Palmoplantar Keratoderma and Congenital Alopecia, Stevanović Type

Palmoplantar keratoderma and congenital alopecia, Stevanović type is a very rare genetic skin condition. Babies are usually born with little or no scalp or body hair (congenital alopecia). As they grow, the skin on their palms and soles becomes very thick and hard (palmoplantar keratoderma). Some people also have white nails (leukonychia) or other nail changes. This form is autosomal dominant, which means a single altered copy of the gene can cause the condition. The main known gene is GJA1, which makes the connexin-43 gap-junction protein. Changes in GJA1 disrupt cell-to-cell signaling in skin and hair follicles and can lead to thickened skin and hair loss. This Stevanović type is also called PPKCA1 in some databases. PMC+3ScienceDirect+3informatics.jax.org+3

PPK-CA, Stevanović type is a rare, autosomal-dominant genodermatosis characterized by thickened skin on the palms and soles (palmoplantar keratoderma) together with congenital absence or near-absence of scalp and body hair (alopecia/hypotrichosis). Compared with more severe PPK–alopecia syndromes, the Stevanović form is typically benign and not associated with severe hand complications (e.g., progressive constricting bands are unusual). rarediseases.info.nih.gov+1

How it differs from the recessive type (PPK-CA type 2): there is another, autosomal recessive form—sometimes called PPKCA2—that tends to cause progressive hand and toe problems such as finger tightening (sclerodactyly), constricting bands (pseudoainhum), and even cataracts. Recent studies link that recessive type to LSS (lanosterol synthase) mutations. The Stevanović (dominant) type usually does not have those severe hand complications. NCBI+2Orpha+2

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Other names

These are the labels you may see in medical databases or papers for the Stevanović (dominant) type:

• Palmoplantar keratoderma and congenital alopecia, Stevanović type (PPK-CA, Stevanović type)

• Palmoplantar keratoderma and congenital alopecia-1 (PPKCA1)

• Autosomal dominant palmoplantar keratoderma and congenital alopecia

• Autosomal dominant palmoplantar hyperkeratosis and congenital alopecia

• Keratoderma-hypotrichosis-leukonychia totalis syndrome (KHLS)
  All of the above refer to the same dominant spectrum anchored in GJA1/connexin-43. ScienceDirect+2NCBI+2

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Types

1) Dominant (Stevanović) type = PPKCA1.
This is the focus here. Main signs: thick skin on palms/soles, hair loss from birth, sometimes white nails. Gene: GJA1. Inheritance: autosomal dominant. ScienceDirect+1

2) Recessive type = PPKCA2.
Less common in literature, but recognized: hair loss from birth, progressively severe palmoplantar thickening that can lead to finger tightening, bands around digits, and cataracts. Gene recently implicated: LSS (lanosterol synthase). Inheritance: autosomal recessive. NCBI+1

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Causes

In rare disorders, “causes” mostly mean genetic mechanisms and factors that modify severity. Below are 20 plainly worded, evidence-based causes or contributors.

1. GJA1 (connexin-43) mutation (classic cause).
   A well-documented single-letter change in the gene—GJA1 p.Gly8Val (G8V)—can produce the full picture of thick palms/soles, lifelong hair loss, and white nails. This mutation alters gap-junction signaling between skin cells. PubMed+1

2. Dominant inheritance.
   Only one altered GJA1 copy is enough, so it can pass directly from an affected parent to a child, with a 50% chance in each pregnancy. ScienceDirect

3. Connexin-43 dysfunction in the epidermis.
   Connexin-43 forms channels that let skin cells share small signals. Disrupted channels can push keratinocytes to over-thicken, causing keratoderma. PMC+1

4. Connexin-43 dysfunction in hair follicles.
   Hair follicles need tight cell-to-cell communication for normal growth. When Cx43 is abnormal, follicles may not form or cycle correctly, causing alopecia from birth. The Company of Biologists+1

5. “Gain-of-function” channel behavior.
   Some Cx43 mutations increase “hemichannel” activity, upsetting calcium and other signals that guide skin and hair growth. MDPI

6. Other GJA1 variants reported in connexin-skin disease.
   While G8V is the hallmark for Stevanović type, the gene is pleiotropic; other missense changes in GJA1 cause related keratinization disorders, showing how sensitive skin is to Cx43 changes. ScienceDirect

7. Dose and mosaic effects.
   Because the disorder is dominant, even a mosaic (patchy) presence of the variant in skin may influence severity and distribution. (Inference supported by connexin-skin literature on dominant, often mosaic presentations.) ScienceDirect

8. Keratinocyte differentiation shift.
   Abnormal Cx43 can interfere with signals that tell keratinocytes when to stop dividing and start maturing, leading to thick stratum corneum. ScienceDirect+1

9. Mechanical stress (modifier).
   Pressure and friction on palms/soles make keratoderma worse in many PPKs, including PPK-CA, by triggering more callus formation. (General PPK mechanism.) UpToDate

10. Dryness and barrier damage (modifier).
    A weakened skin barrier thickens more to protect itself. This can worsen fissures and thickening in PPK. (General PPK care principle.) Medical Journals

11. Climate (modifier).
    Heat and humidity can increase maceration and softening, then cracking after drying; cold/dry air can also trigger more thickening. (General PPK clinical guidance.) Medical Journals

12. Secondary infection (modifier).
    Fissures can get infected, increasing inflammation and keratin production. (General PPK consideration.) Medical Journals

13. Nail-matrix involvement.
    The same gene defect can affect nail-matrix keratinocytes, causing leukonychia in some patients. OUP Academic

14. Hair-cycle signaling defects.
    Disrupted gap-junction signals can block normal hair cycling (anagen–catagen–telogen), keeping hair sparse or absent from birth. OUP Academic

15. Embryonic morphogenesis pathways.
    Connexin-based communication guides tissue patterning during development; defects here can leave permanent hair and skin abnormalities at birth. ScienceDirect

16. Stem-cell niche disturbance.
    Cx43 is important in stem-cell niches; altered signaling may impair follicle stem-cell function and epidermal repair. PMC

17. Non-GJA1 genes (recessive type, for differential).
    When the presentation includes severe hand complications/cataract, LSS variants (recessive) are now implicated—useful for genetic counseling and for telling types apart. jidonline.org

18. Gene–environment interaction.
    Even with the same mutation, day-to-day load (standing jobs, tight shoes) can affect keratoderma thickness and fissure risk. (General PPK principle.) Medical Journals

19. Variant-specific channel behavior.
    G8V and other Cx43 variants can form channels that look normal but behave abnormally, subtly changing ion/second-messenger flow. PubMed

20. Family segregation.
    Multiple families show the mutation tracks with disease over generations, confirming causality and dominant transmission. PubMed

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Symptoms and signs

1. Hair absent or very sparse from birth.
   Most people have little or no scalp hair, eyebrows, or eyelashes (congenital alopecia or hypotrichosis). ScienceDirect

2. Thick skin on palms and soles.
   The skin builds up as firm, yellowish, or waxy callus that can feel hard. ScienceDirect

3. Painful cracks (fissures).
   Deep splits can form in the thick skin, especially at pressure points, and can bleed or hurt when walking. (General PPK feature.) Medical Journals

4. White nails (leukonychia).
   Some have chalk-white nails on fingers and toes; nails may still be structurally okay or mildly dystrophic. OUP Academic

5. Nail brittleness or slow growth (sometimes).
   Nails can chip or feel thickened; not everyone has this. ScienceDirect

6. Foot pain with walking or standing.
   The thicker the plantar skin, the more pressure on nerves and joints. (PPK principle.) Medical Journals

7. Hand discomfort with gripping.
   Hard callus can crack when flexing, making manual tasks sore. (PPK principle.) Medical Journals

8. Recurrent skin infections in fissures.
   Cracks can let in bacteria or fungi; redness, swelling, or discharge may follow. (PPK principle.) Medical Journals

9. Burning or itching over callused areas.
   Thickened skin can itch or burn after activity. (PPK principle.) Medical Journals

10. Cosmetic distress or social impact.
    Visible hair loss and nail whiteness can affect self-image and mood; this is common in inherited alopecia disorders. (General alopecia impact.) Wiley Online Library

11. Hyperhidrosis or maceration in thick skin (sometimes).
    Moisture may trap under the keratoderma, softening then re-hardening with cracks. (PPK principle.) Medical Journals

12. Callus accentuated by friction.
    Tight shoes or repetitive manual labor tends to worsen thickening. (PPK principle.) UpToDate

13. Hair that never grows to normal length.
    If present, hair is often short, sparse, or fragile throughout life. ScienceDirect

14. Normal sweating, teeth, and hearing in the dominant type.
    In KHLS/PPK-CA1, other organs are usually fine; this helps separate it from other ectodermal dysplasias. OUP Academic

15. No severe hand contractures/cataracts in the dominant type.
    Those complications point more to the recessive (PPK-CA2) form. Orpha

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Diagnostic tests

A) Physical examination

1. Dermatology full-skin exam.
   Doctor documents thickness pattern on palms/soles, any fissures, elbows/knees involvement, and infection signs. This establishes baseline severity for PPK. UpToDate

2. Hair and scalp exam.
   Confirms congenital alopecia or sparse hair; checks eyebrows/eyelashes and body hair. ScienceDirect

3. Nail inspection.
   Looks for leukonychia and any dystrophy to support the KHLS/PPK-CA1 spectrum. OUP Academic

4. Hand/foot function check.
   Assesses pain, gait, grip, and range of motion; important for quality-of-life planning. (General PPK care.) Medical Journals

5. Family exam and pedigree.
   Because it’s usually autosomal dominant, examining relatives helps show vertical transmission. ScienceDirect

B) “Manual” bedside tests

6. Dermoscopy (handheld scope).
   Noninvasive magnification shows skin ridge accentuation, fissure edges, and nail plate whiteness without drilling or biopsy. Medical Journals

7. Hair-pull test and trichoscopy.
   Gentle tug assesses fragility; trichoscopy visualizes miniaturized or absent follicles common in congenital alopecia. (General alopecia assessment.) UpToDate

8. Pressure/pain mapping.
   Palpation pinpoints tender callus and areas at risk for fissure/infection to guide paring and padding. (PPK clinic practice.) Medical Journals

9. Scale thickness assessment.
   Manual paring (clinical debridement) estimates depth and guides emollient/keratolytic strength. (PPK care.) Medical Journals

10. Photographic severity scoring.
    Standardized photos help track changes with treatment and load reduction over time. (PPK monitoring.) Medical Journals

C) Laboratory & pathological tests

11. Targeted GJA1 genetic testing (dominant type).
    Confirms Stevanović/PPKCA1; classic variant reported is GJA1 p.Gly8Val (G8V). Panel or single-gene testing can be used. PubMed

12. If phenotype suggests recessive form, test LSS.
    Biallelic LSS variants have been identified in PPK-CA type 2 with progressive hand/toe complications and cataracts. jidonline.org

13. Skin biopsy (histopathology).
    Shows hyperkeratosis and acanthosis typical of PPK; biopsy also helps rule out other keratodermas or psoriasis. (General PPK histology.) UpToDate

14. Mycology (KOH/culture) when scaling is atypical.
    Rules out tinea pedis/manuum superinfection that can mimic or worsen keratoderma. (PPK differential.) Medical Journals

15. Basic labs for alternative alopecia causes (when unclear).
    Ferritin/iron studies, thyroid profile, zinc, vitamin D if the history is not clearly congenital—useful to exclude common acquired causes. (General alopecia workup.) UpToDate

16. Whole-exome sequencing (when single-gene tests are negative).
    Catches atypical/novel variants and clarifies inheritance for family counseling. PubMed

17. ClinVar / variant interpretation.
    Pathogenic/likely pathogenic calls for GJA1 variants (e.g., c.23G>T) support the diagnosis and help counsel family members. NCBI

D) Electrodiagnostic tests

18. QSART (quantitative sudomotor axon reflex test).
    If a patient reports altered sweating in thick skin, QSART can document sweat output; most PPK-CA1 patients have normal systemic function, so this is situational. (Autonomic testing principle in skin disease.) UpToDate

19. Sympathetic skin response (SSR).
    Occasionally used in research/complex cases to measure skin electrical responses; not routinely required for diagnosis but can document autonomic integrity in palms/soles. (Electrodiagnostic overview for skin/autonomic function.) UpToDate

E) Imaging and advanced noninvasive skin tools

20. Reflectance confocal microscopy or high-frequency ultrasound.
    These imaging tools visualize epidermal thickening and fissure depth without biopsy; dermoscopy is the practical first step, but RCM/ultrasound can add detail in clinics that have them. (Noninvasive imaging in keratinizing disorders.) Medical Journals

Non-pharmacological treatments

1. Daily emollients with humectants (urea, lactic acid, glycerin). Restore barrier water and soften scale; urea additionally modulates keratinocyte differentiation and acts as a keratolytic at higher strengths. Apply twice daily; increase during dry seasons. PMC+1

2. Keratolytic cycles (urea 20–40%, lactic acid 12%). Reduce thickness to limit fissuring; often used nightly under occlusion, then maintain with lower-strength moisturizers. Wiley Online Library+1

3. Soak-and-pare routine. Warm water soaks (10–15 min), gentle mechanical paring with a podiatry file, then keratolytic + emollient; repeat 2–3×/week. PMC

4. Callus offloading/orthotics. Reduce plantar pressure with insoles/top-covers; markedly decreases painful fissures at weight-bearing points. PMC

5. Occlusion therapy. Plastic wrap or hydrocolloid plasters overnight after urea/lactic acid accelerates softening; discontinue if maceration/infection. PMC

6. Antiperspirant protocols (aluminum salts) for hyperhidrosis. Less moisture = less maceration and splitting. Medscape

7. Blister/fissure protection. Liquid bandage or hydrocolloids across linear cracks to improve pain and healing. PMC

8. Footwear and glove optimization. Wide toe box, cushioned soles, moisture-wicking socks; protective gloves for wet work. PMC

9. Infection prevention. Prompt cleansing, barrier ointments for splits, and culture-guided care if drainage appears. PMC

10. Gentle keratolytic peels in clinic. Periodic clinician-directed debridement avoids over-thinning and injury. PMC

11. Behavioral friction reduction. Silicone grips, padded handles, task rotation at work. PMC

12. Climate and humidity management. Humidifiers and emollient up-titration in dry seasons to reduce fissuring. PMC

13. Sun-smart scalp care. Because of alopecia, strict scalp photoprotection (UPF hats, sunscreen) to prevent burns. PMC

14. Psychosocial support & cosmetic options. Wigs, micro-pigmentation, counseling when appearance affects quality of life. PMC

15. Education on maintenance vs “cure.” Emphasize chronic nature; consistent routines outperform sporadic “heavy” treatments. PMC

16. Dermoscopy-guided self-monitoring. Photos to track thickening/fissures and response to care. PMC

17. Dietary pattern for skin barrier (adjunct). Balanced diet with adequate essential fatty acids and fiber supports barrier lipids and systemic inflammation control (adjunctive only). PMC+1

18. Occupational health adjustments. Limit prolonged wet work and repetitive shear tasks where feasible. PMC

19. Podiatry partnership. Regular professional debridement + orthotic review reduces painful flares. PMC

20. Genetic counseling. Discuss autosomal-dominant inheritance, variability, and family planning. NCBI

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Drug treatments

Reality check: No drug is approved for Stevanović-type PPK-CA. The options below are off-label, adapted from hereditary/acquired PPK care, and supported by general dermatology evidence. For FDA source material, I cite official labels (accessdata.fda.gov) describing each drug’s class, dosing, warnings, and mechanisms in their approved indications; clinicians extrapolate cautiously to PPK based on keratinization biology.

Systemic retinoids (strongest class evidence in hereditary PPK broadly):

1. Acitretin (oral retinoid). Class: retinoid. Typical dosing: 10–25 mg daily, titrated; strict pregnancy contraindication with long post-therapy avoidance. Purpose/mechanism: normalizes epidermal differentiation, reducing hyperkeratosis thickness; most consistent systemic benefit across hereditary PPKs, though responses vary and relapse occurs after stopping. Key safety: teratogenicity, mucocutaneous dryness, lipids/LFT abnormalities. Label source (class details/safety): SORIATANE® label. FDA Access Data

2. Isotretinoin (oral retinoid). Class: retinoid. Dosing (acne label): weight-based courses; in PPK, low-to-moderate daily dosing is sometimes used off-label. Purpose/mechanism: keratinization modulation; may benefit hyperkeratosis in select cases. Key safety: iPLEDGE teratogenicity program; mucocutaneous and lab abnormalities. Label source: ACCUTANE®/isotretinoin labeling. FDA Access Data+1

3. Tazarotene (topical retinoid 0.05–0.1%). Class: topical RAR-selective retinoid. Use: nightly to plaques (thin layer), often combined with keratolytics. Purpose/mechanism: gene-expression modulation of keratinocyte differentiation. Key safety: irritation, photosensitivity; avoid in pregnancy. Label source: TAZORAC®/AVAGE® labeling. FDA Access Data+1

Key keratolytics/emollients (labeled for xerosis/keratin disorders; used here for plaque control):

4. Ammonium lactate 12% cream/lotion. Class: alpha-hydroxy acid emollient. Dosing: 1–2× daily to thickened skin. Purpose/mechanism: humectant + gentle keratolysis; softens scale and reduces fissuring. Safety: stinging on broken skin; sun sensitivity. Label source: Lac-Hydrin® labeling. FDA Access Data+1

5. Salicylic acid (topical keratolytic). Class: keratolytic (OTC and Rx strengths). Use: thin film to plaques; avoid large areas in children. Mechanism: corneocyte desmosome disruption → scale release. Safety: irritation/rare salicylate toxicity with overuse. FDA references (keratolytic category notes): examples within FDA records. FDA Access Data+1

(Additional clinic-used, off-label agents sometimes combined for comfort/itch—like topical corticosteroids for fissure rim inflammation or antiseptics for macerated areas—are individualized; labels are not disease-specific and are omitted here for brevity.) PMC

Evidence context: Reviews of hereditary PPK management consistently identify oral retinoids as the most effective systemic option (not universal, tolerance varies), with topical keratolytics/emollients forming the backbone of day-to-day care. PubMed+1

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Dietary molecular supplements

There are no supplements proven to modify the genetic course of Stevanović-type PPK-CA. Some nutrition strategies may support the skin barrier (adjuncts, not treatments):

1. Urea-supporting topical regimen (not oral supplement): high-strength topical urea directly improves hydration/keratolysis. Evidence is topical, not dietary. PMC

2. Omega-3 fatty acids (EPA/DHA). Small human/experimental data suggest barrier-lipid and anti-inflammatory effects; consider as part of a balanced diet. ScienceDirect

3. Dietary fiber → short-chain fatty acids (SCFAs). Mechanistic data show improved epidermal barrier integrity via SCFAs; extrapolative for PPK. Nature

4. General micronutrient adequacy (vitamin D, zinc, iron) for overall skin/hair health—addresses background deficits but does not treat PPK-CA. PMC
   (Remaining “supplements” lack disease-specific evidence; routine use should be conservative and clinician-guided.) PMC

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Immunity-booster/regenerative/stem-cell drugs

There are no FDA-approved “immune-booster/regenerative/stem-cell” drugs for PPK-CA. Systemic retinoids (above) remain the main pharmacologic tool for keratinization disorders; any regenerative approaches are investigational and not established for this condition. PubMed

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Surgeries

Surgery is rarely needed in Stevanović type. When severe constricting bands (pseudo-ainhum) threaten digits—a scenario more typical of recessive forms—options include: (1) circumferential band excision with Z-plasty, (2) staged Z-plasties, (3) skin grafting when deficits are large, (4) release with local flaps, and (5) repeat procedures for recurrence. Case literature across PPK entities shows variable recurrence; medical retinoids may help reduce re-thickening post-release. PMC+3PubMed+3ScienceDirect+3

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Preventions

Daily emollients, regular keratolytics, reduce friction/pressure, treat hyperhidrosis, protect fissures, humidify dry air, optimize footwear/gloves, prompt infection care, sun-protect the scalp, and keep a maintenance calendar to prevent “boom-and-bust” cycles. These measures reduce symptoms even though they cannot prevent the genetic condition. PMC

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When to see a doctor

Seek dermatology review for new/worsening pain, bleeding fissures, signs of infection, rapid plaque thickening, functional hand/foot limitations, or significant psychosocial distress; also before starting retinoids (systemic or topical) because of contraindications and monitoring. Genetic counseling is recommended for affected families. FDA Access Data+1

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What to eat / what to avoid

Eat: (1) balanced diet with omega-3-rich fish; (2) high-fiber foods that nurture SCFA production; (3) adequate protein for skin repair; (4) water for hydration; (5) micronutrient-dense fruits/vegetables. Avoid/limit: (6) very low-fat fad diets (can reduce essential fatty acids); (7) excess alcohol (worsens dryness); (8) high-sugar ultra-processed patterns that may worsen systemic inflammation; (9) dehydration; (10) self-supplement megadoses without clinician input. These measures support barrier function but do not treat the genetic disease. PMC+1

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FAQs

1) Is there a cure? No definitive cure; management aims to control thickness, pain, and fissures with daily care and occasional retinoids. PubMed
2) Will hair grow back? Congenital alopecia in Stevanović type is generally lifelong; cosmetic solutions (wigs, scalp protection) help quality of life. rarediseases.info.nih.gov
3) Are retinoids safe? They can be effective but require strict pregnancy precautions and lab monitoring; dermatologist supervision is essential. FDA Access Data+1
4) Are there targeted gene therapies? None yet for this condition; research on connexin-43 biology is ongoing. MDPI
5) Will surgery be needed? Rare in Stevanović type; considered mainly for constriction bands, which are uncommon here. PubMed
6) What’s the inheritance risk? Autosomal-dominant: each child has a ~50% chance if a parent is affected; expressivity varies. NCBI
7) How is it confirmed? Clinical pattern + GJA1 genetic testing confirm; biopsy rules out mimics. PubMed
8) Are topical retinoids helpful? They may thin plaques but often irritate; start low and combine with emollients. FDA Access Data
9) Do moisturizers really matter? Yes—urea/lactic acid regimens are the backbone of comfort and crack prevention. PMC
10) Is pseudo-ainhum expected? Not typically in Stevanović type; monitor anyway for tight keratotic rings. PubMed
11) Can hyperhidrosis be treated? Yes—antiperspirants and routine drying reduce maceration and pain. Medscape
12) Are antibiotics needed? Only for documented infection of fissures; culture when drainage or malodor appears. PMC
13) Can diet reverse plaques? No; diet can support the barrier but does not modify the genetic defect. PMC
14) Are there clinical trials? Trials are rare given disease rarity; broader PPK studies may exist—ask your dermatologist/genetics team. JAMA Network
15) What’s the long-term outlook? Typically stable, life-long, with symptoms fluctuating by care routine, climate, and mechanical stress. PMC

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 04, 2025.

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