Al-Gazali syndrome is a very rare, inherited condition. Babies are small before birth and after birth. Many joints are stuck in bent positions (joint contractures), the fingers may be bent (camptodactyly), and the feet may turn inward (clubfoot). The eyes often have “anterior segment” problems (the clear front part of the eye and the iris). Most affected babies become very sick early, and the condition can be life-limiting. Doctors believe it follows an autosomal recessive pattern, which means a child gets a non-working copy of the same gene from both parents. malacards.org+1
Al-Gazali syndrome (ALGAZ) is a very rare, inherited condition. Babies have growth problems before birth, tight joints (contractures), bone differences, eye front-segment problems, and often pass away early in life. It is usually autosomal recessive, which means both parents silently carry a non-working gene copy. The exact genetic cause is still being clarified; a few reports point to overlap or “look-alike” changes in connective-tissue genes (for example B3GALT6) and a distinct, similarly named Al-Gazali skeletal dysplasia that is now linked to ADAMTSL2 (this is a different diagnosis). There is no disease-modifying drug yet. Care focuses on comfort, safe breathing and feeding, contracture prevention, eye protection, and family counseling. Oxford Academic+4Genetic Rare Disease Center+4NCBI+4
Al-Gazali syndrome is an ultra-rare genetic disorder first described in families where babies were born very small, with tight joints (especially fingers and feet), clubfoot (talipes equinovarus), a small mouth, and eye anomalies at the front of the eye (for example, sclerocornea or cloudy cornea). Many babies also have bent fingers (camptodactyly), bone differences, and feeding and breathing difficulties soon after birth. Sadly, early death is common because of severe body system involvement. Doctors recognized that the pattern tends to run in families in an autosomal recessive way: parents are healthy carriers; when both pass on the non-working copy, the baby is affected. Because it is so rare, the exact gene is not fixed yet; some babies with very similar features have changes in B3GALT6, a gene needed to build the “sugar chains” (glycosaminoglycans) that support cartilage, eye, skin, and bone. In parallel, a different entity historically called “Al-Gazali skeletal dysplasia” has now been tied to ADAMTSL2 and represents the lethal end of that gene’s disorder spectrum; that condition is not the same as Al-Gazali syndrome described here, but the name overlap can be confusing. Oxford Academic+5Genetic Rare Disease Center+5NCBI+5
Other names
Doctors and databases list several alternate names. You may see: “Al-Gazali–Al-Talabani syndrome” or “Eye defects, arachnodactyly, cardiopathy” (a descriptive label noted in medical databases). These refer to the same clinical picture reported by Prof. Lihadh Al-Gazali and colleagues in the 1990s. NCBI+1
In 1994, Al-Gazali and co-authors described siblings with growth delay before birth, eye defects in the front of the eye, long thin fingers (arachnodactyly), heart problems, and very early death. Later families with a very similar pattern were reported. This cluster of features became known as Al-Gazali syndrome. United Arab Emirates University+1
Types
There is no official, universally accepted “type 1/type 2” system for Al-Gazali syndrome. Because only a few families are known, doctors usually group cases by which organs are most affected and by severity:
“Classic” neonatal form – severe growth restriction before birth, multiple joint contractures, clubfeet, facial features (small mouth), eye anterior-segment anomalies, often heart defects, and early lethality. malacards.org
Ocular-predominant form – the same general pattern but with especially obvious front-of-eye problems (cloudy cornea, small cornea, iris under-development) and vision concerns from birth. (These specific eye findings are examples of “anterior segment anomalies,” which vary case-to-case.)
Skeletal-predominant form within a broader “linkeropathy” spectrum – some patients described as “Al-Gazali-like” have changes in a gene called B3GALT6, which is part of the pathway that builds glycosaminoglycans (GAGs) for cartilage and connective tissue. Many experts view Al-Gazali syndrome as overlapping the B3GALT6-related spectrum of disorders. PubMed+1
Practical take-away: these “types” are clinical groupings to explain patterns. They are not official subtypes in a formal classification.
Causes
Core cause:
Pathogenic variants (mutations) in B3GALT6: At least one patient originally labeled “Al-Gazali syndrome” had harmful changes in this gene. B3GALT6 makes an enzyme (β3GalT6) that helps build the “linker” that starts GAG chains (such as chondroitin sulfate and dermatan sulfate) on proteoglycans. When this step fails, connective tissue in bone, cartilage, eye, and heart cannot form normally. PubMed+1
How that single genetic problem leads to many body problems (mechanisms and contributors):
- Autosomal recessive inheritance – a child must inherit two non-working copies (one from each parent). Parental health is usually normal. malacards.org
- Reduced GAG chain formation – fewer/abnormal GAGs weaken cartilage templates used to build bones and joints. PubMed
- Abnormal collagen fibrils – proteoglycan defects disturb collagen scaffolding, stiffening or weakening tissues. Monarch Initiative
- Skeletal modeling errors – long bones and spine develop with deformity, causing contractures and clubfoot. malacards.org
- Tendon and joint capsule stiffness – tight peri-articular tissues limit motion before birth, resulting in fixed bends at birth. malacards.org
- Anterior segment eye development disturbance – cornea/iris structures that need normal extracellular matrix don’t form correctly.
- Small mouth and craniofacial differences – altered connective tissue and bone growth change facial shape and oral size. malacards.org
- Heart connective tissue involvement – valves and outflow tracts rely on proteoglycans; some babies develop congenital heart disease. United Arab Emirates University
- Growth restriction before birth – abnormal placenta-fetal connective tissue and overall skeletal dysplasia limit growth. malacards.org
- Early breathing problems – chest wall stiffness and facial/oral features can complicate breathing and feeding. malacards.org
- Fragile skin/soft tissue tendencies in some linkeropathies may add wound-healing challenges. Monarch Initiative
- Variable expressivity – the same gene can cause different severity even within a family. malacards.org
- Consanguinity increases risk of two carriers having an affected child (seen in original reports). United Arab Emirates University
- Founder effects in small populations can cluster cases. (General genetics principle relevant to rare AR disorders.) malacards.org
- ER quality-control stress – some B3GALT6 changes misfold the enzyme and trigger cellular stress responses. UAE Ministry of Health
- Proteoglycan-rich tissues most affected – cartilage, cornea, heart valves, and skin show the greatest impact. Monarch Initiative
- Secondary muscle imbalance from fixed joints worsens deformities over time. malacards.org
19) Feeding and nutrition issues from small mouth or clefting can slow growth further. United Arab Emirates University - Perinatal complications (respiratory, cardiac) contribute to early lethality in severe cases.
Symptoms and signs
Poor growth before birth (IUGR): Babies measure small on prenatal scans and at delivery. malacards.org
Joint contractures: Several joints are stuck in a bent position at birth and are hard to move.
Camptodactyly: Fingers remain flexed and do not straighten fully. malacards.org
Clubfoot (talipes equinovarus): The feet point inward and downward. malacards.org
Small mouth (microstomia): The mouth opening is smaller than usual, which can make feeding hard. malacards.org
Anterior segment eye anomalies: The clear front of the eye, the cornea, or the iris may not form normally; vision may be reduced.
Facial differences: Features may include a narrow mouth and long slender fingers (arachnodactyly). United Arab Emirates University
Possible heart defects: Some babies have congenital heart problems. United Arab Emirates University
Clefting in some cases: Cleft lip and/or palate were reported in early descriptions. United Arab Emirates University
Stiff chest wall and weak breathing: The rib cage can be rigid from joint/tissue changes, making breathing tough. malacards.org
Feeding problems: Small mouth or clefting can make sucking and swallowing difficult. United Arab Emirates University
Short limbs or limb shape changes: Bone growth is abnormal, leading to limb appearance differences. malacards.org
Spinal changes: The spine may show abnormal curvatures or vertebral shape. malacards.org
Low muscle bulk from disuse: Fixed joints reduce movement and muscle development. malacards.org
Early severe illness: Because many systems are involved, the condition can be life-limiting in the newborn period.
Diagnostic tests
A) Physical examination
Growth check (weight/length/head size): Confirms small size and tracks growth over time. malacards.org
Full joint exam: Notes which joints are stuck and how much they can move.
Hand/feet inspection: Looks for camptodactyly and clubfoot to guide early splinting or casting. malacards.org
Eye exam by pediatrician: Screens for cloudy cornea or other front-of-eye changes that need urgent eye care.
Heart and lungs check: Listens for murmurs or breathing difficulty that require immediate testing. United Arab Emirates University
B) Manual/bedside clinical tests
Range-of-motion testing: Gentle movement measures how stiff each joint is and sets therapy goals. malacards.org
Neuromuscular tone assessment: Distinguishes joint stiffness from nerve or muscle problems. malacards.org
Orthopedic contracture scoring (e.g., clubfoot scoring): Standard bedside scores help plan casting or surgery timing. malacards.org
Ophthalmic slit-lamp exam: A lighted microscope lets an eye doctor view the cornea and iris in detail.
Feeding and airway evaluation: Bedside swallow and airway checks identify risks for aspiration and breathing trouble. United Arab Emirates University
C) Laboratory and pathological tests
Genetic testing (targeted B3GALT6 or exome): Looks for two harmful changes that confirm a diagnosis and inform family counseling. NCBI+1
Parental carrier testing: Checks if each parent carries one non-working copy, supporting autosomal recessive inheritance. malacards.org
Glycosaminoglycan (GAG) studies in research settings: Specialized labs may measure GAG structure to support a linkeropathy diagnosis. Monarch Initiative
Basic labs (nutrition, infection screens): Identify correctable problems that can worsen outcomes (e.g., dehydration, infection). (General neonatal care best practice.)
Pathology review if surgery occurs: Tissue from tendon or bone surgery can show matrix abnormalities typical of connective-tissue disorders. Monarch Initiative
D) Electrodiagnostic tests
Electrocardiogram (ECG): Records the heart’s electrical activity to detect rhythm or conduction issues in babies with suspected heart defects. United Arab Emirates University
Electroretinogram (ERG) in select cases: Measures retinal function if vision problems seem worse than the front-of-eye changes alone. (Used case-by-case in pediatric eye disease.)
EEG if seizures are suspected: Checks brain electrical activity if there are concerning episodes. (General neonatal neurology practice.)
E) Imaging tests
Prenatal ultrasound: Often shows growth restriction and limb/joint positioning problems before birth. malacards.org
Postnatal skeletal survey (X-rays of the whole skeleton): Documents bone shape, joint positions, and spine changes to guide care. malacards.org
Echocardiogram (heart ultrasound): Looks for structural heart defects that may need treatment. United Arab Emirates University
Ocular imaging (anterior-segment OCT/UBM when feasible): Maps the front of the eye to plan surgery or other eye care.
Brain MRI if clinically indicated: Evaluates brain and eye connections in complicated cases. (General pediatric genetics practice.)
Spine imaging (X-ray/MRI): Assesses vertebral shape and curves for future orthopedic planning. malacards.org
Chest X-ray: Reviews chest wall shape and lung expansion in babies with breathing problems. (General neonatal care practice.)
Non-pharmacological treatments
Because there is no proven disease-modifying drug, supportive, comfort-focused, and preventive care are the cornerstones. Many babies are fragile; the goal is to maximize comfort and safety and avoid invasive steps that do not change outcomes.
NICU team-based supportive care: warm environment, gentle handling, careful positions to protect joints and airway, and family-centered decisions.
Safe airway positioning for micrognathia (side-lying/prone in monitored settings) to reduce obstruction and improve breathing/feeding safety.
Feeding support: lactation guidance, paced feeds, thickened feeds if aspirating, and early speech-swallow therapy; tube feeding when needed for safety and growth. NCBI
Physiotherapy for contractures: gentle daily range-of-motion, short holds, and positioning to maintain joint comfort and prevent skin injury; avoid forceful stretch. PMC
Serial casting for clubfoot (if the infant is stable): gradual weekly casts (Ponseti method) to improve foot position and comfort; it can reduce later surgery needs in survivors.
Custom splints/orthoses for hands/wrists/ankles to maintain neutral positions, reduce pain, and slow contracture return; worn many hours/day with skin checks. Royal Children’s Hospital+1
Night splinting after casting to maintain gains, balanced with free-movement time to support development. PMC
Gentle positioning devices (rolled towels/soft supports) to prevent pressure areas and help neutral limb alignment.
Eye surface protection: frequent preservative-free lubricants and moisture shields to protect cloudy/dry corneas and reduce infection risk.
Infection-prevention bundle: hand hygiene, vaccination of household contacts, smoke-free home, and early care for cough/fever to lower pneumonia risk. NCBI
Bone health measures: adequate calcium/vitamin D intake, sunlight exposure per pediatric guidance, and minimal traumatic handling to limit fractures.
Skin care around splints/casts: daily inspection and barrier creams to avoid sores.
Pain-minimizing handling: swaddling, non-nutritive sucking, skin-to-skin care when safe, dim lights/quiet to reduce stress.
Respiratory physiotherapy (when infection occurs): gentle chest physiotherapy, suctioning, and humidified air per NICU protocol.
Developmental care: age-appropriate soothing, positioning for visual engagement, caregiver voice and touch to support bonding.
Family genetic counseling: explain autosomal recessive inheritance and future pregnancy options (carrier testing; if a causative variant is found). UniProt
Palliative care partnership: align medical plans with the family’s goals; focus on comfort and dignity given the high risk of early death. Genetic Rare Disease Center
Advance care planning: discuss resuscitation choices and hospital-to-home supports early and compassionately.
Vision services (low-vision/early intervention) in any child who survives beyond infancy and has persistent corneal issues.
Care coordination: social work, home nursing, transport planning, and caregiver training for safe feeding and positioning.
Drug treatments
There is no specific medicine that corrects Al-Gazali syndrome. Medicines are used to treat symptoms or complications (pain, infection, reflux, eye surface dryness). Doses in fragile neonates must be individualized by the treating team; ranges below are standard references to show typical practice, not personal medical advice.
Acetaminophen (paracetamol) — for mild pain/fever. Class: analgesic/antipyretic. Typical neonatal dose: 10–15 mg/kg per dose orally/rectally every 6 hrs (max daily 50–75 mg/kg depending on age; NICU may use 20 mg/kg loading). Purpose: comfort, reduce fever. Mechanism: central COX inhibition. Side effects: liver toxicity if overdosed. Medscape+2PMC+2
Topical ocular lubricants — for corneal protection. Class: tear substitutes. Dose/time: frequent drops/gel as needed. Mechanism: barrier/hydration. Side effects: temporary blur.
Oral vitamin D — Class: vitamin. Common dose: per pediatric guidance (e.g., 400 IU/day in many infants). Purpose: bone health in osteopenia risk. Mechanism: calcium absorption. Side effects: high-dose toxicity if misused.
Calcium supplements — Class: mineral. Dose: individualized if dietary intake is low. Purpose: support bone mineralization. Side effects: constipation.
Gentle laxatives (e.g., glycerin suppositories) — Class: stool softeners. Purpose: reduce straining around casts/splints. Side effects: local irritation.
Antireflux therapy (e.g., alginate or H2 blocker if clearly indicated) — reduces reflux and aspiration risk. Mechanism: acid suppression or raft barrier. Side effects: vary by class.
Broad-spectrum antibiotics for pneumonia/sepsis (empiric) — e.g., ampicillin plus gentamicin per NICU protocols. Purpose: treat serious infection. Typical neonatal ranges: ampicillin often 50–100 mg/kg IV every 6–12 hrs; gentamicin 4–5 mg/kg IV with interval by gestational/postnatal age (q24–48h). Side effects: gentamicin ototoxicity/nephrotoxicity (need monitoring). NICU Guidelines+3healthcare.uiowa.edu+3PMC+3
Topical antibiotic eye drops when corneal epithelial defects occur — prevent keratitis. Side effects: local irritation.
Nebulized saline — helps airway clearance in infections. Side effects: cough.
Opioid analgesia (e.g., low-dose morphine in NICU) — for severe pain only under specialist oversight. Side effects: respiratory depression, constipation.
Antipyretics/analgesic rotation — acetaminophen scheduling as tolerated to limit opioid use. Medscape
Iron supplementation if iron-deficiency anemia develops (individualized dose). Side effects: GI upset.
Prophylactic vitamin A in preterm settings (per unit policy) — supports epithelial health; not universal.
Bronchodilators (trial during wheezy illness) if helpful; discontinue if no benefit.
Topical barrier creams to protect skin under splints/casts.
Thickening agents in feeds when aspiration risk is documented and the team approves.
Antifungals if oral thrush appears on antibiotics or tube feeds.
Acyclovir if neonatal HSV is suspected (standard NICU practice for sepsis-like illness with risk). Mechanism: viral DNA polymerase inhibitor. Side effects: kidney effects; dosing is weight/age-based.
Diuretics (rarely, if fluid overload accompanies respiratory illness) — close monitoring.
Ophthalmic anti-glaucoma drops (only if an eye specialist documents raised pressure) — class/mechanism varies (beta-blocker, CAI). Use with extreme caution in infants.
Important: dosing and timing must be set by the treating neonatology/ophthalmology/orthopedics team. The ranges cited are examples from pediatric references, not prescriptions for an individual child. Medscape+2healthcare.uiowa.edu+2
Dietary molecular supplements
Supplements do not cure Al-Gazali syndrome. Use only with clinician approval to avoid interactions or aspiration risk.
Vitamin D (bone mineralization; see above).
Calcium citrate (supports bone; gentler on stomach).
Phosphate (if deficient) (bone matrix; only if labs show low).
Protein-fortified infant feeds (adequate calories for growth).
Omega-3 fats (DHA/ARA in infant formulas) (eye/brain structural lipids).
Probiotics (NICU-approved strains) (may reduce some infections/NEC risk in select settings; policy-dependent).
Multivitamin drops (fill gaps when intake is low).
Zinc (wound/skin integrity for devices/splints; avoid excess).
Selenium (antioxidant enzymes; only if deficient).
Electrolyte-balanced oral rehydration during mild illness (if safe by mouth) to prevent dehydration.
Hard immunity booster / regenerative / stem-cell drugs
There are no proven “immunity boosters,” regenerative chemicals, or stem-cell drugs that treat or reverse Al-Gazali syndrome. Experimental cell or gene therapies have not been established for this condition. The safest, honest plan is supportive care plus future family planning (carrier testing; prenatal or preimplantation genetic testing once a variant is known). Any proposals you see online for “stem-cell cures” in this disease space lack clinical proof and can expose infants to harm. Genetic Rare Disease Center+1
Surgeries
Surgery is not routine because many infants are too fragile and surgery does not change the underlying disease. Procedures are considered case-by-case if a child is strong enough and the expected benefit is meaningful.
Achilles tenotomy (after serial casting for clubfoot) — a tiny cut to lengthen the tendon so the foot stays in the corrected position; improves brace fitting and comfort.
Posteromedial release for clubfoot (later) — more extensive soft-tissue release if casting fails in a survivor; improves foot plantigrade position.
Tarsal tendon lengthening or capsulotomy — to reduce severe foot/wrist contractures that block care or cause pain.
Ocular procedures (e.g., corneal surface repair or glaucoma surgery) — considered by pediatric cornea/glaucoma specialists if vision or pain issues demand it.
Gastrostomy tube placement — only if repeated aspiration/poor growth continues despite safe feeding aids and if overall prognosis and family goals support it.
Prevention points
Genetic counseling for families after one affected child; discuss autosomal recessive risk (25% each pregnancy when both parents are carriers). UniProt
Carrier testing of parents and at-risk relatives when the familial variant is identified. NCBI
Prenatal diagnostic options in future pregnancies (CVS/amniocentesis) once a variant is known. NCBI
Preimplantation genetic testing (PGT-M) with IVF in families who choose it.
Healthy pregnancy supports (folate, nutrition, no smoking/alcohol) — general fetal well-being.
High-risk obstetric care with targeted fetal ultrasound to monitor movement and limb position.
Delivery in a center with NICU and pediatric surgical/eye support when Al-Gazali or a similar condition is suspected.
Household vaccination and hand hygiene to protect fragile infants from infections.
Safe-sleep education and positioning to lower airway obstruction risk.
Early palliative-care discussions so care matches family values from the start.
When to see doctors
During pregnancy: reduced fetal movement, severe clubfoot on scan, or polyhydramnios → see maternal-fetal medicine and genetics. NCBI
After birth: any breathing difficulty, bluish color, poor feeding, choking/coughing with feeds, fever, or unusual sleepiness → urgent NICU/ER evaluation.
Eyes: signs of corneal irritation (redness, tearing, blinking, light sensitivity) or a white cornea → pediatric ophthalmology urgently. NCBI
Bones/joints: swelling, warmth, or sudden pain (possible fracture or skin pressure injury under a cast/splint) → immediate care. NCBI
What to eat and what to avoid
Breast milk (preferred) or appropriate infant formula with calorie adjustments guided by the team.
Frequent, small, paced feeds to lower aspiration risk; use thickener only if recommended by clinicians.
Vitamin D per pediatric guidance; add calcium if intake is low.
Upright or side-lying feeding positions; keep baby upright after feeds when safe.
Avoid force-feeding and stop feeds if coughs, color change, or breathing trouble occur.
Avoid unapproved herbal products (unknown safety in neonates).
Hydration during illness using clinician-approved methods.
Consider fortifiers if growth is poor (under dietitian guidance).
Protect against reflux triggers (overfeeding, tight diapers immediately after feeds).
Caregiver training on tube-feeding if a tube is placed.
FAQs
Is Al-Gazali syndrome the same as “Al-Gazali skeletal dysplasia”?
No. They are different. “Al-Gazali skeletal dysplasia” is now linked to ADAMTSL2 and represents a lethal skeletal disorder spectrum; Al-Gazali syndrome described here has a broader joint-eye-bone picture and uncertain genetics, with B3GALT6 phenocopies reported. Oxford Academic+1How is it inherited?
Usually autosomal recessive; parents are healthy carriers. UniProtCan we test for it?
Yes—clinicians may order gene panels/exome to look for known genes in similar conditions; some labs list Al-Gazali syndrome and test genes like B3GALT6 among others. NCBIIs there a cure?
Not currently. Treatment is supportive and focuses on comfort and preventing complications. Genetic Rare Disease CenterCan contractures be improved?
Gentle physiotherapy, splinting, and sometimes serial casting can improve comfort and positioning; results vary. PMC+1Are surgeries common?
Only in select survivors when benefits clearly outweigh risks. Many infants are too fragile for surgery.What about pain control?
Acetaminophen is first-line; stronger medicines are used only under close monitoring. MedscapeDo eye problems threaten vision?
They can. Corneal care and early ophthalmology input are important; surgery is rare and highly specialized. NCBIWhat is the life expectancy?
Reports describe early lethality in many cases, but every child is unique. The care team will discuss realistic goals. Genetic Rare Disease CenterCould infections be deadly?
Yes, especially pneumonia. Prevention and early treatment matter. NCBICan supplements help?
Supplements support nutrition/bone, but they do not treat the underlying disease.Should we enroll in research?
Rare-disease registries and genetics studies can help families and science; your team can guide you.Is prenatal diagnosis possible next time?
Yes, when a familial variant is identified; options include CVS, amniocentesis, or PGT-M. NCBIHow do we avoid pressure sores from splints/casts?
Daily skin checks, proper padding, and scheduled breaks; tell your team about any redness. Royal Children’s HospitalWhere can we learn more?
Trusted summaries: GARD, MedGen, Monarch/MONDO, and reputable rare-disease catalogs. Genetic Rare Disease Center+2NCBI+2
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Last Updated: September 11, 2025.
