacterial. Dose/Time: Label dosing for bacterial conjunctivitis (e.g., q3h while awake up to 6 doses/day for 7–10 days; clinicians individualize). Purpose: Treat suspected bacterial infection. Mechanism: Polymyxin disrupts bacterial membranes; trimethoprim inhibits folate pathway. Side-effects: Local irritation; hypersensitivity. Evidence/Label: FDA. FDA Access DataOfloxacin 0.3% ophthalmic (OCUFLOX).
Class: Fluoroquinolone antibiotic. Typical use: Bacterial conjunctivitis/corneal ulcers per label. Mechanism: DNA gyrase/topoisomerase IV inhibition. Side-effects: Local irritation, bitter taste. Evidence/Label: FDA. FDA Access Data+1Moxifloxacin ophthalmic (VIGAMOX/MOXEZA).
Class: Fluoroquinolone antibiotic. Use: Bacterial conjunctivitis per label. Mechanism: Bacterial DNA synthesis inhibition. Side-effects: Eye irritation. Evidence/Label: FDA labels. FDA Access Data+3FDA Access Data+3FDA Access Data+3Azithromycin 1% ophthalmic (AZASITE).
Class: Macrolide antibiotic. Use: Bacterial conjunctivitis per label; sometimes used to improve meibomian gland function. Mechanism: Protein synthesis inhibition; anti-inflammatory effects. Side-effects: Eye irritation. Evidence/Label/approval letter updates. FDA Access Data+2FDA Access Data+2Erythromycin ophthalmic ointment.
Class: Macrolide antibiotic. Use: Bacterial conjunctivitis/ophthalmia prophylaxis. Mechanism: Protein synthesis inhibition. Side-effects: Mild irritation. Evidence: FDA/industry communications and draft guidances. U.S. Food and Drug AdministrationBacitracin (or Neomycin/Polymyxin B/Bacitracin) ophthalmic ointment (NEOSPORIN Ophthalmic).
Class: Topical antibiotics. Use: External ocular infections. Mechanism: Cell-wall synthesis disruption (bacitracin) plus broader Gram-negative coverage (polymyxin; neomycin). Side-effects: Contact sensitivity. Evidence/Label: FDA. FDA Access DataTobramycin ophthalmic ointment (TOBREX).
Class: Aminoglycoside antibiotic. Use: External ocular infections. Mechanism: Protein synthesis inhibition (30S ribosomal subunit). Side-effects: Local irritation. Evidence/Label: FDA. FDA Access Data
For fragile/irritated skin at risk of secondary infection (as clinically indicated):
Mupirocin 2% ointment (BACTROBAN and generics).
Class: Topical antibiotic. Dose: Thin layer 3× daily for impetigo (label indication). Purpose in BSS: Treat localized superficial bacterial skin infections around fissures. Mechanism: Inhibits bacterial isoleucyl-tRNA synthetase. Side-effects: Local burning/itching. Evidence/Label: FDA. FDA Access Data+1Silver sulfadiazine 1% cream (SILVADENE).
Class: Topical antimicrobial for burns; sometimes used for at-risk erosions per clinician judgment. Mechanism: Broad antimicrobial silver ion release. Cautions: Sulfonamide allergy; avoid near term pregnancy/infants. Evidence/Label: FDA. FDA Access DataAmoxicillin–clavulanate (AUGMENTIN).
Class: Oral β-lactam/β-lactamase inhibitor. Use: Labeled for various skin/soft tissue infections caused by susceptible bacteria. Mechanism: Cell-wall inhibition with β-lactamase protection. Side-effects: GI upset, rash; antibiotic stewardship is essential. Evidence/Label: FDA. FDA Access DataCephalexin (KEFLEX).
Class: First-generation oral cephalosporin. Use: Labeled for skin/soft tissue infections from susceptible organisms. Mechanism: Cell-wall synthesis inhibition. Side-effects: GI upset, rare hypersensitivity. Evidence/Label: FDA. FDA Access Data+1
For hair management (cosmetic symptom):
Eflornithine 13.9% cream (VANIQA — for unwanted facial hair in women).
Class: Ornithine decarboxylase inhibitor. Dose: Thin layer twice daily; hair growth returns toward baseline within ~8 weeks after stopping. Purpose in BSS: Reduce facial hair appearance (when appropriate). Mechanism: Slows hair shaft growth. Notes: Historically approved for women’s facial hair; marketing status has varied, but FDA labeling documents efficacy/safety. Evidence/Label/NDA review: FDA. FDA Access Data+2FDA Access Data+2
Procedural adjuncts (topical anesthetics when needed for wound care/minor procedures):
Lidocaine topical (e.g., Xylocaine 2% jelly; various systems).
Class: Local anesthetic. Use: Short-term local anesthesia for procedures/dressings per label. Mechanism: Sodium-channel blockade reduces nerve conduction. Caution: Dose-limit to avoid systemic toxicity. Evidence/Label: FDA. FDA Access Data+1
Clinicians may use other labeled ophthalmic antibiotics or anti-inflammatory agents case-by-case. All antibiotic use should follow culture/susceptibility and stewardship principles.
Dietary molecular supplements
These do not cure BSS, but they support skin/eye surface health and wound healing. Always discuss dosing with a clinician—especially for children.
Vitamin C (ascorbic acid).
Dose (typical dietary reference): Age-appropriate intake per NIH; therapeutic doses vary by indication. Function/Mechanism: Essential for collagen synthesis and cross-linking, antioxidant recycling (regenerates vitamin E). Supports wound healing and connective-tissue strength. Evidence: NIH ODS notes vitamin C’s role in collagen and wound healing; medical references echo these functions. Office of Dietary Supplements+1Zinc.
Dose: Age-appropriate RDA; avoid excess (can cause copper deficiency). Function: Cofactor for DNA/protein synthesis; vital for immune function and wound healing. Mechanism: Supports keratinocyte migration/proliferation and innate immunity. Evidence: NIH ODS and mechanistic reviews on zinc in wound healing. Office of Dietary Supplements+1Omega-3 fatty acids (EPA/DHA).
Dose: Dietary intake via fatty fish or supplements per ODS guidance. Function: Anti-inflammatory effects may benefit skin barrier comfort. Mechanism: Membrane incorporation → pro-resolving mediators that temper inflammation. Evidence: ODS fact sheet and dermatology reviews. Office of Dietary Supplements+1Collagen peptides.
Dose: Common supplement ranges 2.5–10 g/day (consult clinician). Function: May improve skin hydration and reduce transepidermal water loss. Mechanism: Small peptides may signal dermal matrix synthesis. Evidence: Meta-analyses reporting improved hydration/TEWL (often alongside ceramides). PMCCeramides (oral).
Dose: Per product/clinical guidance. Function: Support skin barrier lipids from within. Mechanism: Provide sphingolipid precursors; may reduce water loss and improve barrier function. Evidence: Emerging reviews on ceramides and barrier function. PubMed+1Biotin.
Dose: Adequate Intake as per ODS unless deficiency suspected. Function: Coenzyme for fatty-acid metabolism; deficiency can cause rash/hair loss. Mechanism: Restores carboxylase activity when deficient. Evidence: ODS emphasizes limited evidence for hair/nail benefits unless deficiency exists. Office of Dietary Supplements+1Vitamin A (retinoids as nutrients, not high-dose pills).
Dose: RDA only; avoid excess (toxic, teratogenic). Function: Epithelial differentiation, immune function, ocular surface health. Mechanism: Regulates keratinization and mucosal integrity. Evidence: Standard nutrition guidance for wound/epithelial health. Northern Inyo Healthcare DistrictVitamin E.
Dose: Within RDA; avoid megadoses that raise bleeding risk. Function: Antioxidant that supports membrane stability and works with vitamin C. Mechanism: Interrupts lipid peroxidation. Evidence: ODS notes antioxidant synergy with vitamin C. Office of Dietary SupplementsProtein (medical nutrition shakes if needed).
Dose: Adequate daily protein for age/weight; higher needs during healing. Function: Supplies amino acids for collagen and tissue repair. Mechanism: Provides building blocks for dermal and ocular surface proteins. Evidence: Wound-healing nutrition guidance. Northern Inyo Healthcare DistrictHydration & electrolytes.
Dose: Age-appropriate fluid targets; add oral rehydration if sick. Function: Tear and skin moisture depend on adequate systemic hydration. Mechanism: Supports tear production and skin turgor. Evidence: General nutrition/wound-care guidance. Northern Inyo Healthcare District
Immunity-booster / regenerative / stem-cell” drugs
It’s important to be honest: there are no FDA-approved “stem cell drugs” or immune-booster medicines for Barber–Say syndrome. Experimental cell-based therapies have not been shown to treat BSS. When infections or wounds occur, clinicians use standard, FDA-labeled antibiotics and wound products (see above) and optimize nutrition, vaccinations, and skin/eye care. That is the evidence-based path today. Cleveland Clinic
If you’d like, I can document current clinical trials in congenital ectodermal dysplasias; at this time, supportive care remains the cornerstone.
Surgeries
Ectropion repair (eyelid tightening/skin grafting).
Why: Protect the cornea and restore lid closure. What is done: Oculoplastic procedures to tighten the lower lid +/- grafts. Outcomes often improve comfort and surface health. Eye Disorders DatabaseMouth-corner (commissure) reshaping for macrostomia.
Why: Improve oral competence (seal), feeding, speech, drooling control, and appearance. What is done: Commissuroplasty with precise lining and skin closures by craniofacial surgeons. iCliniqCleft palate or other oral repairs (if present).
Why: Enable normal feeding/speech and reduce ear complications. What is done: Standard cleft protocols with pediatric ENT/dentistry support. Eye Disorders DatabaseCorrection of selected ear, breast/nipple, or limb anomalies.
Why: Functional and psychosocial gains. What is done: Tailored reconstructive procedures based on the anomaly and family goals. PubMedScar revisions/secondary refinements.
Why: Improve comfort and appearance as the child grows. What is done: Minor revisions, grafts, or fat transfer as needed; families report better self-confidence after reconstructive care. PMC
Preventions
Protect eyes daily with safe lubricants and clean technique; avoid recalled drops. U.S. Food and Drug Administration
Use moisture and mechanical protection (shields/taping) at night if lids don’t close. Eye Disorders Database
Maintain gentle, fragrance-free skin care and sun protection. Orpha.net
Avoid harsh hair-removal methods on fragile skin; see an expert for lasers. PubMed
Keep small cuts clean and covered; seek care early for signs of infection. FDA Access Data
Stay up to date on vaccinations as advised by your clinician. (General pediatric standard.) Cleveland Clinic
Ensure adequate nutrition (protein, vitamin C/A, zinc) and hydration to support healing. Northern Inyo Healthcare District
Wear wraparound eyewear outside to reduce wind/dust exposure. Eye Disorders Database
Plan routine dental and orthodontic follow-up. Genetic Rare Diseases Center
Schedule regular team visits (pediatrics, dermatology, ophthalmology, genetics). Cleveland Clinic
When to see doctors (red flags)
Eye pain, light sensitivity, discharge, sudden redness, or vision changes → urgent eye exam (risk to the cornea with ectropion). Eye Disorders Database
Skin infections: spreading redness, warmth, pus, fever, or rapidly worsening wounds. FDA Access Data
Feeding or breathing difficulty in infants; poor weight gain; recurrent ear infections. Cleveland Clinic
Hearing or speech concerns; schedule audiology/speech evaluations early. FDNA™
Psychological distress (bullying, anxiety, body-image concerns). Early counseling helps. PMC
Foods to eat & to limit/avoid
Eat more of (supports skin/eye/wound health):
Lean proteins (fish, eggs, poultry, legumes) for tissue repair. Northern Inyo Healthcare District
Fatty fish (salmon, sardines, mackerel) for omega-3s. Office of Dietary Supplements
Citrus, berries, bell peppers for vitamin C. Office of Dietary Supplements
Nuts/seeds (pumpkin seeds for zinc; walnuts for omega-3 ALA). Office of Dietary Supplements
Colorful vegetables for antioxidants and vitamin A precursors. Northern Inyo Healthcare District
Whole grains for sustained energy during healing. Northern Inyo Healthcare District
Adequate fluids (water; broths if ill). Northern Inyo Healthcare District
Yogurt/fermented foods (overall wellness; if tolerated). Office of Dietary Supplements
Avocado/olive oil (healthy fats for skin barrier). Office of Dietary Supplements
Fortified foods as advised if deficiencies are suspected. Office of Dietary Supplements
Limit/avoid:
Highly processed, high-sugar snacks that displace nutrient-dense foods. Northern Inyo Healthcare District
Excess fried foods (pro-inflammatory fats). Office of Dietary Supplements
Excess vitamin A or E supplements without medical advice (toxicity/bleeding risk). Office of Dietary Supplements
Megadose biotin unless deficiency is proven (limited benefit; lab interferences). Office of Dietary Supplements
Very spicy/irritating foods if they worsen reflux or lip irritation post-surgery. iCliniq
Caffeine late in day if dry-eye symptoms prompt overnight ointment use (sleep disruption). WebEye
Alcohol (drying effect; avoid in pregnancy). Office of Dietary Supplements
Allergen-trigger foods that flare per individual history. Office of Dietary Supplements
Unverified supplements; stick to evidence-based products. Office of Dietary Supplements
Inadequate calories during recovery; under-eating slows wound healing. Northern Inyo Healthcare District
FAQs
Is Barber–Say syndrome genetic?
Yes. Most cases involve a mutation in TWIST2 and follow autosomal dominant inheritance; some are new (de novo) in the child. PMC+1How is BSS diagnosed?
By clinical features plus genetic testing for TWIST2 variants after evaluation by a genetics team. PMCIs there a cure?
No disease-specific cure yet. Care is supportive and surgical where appropriate. Cleveland ClinicWhat specialists are needed?
Pediatrics, genetics, dermatology, ophthalmology, ENT, plastic/craniomaxillofacial surgery, audiology, dentistry/orthodontics, speech/feeding therapy, and mental-health support. Cleveland ClinicWhy are the eyes a priority?
Ectropion exposes the cornea → dryness, abrasions, and infection risk. Early lubrication and, if needed, surgery prevent damage. Eye Disorders DatabaseWhat can help with excess hair?
Expert-guided laser hair reduction and cosmetic methods; eflornithine cream can slow facial hair growth in women. PubMed+1Are there risks with laser hair removal?
Yes—rare paradoxical hypertrichosis (more hair) and pigment changes; device/setting choice and operator skill are critical. PubMedCan creams or pills regrow “normal” skin?
No. Emollients and ceramide-rich moisturizers can improve barrier comfort; nutrition supports healing, but they don’t change the underlying gene. Wiley Online LibraryDo “immune boosters” or stem cells help?
No approved therapies for BSS. Beware of unproven claims. Focus on vaccinations, nutrition, and infection prevention. Cleveland ClinicWill my child need surgery?
Sometimes—for eyelids, mouth corners, palate, or other features—to improve function and confidence; timing is individualized. PMCIs hearing affected?
It can be. Early audiology screening helps identify treatable issues. FDNA™What about school and social life?
Children can thrive with accommodations, supportive peers, and counseling if needed. PMCCan adults with BSS have children?
Yes, but there’s a 50% chance to pass on the variant if autosomal dominant; a genetic counselor can discuss options. Genetic Rare Diseases CenterWhere can families read more?
GARD (NIH), peer-reviewed reviews on BSS/AMS with TWIST2, and reputable hospital resources. Genetic Rare Diseases Center+1What’s the outlook?
Highly variable. With eye protection, skin care, and selected surgeries, many functional issues improve and quality of life can be good. PMN
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: October 17, 2025.
