Hypertrichosis-atrophic skin-ectropion-macrostomia syndrome (usually called Barber–Say syndrome) is a very rare genetic condition that affects the outer body tissues that come from the ectoderm (skin, hair, eyelashes/eyelids, and some facial structures). Babies are usually born with very thick or excessive body hair, thin, fragile, or “papery” skin, eyelids that turn outward, and a wide mouth. Other facial findings can include a low hairline, changes in the nose and ears, and widened spacing between the eyes. Intelligence is usually normal, but appearance-related and eye-surface problems may need care. Most known families show an autosomal-dominant pattern (a single gene change can cause the condition), and many cases arise de novo (new in the child). Genetic testing often finds a small change in the TWIST2 gene. orpha.net+2rarediseases.info.nih.gov+2
Barber–Say syndrome is a very rare condition present from birth. Children usually have extra hair all over the body (hypertrichosis), thin and fragile “paper-like” skin (atrophic skin), eyelids that turn outward (ectropion), and a mouth that is wider than usual (macrostomia). It is an ectodermal dysplasia, meaning it mainly affects tissues that come from the body’s outer layer (skin, hair, eyes). Some cases are caused by changes in a gene called TWIST2 and can be inherited in an autosomal dominant way, though new (“de novo”) changes can also happen. Severity varies a lot—even within the same family. Diagnosis is made by the look and pattern of findings, and can be confirmed with genetic testing for TWIST2 variants. There is no single cure; treatment is supportive and tailored to each feature. orpha.net+2rarediseases.info.nih.gov+2
Hypertrichosis means thick, increased hair growth in places where hair is normally present (but now dense) or in unusual areas. In BSS, this may be generalized. It can lead to social distress, skin irritation, and trouble keeping clean or cool. Management uses trimming, depilatories, or—when age, skin type, and safety allow—light/laser hair reduction; expectations must be realistic, and side effects must be discussed carefully. orpha.net+1
Other names
Barber–Say syndrome (BSS)
Hypertrichosis–atrophic skin–ectropion–macrostomia syndrome (descriptive name)
Ectodermal dysplasia with generalized hypertrichosis and macrostomia (descriptive)
(Historically and in differential context) Allelic to Ablepharon-Macrostomia syndrome (AMS) — they share TWIST2 changes but differ in features; AMS has much more severe eyelid underdevelopment (ablepharon). disorders.eyes.arizona.edu+1
Types
Because cases are so rare, doctors don’t split the condition into strict subtypes. Instead, they describe a clinical spectrum:
Classic Barber–Say pattern – the typical four features (hypertrichosis, atrophic skin, ectropion, macrostomia), plus variable facial changes. orpha.net
Mild/attenuated presentations – the key features are present but less marked; may be recognized later. rarediseases.info.nih.gov
Overlap/allelic presentations – features that partly resemble AMS (for example, prominent eyelid problems), reflecting that both disorders are caused by TWIST2 changes in the same protein region. PMC+1
Familial vs. de novo – some families show multiple affected members (autosomal-dominant transmission), while other cases appear for the first time in a child (de novo). PubMed
Causes
Important note: For this syndrome, the single fundamental cause is a pathogenic variant in the TWIST2 gene that disrupts normal embryonic development of ectoderm-derived tissues. The items below unpack ways that cause shows up, mechanisms, and contexts that explain why the features vary from person to person.
TWIST2 missense variants in the basic (DNA-binding) domain – repeatedly found in affected people; these specific changes alter how the protein binds DNA. PMC+1
Dominant-negative effects – the altered TWIST2 protein can interfere with the normal copy, worsening the impact. Wiley Online Library
Gain-of-function effects – some variants make TWIST2 over-active in the wrong way or place. Wiley Online Library
De novo variants – a brand-new change happens in the egg or sperm or early embryo; neither parent is affected. PubMed
Autosomal-dominant inheritance – one altered copy is enough to cause disease; can pass from an affected parent. rarediseases.info.nih.gov
Allelic heterogeneity – different TWIST2 changes can cause a similar BSS picture. PMC
Genotype–phenotype correlation – changes clustered in the basic domain tend to produce BSS/AMS spectrum features. PMC
Modifier genes – other genes may tune severity (suggested by variable features within families). Inference based on variability in case series. PubMed
Epigenetic influences – small differences in gene regulation during development may change how features look. General developmental biology principle; used to explain variability. PMC
Stochastic (random) developmental variation – tiny chance events in early development can shift outcomes, especially in rare syndromes. General principle; invoked to explain intrafamilial variability. PubMed
Tissue-specific sensitivity – eyelid, skin, and hair follicles depend heavily on TWIST2 pathways, so they are most affected. PMC
Overlap with AMS – certain TWIST2 substitutions push the phenotype toward AMS-like eyelid severity. disorders.eyes.arizona.edu
Parental mosaicism (rare) – an apparently unaffected parent may carry the variant in a fraction of egg/sperm cells, explaining recurrence. General genetics concept applicable to autosomal-dominant disorders with de novo variants.
Variable expressivity – same variant, different look in different people. PubMed
Reduced penetrance (uncommon) – a carrier might show very mild signs or be overlooked. General AD genetics concept; compatible with sparse family data.
Misclassification in early reports – some historical cases were re-assigned after better photos/genetics, reflecting evolving diagnosis rather than different biology. PubMed
Environmental/medical modifiers – eye surface dryness, infections, or sun exposure can worsen visible features but are not root causes. (Supportive/clinical observation.)
Nutritional status – poor nutrition can make fragile skin look worse (not causal to the syndrome). (Clinical principle.)
Surgical scarring effects – necessary eye or facial surgeries can change later appearance; again, not causal to the syndrome. (Clinical principle.)
Diagnostic delays – late recognition doesn’t cause the syndrome, but it can allow preventable surface complications (like corneal irritation) to accumulate. (Clinical principle consistent with ectropion care.)
Symptoms and signs
Generalized hypertrichosis – unusual, thick body hair, often striking on the back and limbs, present from birth or early infancy. NCBI
Atrophic, “papery,” fragile skin – skin looks thin and easily damaged; healing may be slower. orpha.net
Ectropion – the lower eyelids turn outward, exposing the inner surface, causing dryness, irritation, and risk to the cornea. orpha.net
Macrostomia – the mouth opening is wider than usual, changing facial proportions and, occasionally, feeding/speech dynamics. orpha.net
Low frontal hairline – the hairline can sit unusually low on the forehead. NCBI
Ear anomalies – ears may be low-set or shaped differently; hearing is usually normal. NCBI
Nasal changes – a bulbous tip or small, under-developed side walls (alae). NCBI
Ocular telecanthus – increased inner-eye corner distance that changes facial spacing. NCBI
Redundant or lax skin folds – some infants have loose skin that can make wrinkles or folds. NCBI
Hypoplastic or absent nipples (variable) – described in several case reports. PMC
Cleft palate (occasional) – not in every child, but reported; may affect feeding/speech and need repair. PMC
Ocular surface symptoms – tearing, dryness, light sensitivity, or recurrent irritation from ectropion exposure. orpha.net
Umbilical or inguinal hernia (occasional) – soft tissue support can be weak, allowing hernias. (Case-level reports.) PMC
Normal cognition in most – developmental delay is not a core feature in well-documented BSS, though appearance issues can impact psychosocial wellbeing. PubMed
Psychosocial impact – visible differences (hair, eyelids, mouth shape) can affect self-image and social interaction; counseling/support help many families. (Clinical principle consistent with rare visible conditions.)
Diagnostic tests
A. Physical examination (bedside assessment)
Full newborn/child exam – confirms the “big four” signs (hypertrichosis, thin skin, ectropion, macrostomia) and looks for other ectodermal changes (hairline, ears, nose). This is the foundation of diagnosis. orpha.net
Dermatologic skin assessment – evaluates fragility, atrophy, healing, and areas at risk of breakdown or infection; guides skincare plans. orpha.net
Ophthalmologic surface exam with fluorescein staining – checks for exposure keratopathy (corneal drying or abrasions) from ectropion; early care prevents damage. (Standard eye care for ectropion.)
Craniofacial/oral exam – measures mouth width, looks for cleft palate or dental alignment issues that may need specialty care. (Craniofacial practice.)
Growth and development check – most have normal cognition; tracking growth and milestones ensures nothing else is missed. PubMed
Family exam – looks for subtle features in parents/siblings that might indicate autosomal-dominant inheritance or mosaicism. PubMed
B. Manual (clinical) tests and measurements
Eyelid laxity and snap-back test – simple lid maneuver to grade ectropion severity and plan lubricants/taping/surgery. (Oculoplastic practice.)
Schirmer tear test – measures tear production to protect the cornea in children with ectropion. (Ophthalmology standard.)
Hair pull/shaft inspection – characterizes hair density and shaft caliber; documents baseline hypertrichosis for follow-up. (Dermatology practice.)
Skin pinch/elasticity assessment – bedside check of skin atrophy and laxity that informs daily care and wound risk. (Dermatology practice.)
C. Laboratory and pathological testing
Targeted genetic testing of TWIST2 (Sanger or NGS panel) – the key confirmatory test; looks for pathogenic variants in the basic DNA-binding domain. A positive result clinches diagnosis and supports counseling. PMC+1
Broader craniofacial/ectodermal dysplasia gene panel – used when features are suggestive but TWIST2 is negative, to check for other rare conditions. (Genomic testing practice; differential diagnosis.)
Chromosomal microarray or exome sequencing – considered when the picture is unclear or broader anomalies exist; increases the chance of finding a genetic answer in rare syndromes. (Clinical genetics practice.)
Skin biopsy (selective) – rarely required; when done, documents dermal atrophy or other changes and rules out unrelated skin disorders. (Dermatopathology practice.)
Baseline labs (CBC, metabolic panel) – not diagnostic for BSS itself, but helpful to prepare for anesthesia/surgery and to rule out other causes of hair/skin changes. (Peri-operative/dermatology standard.)
D. Electrodiagnostic testing
Not routinely needed – there is no nerve or muscle disease inherent to BSS. However, electrodiagnostic studies (e.g., blink reflex EMG) may be considered in unusual cases with suspected facial nerve dysfunction influencing eyelid tone before oculoplastic surgery. This is rare and individualized. (Oculoplastic/neuromuscular practice guidance.)
E. Imaging tests
Ophthalmic imaging (anterior segment photos or OCT in older children) – documents corneal health if exposure is significant; guides treatment and follow-up. (Ophthalmology practice.)
3-D facial photography/cephalometrics – helps craniofacial teams plan reconstructive steps for macrostomia or cleft palate and track outcomes. (Craniofacial surgery planning.)
CT or MRI (selective) – reserved for surgical planning or if unusual craniofacial anatomy is suspected; not routine. (Craniofacial radiology.)
Dental panoramic X-ray (as age-appropriate) – checks jaw and teeth development if occlusion or palate issues are present. (Pediatric dentistry practice.)
Non-pharmacological treatments
1) Gentle daily emollient “seal and heal” skincare
Thick, fragrance-free ointments (e.g., petrolatum) lock in moisture, reduce friction, and protect fragile skin. Apply right after bathing and as needed. This helps the skin barrier, lowers irritation, and may reduce secondary infection risk. Mechanism: occlusive film reduces water loss and shields from friction. orpha.net
2) Lukewarm bathing with mild cleansers
Short, lukewarm baths and non-soap cleansers limit barrier damage. Pat dry (don’t rub), then apply moisturizer within minutes. Mechanism: less surfactant/heat exposure preserves lipids and proteins in thin skin. orpha.net
3) Broad-spectrum sun protection
Daily broad-spectrum sunscreen (SPF ≥30), shade, and protective clothing help prevent sunburn and photo-damage in fragile skin. Mechanism: UV filters reduce UV-induced inflammation and breakdown of dermal structures. (In the U.S., sunscreens are regulated OTC drugs; labels must meet FDA broad-spectrum and SPF testing rules.) orpha.net
4) Eye surface lubrication regimen
Schedule daytime artificial tears plus nighttime ointment to protect the cornea in ectropion. Add moisture chambers or sleep taping if dryness persists. Mechanism: increases tear film stability and reduces exposure keratopathy. NCBI+1
5) Eyelid taping / moisture shields during sleep
Gentle taping of eyelids closed (as taught by clinicians) or moisture goggles reduces overnight exposure and improves morning comfort. Mechanism: decreases evaporation and corneal desiccation. NCBI
6) Early referral to ophthalmology
Regular eye checks watch for corneal damage, infection, or vision changes. Early detection prevents ulcers and scarring. Mechanism: proactive monitoring and intervention. NCBI
7) Hair management education (trimming, depilatories)
Age-appropriate, low-risk methods (careful trimming; cautious depilatory use if tolerated) can improve comfort and appearance. Patch test first to avoid irritation. Mechanism: physical hair reduction without energy-based devices. orpha.net
8) Laser/light hair reduction in suitable candidates
When old enough and after specialist review, laser/light devices can reduce hair growth. Expect multiple sessions and maintenance; discuss rare risk of paradoxical hypertrichosis (increased hair after treatment). Mechanism: selective photothermolysis damages follicles. PMC+2PubMed+2
9) Protective clothing and cooling strategies
Light, breathable fabrics and cooling cloths help comfort in generalized hypertrichosis and fragile skin, decreasing sweat/salt irritation. Mechanism: reduces heat and friction exposure. orpha.net
10) Wound-care basics for thin, fragile skin
Use non-adherent dressings, gentle adhesive removal, and prompt cleaning if tears occur. Mechanism: prevents further barrier damage and reduces infection risk. orpha.net
11) Feeding and speech therapy when needed
If macrostomia affects feeding or early speech, therapists guide positioning, textures, and oral-motor exercises; later, they support articulation after surgical repair. Mechanism: improves function and safety while the child grows. Global Smile Foundation
12) Dental and orthodontic surveillance
Macrostomia and altered lip seal can increase drooling, oral dryness, and dental plaque; frequent dental visits and fluoride care are helpful. Mechanism: caries prevention and occlusion monitoring. Lippincott Journals
13) Psychosocial support and peer connection
Visible differences can affect self-esteem. Counseling and support groups help children and families build coping skills and resilience. Mechanism: reduces anxiety, improves quality of life. rarediseases.info.nih.gov
14) Genetic counseling for the family
Explains inheritance (often autosomal dominant), variable expression, and recurrence risk; supports informed family planning. Mechanism: risk communication and testing options. rarediseases.info.nih.gov+1
15) Scar and skin-care training for caregivers
Teaching safe adhesive removal, emollient use, and early signs of infection empowers families and reduces complications. Mechanism: skill-building for daily prevention. orpha.net
16) Eye safety education (wind/dust protection)
Wrap-around eyewear outdoors and humidified rooms indoors reduce irritation of exposed ocular surfaces in ectropion. Mechanism: physical barrier and humidity support. NCBI
17) Sleep positioning
Side or supine positioning with a small moisture chamber can reduce overnight exposure of the cornea if eyelids don’t close fully. Mechanism: reduces lagophthalmos-related dryness. NCBI
18) Staged surgical planning (team approach)
Coordinate timing of eyelid and mouth repairs with growth, airway/dental needs, and psychosocial milestones. Mechanism: maximizes safety and functional gains. Global Smile Foundation+1
19) School/teacher care plans
Written plans cover eye lubrication schedules, sun safety, and skin protection during sports; they reduce missed care at school. Mechanism: continuity of daily preventive measures. rarediseases.info.nih.gov
20) Regular, structured follow-up
Set a cadence with dermatology, ophthalmology, craniofacial surgery, dentistry, and therapy services; adjust plans as the child grows. Mechanism: ongoing risk reduction and timely interventions. rarediseases.info.nih.gov
Drug treatments
Important: There are no FDA-approved medicines specifically for Barber–Say syndrome. Drugs below are symptom-targeted (for eye surface protection, skin care, infection prevention, or hair management). Many are OTC or used off-label in pediatrics. Always individualize with specialists.
1) Ophthalmic lubricating ointments (petrolatum-based)
Thick ointments used at bedtime protect exposed eyes in ectropion. Purpose: reduce dryness and corneal injury. Mechanism: occlusive film decreases evaporation and friction; often combined with daytime artificial tears. Side effects: temporary blurred vision after application. (OTC ophthalmic demulcents are regulated under FDA monographs; AAO recommends lubrication as first-line.) AAO+1
2) Artificial tears (hypromellose, carboxymethylcellulose, etc.)
Daytime drops restore tear volume and comfort. Purpose: relieve grittiness/irritation, protect cornea. Mechanism: polymer demulcents stabilize tear film. Side effects: stinging (rare), preservative sensitivity—consider preservative-free vials if frequent use. (OTC monograph products.) NCBI
3) Erythromycin ophthalmic ointment (Rx)
Used at night both for lubrication (petrolatum base) and to prevent/treat superficial bacterial infection when exposure keratopathy is present. Class: macrolide antibiotic. Typical pediatric dosing: thin ribbon to affected eye(s) up to 4 times daily as directed. Side effects: blurred vision post-application, rare hypersensitivity. (Labeling available via FDA resources; AAO notes antibiotic ointments as preferred lubricants in exposure risk.) AAO
4) Preservative-free gel tears (carbomer/hyaluronate)
Thicker daytime gels bridge between drops and ointments. Purpose: longer relief for exposure symptoms. Mechanism: viscoelastic coating prolongs retention. Side effects: transient blur. (OTC in many markets; clinician-guided selection.) NCBI
5) Topical barrier protectants (petrolatum, dimethicone)
For atrophic skin, these OTC skin protectants form a barrier that reduces water loss and friction. Purpose: prevent tears and irritation. Mechanism: occlusion; some products include humectants. Side effects: rare folliculitis with heavy occlusion in hairy areas. (OTC skin protectant monograph products.) orpha.net
6) Topical antibiotic ointments for minor skin infections
Short courses (e.g., mupirocin) may be used if small superficial infections occur in fragile skin. Class: antibacterial. Purpose: eradicate localized impetiginization. Mechanism: inhibits bacterial protein synthesis (mupirocin). Side effects: contact irritation, resistance with overuse—use sparingly and under medical advice. orpha.net
7) Eflornithine 13.9% cream (Vaniqa®) for facial hair (selected cases)
For post-pubertal females with distressing facial hair, eflornithine slows hair growth when used twice daily; it does not remove hair and is not studied in children. Class: ornithine decarboxylase inhibitor. Purpose: reduce hair growth rate and thickness. Mechanism: blocks polyamine synthesis in follicles. Dose: thin layer to affected facial areas twice daily, at least 8 hours apart; wash hands after; use with sun protection and hair-removal methods. Side effects: mild burning/stinging, acne, rash. (FDA label shows efficacy and reversibility on stopping.) FDA Access Data+1
8) Short-course ophthalmic anti-inflammatories (selected cases)
If ocular surface inflammation complicates exposure, clinicians may prescribe short courses of steroid or cyclosporine/lifitegrast drops. Purpose: reduce inflammation and support tear film. Mechanism: immunomodulation. Side effects: steroid ocular hypertension/cataract with prolonged use—strict ophthalmology supervision required. NCBI
9) Oral analgesics (acetaminophen/ibuprofen) for post-procedure pain
Used short term after laser sessions or minor procedures. Purpose: comfort. Mechanism: central COX inhibition (acetaminophen), peripheral COX inhibition (ibuprofen). Dosing: weight-based pediatric dosing per label. Side effects: GI upset (NSAIDs). (FDA-labeled OTC analgesics.) PMC
10) Lubricating eye gels with hyaluronate
As part of a step-up regimen for severe dryness. Purpose: prolong protection between drops. Mechanism: viscoelastic hydration. Side effects: transient blur. NCBI
11) Ophthalmic antibiotic drops (if exposure-related keratitis)
When exposure causes epithelial defects with infection risk, short course antibiotic drops may be used. Class: topical antibacterials. Purpose: prevent/treat bacterial keratitis. Side effects: irritation, allergy (rare). Use guided by ophthalmology. NCBI
12) Thick zinc oxide pastes (perioral/periorbital skin protection)
Act as a physical barrier in drooling or tear overflow to prevent irritant dermatitis. Mechanism: inert shield that repels moisture. Side effects: messiness; rare contact reactions. (OTC skin protectant.) orpha.net
13) Antihistamines (selected cases of itch)
If irritation or secondary eczema causes itch, sedating or non-sedating antihistamines may be used short term. Purpose: symptomatic itch reduction, improved sleep. Side effects: sedation with first-generation agents; dosing individualized. orpha.net
14) Ophthalmic hypertonic saline (if corneal edema)
In specific scenarios, hypertonic saline can reduce epithelial edema and improve comfort—only if recommended by ophthalmology. Side effects: stinging. NCBI
15) Sodium fluoride varnish/gels (dental)
For caries prevention when lip seal is poor and drooling increases demineralization risk. Mechanism: enhances enamel resistance to acid. Side effects: avoid swallowing excess; dentist-applied varnish preferred. Lippincott Journals
16) Lubricating lip balms/ointments
Maintain lip moisture to lessen fissures and secondary infection risk before and after commissuroplasty. Mechanism: occlusive barrier. Side effects: rare contact reactions. Global Smile Foundation
17) Topical anesthetics (in-office procedures only)
Used by clinicians during minor procedures to improve comfort. Mechanism: sodium-channel blockade. Side effects: methemoglobinemia risk with certain agents in infants—used by professionals with safeguards. Global Smile Foundation
18) Post-laser topical care kits
Clinician-directed bland emollients and gentle cleansers decrease irritation after laser hair procedures. Mechanism: barrier support while skin recovers. PMC
19) Short-course oral antibiotics (if secondary skin infection)
Used only for clinical infection and tailored to local patterns. Mechanism: systemic antibacterial therapy. Side effects: GI upset, allergy—antibiotic stewardship applies. orpha.net
20) Vaccination updates and infection prevention
Not a drug for BSS itself, but staying current on routine vaccines helps reduce overall infection burden in children with fragile skin. Mechanism: active immunization. Follow national schedules. rarediseases.info.nih.gov
Dietary molecular supplements
Evidence for supplements in BSS is limited; suggestions below are general to skin barrier, wound healing, or ocular surface support. Always check for age, dose, interactions, and real deficiency.
1) Vitamin C
Supports collagen formation and wound healing; deficiency impairs skin repair. Typical dietary allowance varies by age; supplementation only if intake is poor or needs are higher. Mechanism: cofactor for prolyl/lysyl hydroxylase in collagen synthesis and antioxidant effects. rarediseases.info.nih.gov
2) Zinc
Essential for protein synthesis and immune function; deficiency delays wound healing. Supplement only to correct deficiency; excess zinc can cause copper deficiency. Mechanism: cofactor in matrix remodeling enzymes and cellular immunity. rarediseases.info.nih.gov
3) Omega-3 fatty acids (EPA/DHA)
May help reduce inflammatory skin irritation and support tear film quality in some dry eye syndromes; evidence is mixed. Mechanism: alters eicosanoid profile and meibum properties. Use age-appropriate doses. NCBI
4) Biotin (only if deficient)
Biotin deficiency can cause hair and skin changes, but routine biotin for hair growth lacks strong evidence in people without deficiency. Mechanism: coenzyme for carboxylases in fatty-acid metabolism. rarediseases.info.nih.gov
5) Vitamin A (avoid excess)
Needed for epithelial health and vision; deficiency worsens ocular surface disease. Do not exceed safe limits due to toxicity risks; consider dietary sources first. Mechanism: gene regulation for epithelial differentiation. NCBI
6) Vitamin D (correct deficiency)
Supports immune and skin health; correct measured deficiency with standard pediatric dosing. Mechanism: nuclear receptor signaling in immunity and keratinocyte differentiation. rarediseases.info.nih.gov
7) Copper (only if low from excess zinc)
Supplement only when documented deficiency occurs (e.g., from long-term high-dose zinc). Mechanism: cofactor for lysyl oxidase in collagen cross-linking. rarediseases.info.nih.gov
8) Oral rehydration/electrolyte support in hot weather
For children with heavy hair and heat intolerance, adequate fluids and electrolytes help comfort and skin health. Mechanism: supports thermoregulation and skin perfusion. rarediseases.info.nih.gov
9) Probiotics (select scenarios)
Some clinicians trial probiotics for eczema-like irritation; evidence varies and is strain-specific. Mechanism: microbiome modulation and epithelial barrier signaling. Use only with pediatric guidance. rarediseases.info.nih.gov
10) Collagen peptides (limited evidence)
Early studies suggest small improvements in skin elasticity/hydration in adults; pediatric/rare-disease data are sparse. Mechanism: bioactive peptides may signal dermal matrix metabolism. Use cautiously and prioritize nutrition from food. rarediseases.info.nih.gov
Immunity-booster / regenerative / stem-cell drugs
There are no approved stem-cell or “immunity booster” drugs for BSS. In the U.S., the FDA warns that many stem-cell products are unapproved and potentially unsafe outside specific, licensed uses (like certain blood disorders). Below are clarifications and safer, evidence-based directions your care team may discuss instead. rarediseases.info.nih.gov
1) Routine childhood vaccines (evidence-based “immune protection”)
Ensuring all standard vaccines are up to date is the safest, proven way to prevent many infections in any child, including those with fragile skin. Mechanism: antigen-specific adaptive immunity. rarediseases.info.nih.gov
2) Nutrient repletion (vitamin D, zinc, iron only if low)
Correcting measured deficiencies supports immune cell function and wound healing. Mechanism: cofactor and hormone-like immune signaling. Avoid megadoses. rarediseases.info.nih.gov
3) Lubrication-led corneal protection
Not a “drug for immunity,” but preventing corneal injury reduces infection risk—arguably the most impactful “preventive” step in ectropion. Mechanism: barrier preservation. NCBI
4) Evidence-based antibiotics for proven infections only
Use the right antibiotic, for the right bug, for the right time—this is safer than prophylaxis. Mechanism: pathogen eradication; reduces resistance risk by avoiding unnecessary use. NCBI
5) Surgical correction (eyelids/mouth) as “regenerative function”
Repairing eyelids restores protection of the eye; repairing the mouth improves seal, speech, and feeding—functionally “regenerative” even though not stem-cell therapy. Mechanism: structural restoration. Global Smile Foundation+1
6) Avoid unapproved stem-cell products
FDA cautions that many marketed stem-cell interventions are unapproved; risks include infection and immune reactions. Discuss any such proposals with a medical center and ethics review. Mechanism: risk reduction via regulatory science. rarediseases.info.nih.gov
Surgeries (procedures and why they’re done)
1) Commissuroplasty with orbicularis oris myoplasty (macrostomia repair)
Surgeons recreate a normal-sized mouth corner and re-join the lip muscle so the lips can seal. This helps feeding, drooling control, speech, and appearance. Timing depends on symptoms and growth. Global Smile Foundation+1
2) Ectropion repair (lateral tarsal strip/skin grafts/other techniques)
Procedures tighten and reposition the lower eyelid; skin grafts or flaps may be used when skin is scarce. Goal: protect cornea, reduce tearing, and improve comfort/appearance. NCBI
3) Canthoplasty / canthopexy adjuncts
These stabilize the outer eyelid corner to maintain eyelid position and reduce recurrence. Indicated when laxity is significant. NCBI
4) Revision procedures after growth
Children grow, and tissues change. Secondary touch-ups may be needed to maintain eyelid protection or refine lip symmetry and oral competence. Global Smile Foundation
5) Limited hair-bearing skin procedures (selected cases)
When dense hair causes recurrent irritation in small areas, surgeons may consider targeted follicular destruction or excision with careful closure; usually, energy-based hair reduction is preferred before surgery. PMC
Preventions
Daily emollients and gentle bathing to protect fragile skin. orpha.net
Sun protection (broad-spectrum sunscreen, hats, shade). orpha.net
Scheduled eye lubrication and protective sleep measures. NCBI
Early ophthalmology checks to prevent corneal injury. NCBI
Cool clothing and hydration during hot weather. rarediseases.info.nih.gov
Safe hair care routines; delay lasers until appropriate and specialist-guided. PMC
Prompt care for skin tears with non-adherent dressings. orpha.net
Dental prevention (fluoride, regular cleanings) to protect teeth. Lippincott Journals
School/child-care care plans for eye drops, sun, and skin care. rarediseases.info.nih.gov
Genetic counseling for family planning and risk understanding. rarediseases.info.nih.gov+1
When to see doctors (red flags)
See a clinician urgently for eye pain, light sensitivity, worsening redness, or blurred vision—these may signal corneal injury or infection in ectropion. Also seek prompt care for fever with spreading skin redness (possible skin infection), deep skin tears that won’t stop bleeding, feeding difficulty or choking, poor weight gain, or new breathing or speech concerns. Schedule regular visits with dermatology, ophthalmology, craniofacial surgery, dentistry, and therapy teams to track growth and function. NCBI+2orpha.net+2
What to eat and what to avoid
Eat/Include:
Balanced diet with enough protein for skin repair (eggs, fish, legumes). rarediseases.info.nih.gov
Fruits/vegetables rich in vitamin C (citrus, berries, peppers) for collagen support. rarediseases.info.nih.gov
Whole grains and healthy fats to support energy and skin barrier (olive oil, nuts—age appropriate). rarediseases.info.nih.gov
Adequate fluids; extra in heat to reduce irritant salt on skin. rarediseases.info.nih.gov
Dairy or fortified alternatives for vitamin D and calcium; supplement only if levels are low. rarediseases.info.nih.gov
Avoid/Limit:
- Harsh spices/very acidic foods if perioral skin is irritated (individualize). orpha.net
- Sugary drinks that worsen dental caries risk, especially with drooling/lip-seal issues. Lippincott Journals
- Excess vitamin A or D supplements without testing (toxicity risk). rarediseases.info.nih.gov
- Unregulated “hair growth” or “stem-cell” supplements/therapies marketed without approvals. rarediseases.info.nih.gov
- Extreme diets that risk nutrient deficiencies critical for healing. rarediseases.info.nih.gov
FAQs
1) Is there a cure for Barber–Say syndrome?
No single cure exists. Care targets each feature—hair, skin, eyes, and mouth—to protect health and improve function and appearance over time. orpha.net
2) What gene is involved?
Some cases are caused by changes in TWIST2. Inheritance can be autosomal dominant, though many cases are new mutations. Genetic testing and counseling can help families understand risks. ScienceDirect+1
3) Will the extra hair go away on its own?
Hair often persists. Trimming and gentle methods are first steps; laser/light reduction can help selected patients but needs multiple sessions and carries rare risks like paradoxical hypertrichosis. PMC+1
4) Is laser hair removal safe for children?
Data in young children are limited; decisions are case-by-case with dermatology. Timing, skin type, device choice, and eye protection are critical. PMC
5) How dangerous is ectropion?
Untreated, it can injure the cornea. Lubrication is first-line; surgery is common if lubrication isn’t enough. Regular eye checks are essential. NCBI
6) Can macrostomia be repaired?
Yes. Commissuroplasty and muscle repair can improve appearance, lip seal, feeding, and speech. Timing is individualized. Global Smile Foundation+1
7) Is the skin infection risk higher?
Thin, fragile skin tears more easily, which can raise infection risk. Gentle care, barrier ointments, and prompt wound care help. orpha.net
8) Are there medicines specifically for BSS?
No. Medicines are used to treat symptoms (e.g., eye lubrication, antibiotics if infection). Eflornithine cream may slow facial hair in post-pubertal females but is not for young children. FDA Access Data
9) What specialists should we see?
Dermatology, ophthalmology, plastic/craniofacial surgery, dentistry/orthodontics, speech/feeding therapy, and genetics. Team care works best. rarediseases.info.nih.gov
10) Will my child need multiple surgeries?
Possibly. As children grow, eyelid position and mouth symmetry can change; occasional revisions are common. Global Smile Foundation
11) Can vitamins or supplements fix BSS?
Supplements don’t “cure” BSS. Correcting true deficiencies (e.g., vitamin D, zinc) supports general health, but megadoses can be harmful. rarediseases.info.nih.gov
12) Are stem-cell therapies available?
No approved stem-cell therapies exist for BSS. Be cautious with unapproved clinics; discuss research trials only at recognized centers. rarediseases.info.nih.gov
13) How do we manage school and sports?
Provide a care plan for eye drops, sun protection, emollient reapplication, and safe participation. Choose low-friction clothing and protective eyewear. rarediseases.info.nih.gov
14) Could another family member have it?
If a parent has a TWIST2 change, each child has a 50% chance of inheriting it. Genetic counseling explains testing and risks. ScienceDirect
15) Where can we read more?
Trusted summaries include Orphanet and GARD; clinicians can locate the 2015 TWIST2 paper and case reports to guide care. orpha.net+2rarediseases.info.nih.gov+2
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.
