Synophthalmia (pronounced sin-off-THAL-mee-ah) is a very rare and severe birth defect in which the two developing eyes fail to separate and instead grow together in the midline of the face. The result is a single eye-like structure or two partly fused eyeballs sharing one orbit. Synophthalmia sits on the same spectrum as cyclopia and alobar holoprosencephaly, conditions that arise when the front part of the embryonic brain (the prosencephalon) does not divide properly early in pregnancy. Because the brain and face form together, failure of brain division also disturbs eye, nose and upper-jaw formation; most babies are therefore miscarried, stillborn, or die shortly after birth. WikipediaPMC
Synophthalmia is a very rare and severe birth defect in which the two eyes are fused into a single eye or appear extremely close together, often with other facial midline malformations. It is usually part of the spectrum of cyclopia and reflects the most extreme form of holoprosencephaly (HPE)—a condition where the embryonic brain fails to divide properly into left and right halves early in pregnancy (around weeks 3–4). Because the forebrain (prosencephalon) does not split, the facial features that normally develop symmetrically also fuse, producing a single midline eye field or very closely set eyes, often with absence of a normal nose or presence of a proboscis above the fused eye. Most infants with synophthalmia are either stillborn or die very soon after birth due to the underlying brain malformation and associated organ dysfunction. PMCMDPICleveland Clinic
Holoprosencephaly and its facial manifestations like synophthalmia result from disruptions in embryonic signaling pathways (e.g., Sonic Hedgehog), genetic mutations, or environmental insults during early development. The severity varies, but synophthalmia represents one of the most severe. MDPI
Early medical writings sometimes call the disorder “cyclocephaly” or “fused-eye holoprosencephaly.” The syndrome is universally fatal, usually recognised on prenatal ultrasound or at birth, and its true frequency is estimated at about 1 in 16 000 to 1 in 100 000 pregnancies, though many cases end in unrecorded early miscarriage. PMC
Types and anatomical variants
- Classical (complete) synophthalmia.
Here the two eyes fully merge into a single globular structure with one shared lens and retina. The nasal structures are usually absent and a tubular proboscis—a skin-covered, non-functioning “false nose”—may sit above the eye. PMCLippincott Journals - Incomplete (partial) synophthalmia.
The globes are only partly fused: two corneas may be visible but share one bony orbit and one set of eyelids. Remnants of a nose, cleft lip, or other midline defects are common. Lippincott Journals - Association with holoprosencephaly sub-types.
Pathologists classify cases by the underlying brain malformation (alobar, semilobar or lobar holoprosencephaly). Synophthalmia almost always co-exists with the most severe “alobar” form, where the cerebral hemispheres never split. Radiopaedia - Spectrum concept.
Cyclopia (a single median eye) is the extreme end; synophthalmia represents the next-most severe fusion; milder relatives include severe hypotelorism (very close-set eyes) and median facial clefts. PMC
Main causes
Trisomy 13 (Patau syndrome). An extra copy of chromosome 13 disrupts dozens of genes guiding early head formation; up to 70 % of cyclopia or synophthalmia autopsies reveal this aneuploidy. Obstetrics & GynecologyPMC
Trisomy 18 (Edwards syndrome). Although less common than trisomy 13, this chromosome error is another recognised driver of holoprosencephaly and fused-eye defects. PMC
Triploidy. Having a full extra set of chromosomes (69,XXX/XXY) severely disturbs brain segmentation and can yield midline eye fusion. PMC
Pathogenic variants in the SHH gene. Sonic hedgehog is the master signal telling the embryonic face and forebrain to separate; loss-of-function mutations are a leading single-gene cause. PMC
ZIC2 mutations. This zinc-finger transcription factor cooperates with SHH. Certain missense and truncating variants produce severe ocular and forebrain fusion. PMC
SIX3 mutations. SIX3 activates eye-field genes; pathogenic variants derail optic-cup splitting, ending in synophthalmia in animal models and humans alike. PMC
GLI2 and hedgehog-pathway defects. GLI2 interprets SHH signals; mutations mimic SHH loss, giving similar fused-eye phenotypes. MDPI
FGF8 and FGFR1 variants. Disrupted fibroblast-growth-factor signalling weakens midline patterning, allowing orbits to merge. MDPI
Pregestational maternal diabetes. High glucose levels alter oxidative stress and SHH pathways; diabetic embryopathy increases holoprosencephaly risk nearly ten-fold. PMCAnnex Publishers
Alcohol exposure in early pregnancy. Ethanol directly suppresses SHH expression; heavy first-trimester drinking is a well-proven teratogen for fused-eye malformations. Cleveland ClinicWiley Online Library
Isotretinoin (retinoic-acid) therapy. Excess vitamin A derivatives overstimulate retinoid receptors, collapsing midline development even at standard acne-medication doses. Cleveland Clinic
Anticonvulsants (e.g., valproic acid, carbamazepine). These drugs interfere with folate metabolism and histone deacetylation during neural-tube closure, occasionally producing synophthalmia. Cleveland Clinic
Lithium carbonate. Mood-stabiliser use very early in gestation can perturb Wnt signalling and has been linked to holoprosencephaly spectrum defects. EyeWiki
Cyclopamine from Veratrum californicum. In sheep, grazing on this plant on gestational day 14 blocks SHH, generating classic synophthalmia; human exposure to Hedgehog inhibitors shows similar risk. PubMed
Mycotoxins and other food-borne toxins. Mold toxins such as fumonisins act as environmental Hedgehog antagonists and are under study in human holoprosencephaly clusters. Cleveland Clinic
Maternal TORCH infections (toxoplasmosis, rubella, CMV, herpes). Viral disruption of early neuroectoderm can culminate in eye-brain malformations. EyeWiki
Cigarette smoking and nicotine. Vascular and oxidative insults from tobacco raise the odds of forebrain and ocular fusion anomalies. Annex Publishers
High maternal fever or hot-tub hyperthermia. Sustained core temperatures >39 °C around weeks 3-4 post-conception impair Shh-mediated neurulation. MSJ Online
Folate deficiency or poor multivitamin use. Low folic-acid intake removes a protective effect and allows other risk factors to trigger holoprosencephaly. Wiley Online LibraryMDPI
Complex multifactorial gene–environment interaction. In many pregnancies a mild genetic variant plus a modest environmental hit together cross the threshold for synophthalmia, explaining sporadic, non-syndromic cases. PMC
Symptoms and clinical features
Single midline eye or partly fused eyes. The hallmark—a central ocular structure—is usually obvious on scan or at birth. PMC
Proboscis above the eye. A skin tube with one blind nostril often replaces the normal nose. Lippincott Journals
Absent or very under-developed nose (arhinia). Babies lack nasal passages, making breathing impossible without intervention. PMC
Severe hypotelorism. If fusion is incomplete, the two corneas sit abnormally close together. EyeWiki
Median cleft lip and/or palate. Midline fusion failure of facial processes leaves a central gap in the upper lip or palate. Lippincott Journals
Microcephaly. Because the forebrain never divides, head circumference is markedly small. PMC
Global developmental delay (in rare survivors). Infants who live for weeks to months show profound motor and cognitive impairment. PubMed
Seizures. Disorganised cortical tissue predisposes to early-onset epilepsy. PubMed
Instability of temperature and heart rate. Brainstem dysgenesis leads to poor autonomic control. PubMed
Feeding and swallowing difficulties. Lack of coordinated suck–swallow reflex plus oral clefts makes nutrition challenging. Orpha
Abnormal eye movements or fixed gaze. Cranial-nerve nuclei are malformed, so extra-ocular muscles may not work symmetrically. MDPI
Vision loss. Even if two retinas exist, optical pathways are malformed, leaving functional blindness. MDPI
Hydrocephalus. Cerebrospinal fluid may accumulate because midline brain cavities are fused. Orpha
Endocrine abnormalities (e.g., low cortisol or thyroid hormone). Pituitary insufficiency arises from basal forebrain maldevelopment. Children’s Hospital Colorado
Short survival or stillbirth. Most affected fetuses die before or soon after delivery because respiration and circulation cannot be sustained. PMC
Further diagnostic tests
Physical-examination tools
Detailed craniofacial inspection. Neonatologists look for a single orbit, absent nose, or proboscis to clinch the bedside diagnosis. PMC
Head circumference measurement. Serial plotting confirms microcephaly and guides neuro-developmental counselling. PMC
Primitive-reflex assessment. Absent rooting or sucking hints at brainstem dysfunction. PubMed
Respiratory pattern observation. Apnoea or erratic breathing signals central autonomic failure. PubMed
Manual / bedside functional tests
Pupillary light reflex. A dim or absent response supports optic-nerve maldevelopment. MDPI
Extra-ocular muscle testing. Attempting to move a visible globe reveals restrictive fusion and cranial-nerve palsy. MDPI
Oral cavity palpation. Feeling the palate detects a hidden median cleft that imaging might overlook. Lippincott Journals
Chest auscultation for murmurs. Synophthalmia can co-occur with midline heart defects; a handheld exam directs echocardiography. Orpha
Laboratory & pathological tests
Standard karyotype (G-banding). Detects trisomy 13, 18, triploidy, or large translocations in over half of cases. Obstetrics & GynecologyNCBI
Chromosomal microarray. Picks up sub-microscopic deletions or duplications affecting SHH-pathway genes. Invitae
Targeted gene panel (e.g., SHH, ZIC2, SIX3, FGFR1). Clarifies single-gene aetiology and helps parents with recurrence risk. Blueprint Genetics
Whole-exome or genome sequencing. Reserved for negative panel results in research or highly specialised centres. OHSU Knight Diagnostic Laboratories
TORCH serology. Screens mother and infant for infections that mimic or compound holoprosencephaly. EyeWiki
Maternal HbA1c. Confirms poorly controlled diabetes as a modifiable risk factor. PMC
Electrodiagnostic tests
Electroencephalogram (EEG). Captures subclinical seizures and assesses cortical organisation. PubMed
Visual-evoked potentials (VEP). Determines if any optic pathway function exists behind the fused or malformed globes. MDPI
Brainstem auditory-evoked responses (BAER). Holoprosencephaly can impair hearing; this test evaluates auditory-nerve integrity. Orpha
Imaging tests
Prenatal ultrasound. At 11-14 weeks, sonographers may see a single midline orbit and a monoventricular brain cavity—often the first clue. AJR American Journal of RoentgenologyCleveland Clinic
Fetal or neonatal MRI. Provides high-resolution views of brain architecture, confirms alobar holoprosencephaly, and guides delivery planning. American Journal of NeuroradiologyPMC
Computed tomography (CT). In ex-utero autopsy or post-mortem settings, CT delineates bone fusion and orbital anatomy for counselling and research. PMC
Non-Pharmacological Treatments
Each item below is a non-drug intervention, with its description, purpose, and mechanism or rationale.
Genetic Counseling
Description: A trained genetics professional evaluates family history, explains recurrence risk, and interprets genetic tests.
Purpose: To help parents understand the cause, future pregnancy risks, and available reproductive options.
Mechanism: Provides information-based decision support; identifies whether parents carry mutations or if the case was sporadic. HPE Research
Prenatal Screening and Early Detection (Ultrasound / MRI)
Description: Detailed fetal anatomy scans and fetal MRI in high-risk pregnancies or when anomalies are suspected.
Purpose: Early identification of synophthalmia/holoprosencephaly to prepare medical teams and counsel families.
Mechanism: Imaging detects lack of forebrain division and facial midline fusion, enabling anticipatory care. PMC
Palliative Care Planning
Description: Multidisciplinary support focused on comfort, family goals, and quality of life when prognosis is poor.
Purpose: Aligns care with family values, manages symptoms, supports emotional needs.
Mechanism: Integrates medical, psychosocial, and spiritual support to reduce suffering. StatPearls
Feeding and Swallowing Support (Speech/Occupational Therapy)
Description: Assessment and management of feeding difficulties via therapists trained in pediatric dysphagia.
Purpose: Prevent aspiration, ensure nutrition in infants with clefting or neurologic impairment.
Mechanism: Techniques include specialized feeding positions, pacing, and adaptive devices. StatPearls
Physical Therapy / Early Developmental Therapy
Description: Structured exercises and activities to maximize motor development despite brain anomalies.
Purpose: Improve strength, tone, and functional movement in infants with hypotonia or motor delay.
Mechanism: Neurodevelopmental stimulation takes advantage of plasticity to optimize function. ResearchGate
Occupational Therapy
Description: Support for fine motor skills, daily care adaptations, and sensory integration.
Purpose: Help children adapt to limitations and improve self-care or caregiver-assisted care.
Mechanism: Task-specific training, environmental modification, and assistive device recommendations. ResearchGate
Vision Support / Low Vision Services
Description: Ophthalmologic evaluation and adaptive visual aids if any residual vision exists.
Purpose: Maximize remaining vision, support visual development where possible.
Mechanism: Early assessment identifies treatable causes and provides tools (magnifiers, stimuli) to engage visual pathways. StatPearls
Endocrine Evaluation & Support (non-pharmacological monitoring)
Description: Regular clinical monitoring for signs of pituitary/ hypothalamic dysfunction before hormone therapy decisions.
Purpose: Early detection of growth, thyroid, adrenal, or diabetes insipidus issues.
Mechanism: Clinical surveillance triggers timely lab testing and later interventional therapy. PMC
Seizure Safety Education and Monitoring
Description: Teaching caregivers seizure recognition, safe positioning, and when to seek help.
Purpose: Reduce injury, ensure rapid response, and recognize triggers (e.g., dehydration).
Mechanism: Empowered caregivers minimize secondary harm from epilepsy, a common comorbidity. PMC
Respiratory Support and Airway Assessment
Description: Evaluation for upper airway obstruction, provision of oxygen, suctioning, or non-invasive breathing support.
Purpose: Maintain adequate oxygenation in infants with brainstem dysregulation or facial structural compromise.
Mechanism: Early recognition of apnea or obstruction prevents hypoxic injury. StatPearls
Nutritional Counseling & Support
Description: Dietitian involvement to ensure growth despite feeding challenges.
Purpose: Prevent malnutrition, support immune function and tissue healing.
Mechanism: Customized caloric plans, alternative feeding (e.g., G-tube planning), micronutrient optimization. ResearchGate
Family Psychological Support / Therapy
Description: Mental health support for parents and siblings coping with a severe diagnosis.
Purpose: Reduce anxiety, grief, and burnout.
Mechanism: Counseling, support groups, trauma-informed therapy improve coping and decision-making. StatPearls
Social Work and Care Coordination
Description: Assistance with navigating hospital systems, insurance, home care, and resources.
Purpose: Reduce logistical burden on families.
Mechanism: Case management connects families to services (equipment, financial aid). StatPearls
Early Intervention Programs
Description: State or community developmental support services starting in infancy.
Purpose: Address delays proactively to maximize developmental potential.
Mechanism: Regular assessments and targeted therapies (speech, motor, cognitive) based on individualized plans. ResearchGate
Hearing Evaluation and Support
Description: Audiology screening because facial anomalies can accompany ear/cranial nerve issues.
Purpose: Identify hearing loss early to support communication development.
Mechanism: Hearing aids or alternative communication strategies introduced when needed. StatPearls
Caregiver Training for Home Medical Care
Description: Teaching tube feeding, seizure first aid, and use of adaptive equipment.
Purpose: Safe home transition and reduced emergency visits.
Mechanism: Hands-on training increases caregiver competence and child safety. StatPearls
Ethics Consultations / Shared Decision Making
Description: Structured discussions about goals of care for severely affected infants.
Purpose: Align care with family values, particularly around life-sustaining interventions.
Mechanism: Facilitate transparent communication and reduce decisional conflict. StatPearls
Advance Care Planning
Description: Documenting in writing the extent of interventions desired if prognosis is poor.
Purpose: Prevent confusion during acute crises.
Mechanism: Templates and guided conversations create clear directives. StatPearls
Support Groups / Peer Connection
Description: Linking families with others who have faced similar rare diagnoses.
Purpose: Reduce isolation, share practical tips, emotional solidarity.
Mechanism: Peer mentoring and online communities offer lived-experience advice. StatPearls
Care Pathway Standardization / Multidisciplinary Clinics
Description: Using predefined care protocols in specialized centers for HPE and midline defects.
Purpose: Ensure consistent, evidence-based, coordinated care.
Mechanism: Multispecialty teams (neurology, genetics, surgery, endocrinology, palliative) reduce fragmentation. Child Neurology Society
Evidence-Based Drug Treatments
Important framing: There is no “cure” drug for synophthalmia itself; therapy is directed at complications (e.g., seizures, hormonal deficits, reflux). Dosing in neonates/infants must be individualized by pediatric specialists; below are typical classes with common drugs, their rationale, and known side effects.
Levetiracetam (Antiepileptic)
Class: Broad-spectrum anticonvulsant.
Dosage: Often starts at 10 mg/kg twice daily, titrated up (neonatal dosing under specialist guidance).
Purpose: Control seizures common in HPE.
Mechanism: Binds SV2A synaptic vesicle protein, modulating neurotransmitter release.
Side Effects: Irritability, somnolence, behavioral changes. PMCMedscape
Carbamazepine (Antiepileptic)
Class: Sodium channel modulator.
Dosage: Weight-based, careful titration; used when partial complex seizures predominate.
Purpose: Seizure control.
Mechanism: Stabilizes inactive sodium channels to reduce neuronal excitability.
Side Effects: Hyponatremia, rash (including rare severe hypersensitivity), liver enzyme elevations. PMC
Hydrocortisone (Hormone Replacement for Secondary Adrenal Insufficiency)
Class: Glucocorticoid.
Dosage: Physiologic replacement varies (e.g., 10–12 mg/m²/day divided).
Purpose: Replace cortisol if hypothalamic-pituitary-adrenal axis is impaired.
Mechanism: Replaces deficient cortisol, stabilizes metabolism and stress response.
Side Effects: Cushingoid features with over-replacement, immune suppression if high doses. PMC
Levothyroxine (Thyroid Hormone Replacement)
Class: Synthetic T4.
Dosage: Neonatal dosing is low then titrated; typically 10–15 mcg/kg/day in congenital hypothyroidism scenarios.
Purpose: Replace thyroid hormone if central hypothyroidism occurs.
Mechanism: Provides T4 for metabolism and brain development support.
Side Effects: Tachycardia or irritability if overdosed. PMC
Desmopressin (for Diabetes Insipidus)
Class: Vasopressin analog.
Dosage: Intranasal or oral microdoses adjusted to urine output and sodium.
Purpose: Control polyuria/polydipsia from central diabetes insipidus (possible with hypothalamic involvement).
Mechanism: Acts on renal V2 receptors to concentrate urine.
Side Effects: Hyponatremia if over-treated. PMC
Omeprazole (Proton Pump Inhibitor)
Class: Acid suppression.
Dosage: Weight-based pediatric dosing (e.g., 0.7–3.5 mg/kg/day).
Purpose: Treat reflux, which can be severe due to hypotonia and feeding dysfunction.
Mechanism: Blocks H+/K+ ATPase in gastric parietal cells reducing acid.
Side Effects: Increased risk of gastrointestinal infections, altered absorption of some nutrients. StatPearls
Antibiotics for Aspiration Pneumonia (e.g., Ampicillin plus Gentamicin when indicated)
Class: Broad-spectrum/combination (based on local guidelines).
Purpose: Treat or prevent pneumonia from recurrent aspiration.
Mechanism: Kill or inhibit bacteria introduced via aspiration.
Side Effects: Nephrotoxicity (gentamicin), allergic reactions. (Standard pediatric care principles apply.) StatPearls
Supplemental Oxygen / Respiratory Support (if considered in medication-like supportive interventions)
Class: Not a drug per se but administered as medical therapy.
Purpose: Correct hypoxia from respiratory instability.
Mechanism: Increases arterial oxygen saturation; may be delivered via nasal cannula or non-invasive support.
Side Effects: Oxygen toxicity if unmonitored (rare at appropriate levels). StatPearls
Antipyretics / Pain Management (e.g., Acetaminophen)
Class: Analgesic/antipyretic.
Dosage: Weight-based (e.g., 10–15 mg/kg per dose).
Purpose: Comfort for procedures or associated illnesses.
Mechanism: Inhibits central prostaglandin synthesis (exact mechanism partly unclear).
Side Effects: Liver toxicity if overdosed. StatPearls
Vitamin and Mineral Replacement (when deficiency is documented)
Class: Micronutrient therapy.
Purpose: Correct documented deficiencies that could worsen neurodevelopment (e.g., vitamin D, iron).
Mechanism: Restores cofactors needed for normal metabolic and neurologic function.
Side Effects: Iron overload if excessive, hypervitaminosis if unmonitored. ResearchGate
Dietary / Molecular Supplements
Important: For an affected infant, supplements must be guided by a physician; many listed here refer to prevention in pregnancy and optimization of early development in at-risk pregnancies.
Folic Acid (Vitamin B9)
Dosage: At least 400–800 mcg daily preconception and during early pregnancy (higher if risk factors).
Function: Supports neural tube closure and proper midline development.
Mechanism: Donates methyl groups in DNA synthesis and repair, critical during rapid cell division.
Note: Strong evidence in reducing neural tube defects; may lower some risk of midline defects. MedLink
Choline
Dosage: ~450 mg/day in pregnancy (varies by guideline).
Function: Supports brain development and neurotransmitter synthesis.
Mechanism: Precursor to acetylcholine and methyl group metabolism affecting gene expression.
Evidence: Emerging data supports its role in neurodevelopmental outcome optimization. MDPI
Vitamin B12
Dosage: ~2.6 mcg/day in pregnancy (higher if deficiency or vegetarian).
Function: Works with folate in DNA synthesis and neurological health.
Mechanism: Cofactor in methylation and myelin formation.
Evidence: Deficiency in early pregnancy can impair neural development. MedLink
Iodine
Dosage: ~150 mcg/day (pregnancy needs ~220 mcg, often via iodized salt or prenatal vitamins).
Function: Thyroid hormone synthesis; critical for brain development.
Mechanism: Iodine is incorporated into T3/T4; deficiency leads to cretinism and neurodevelopmental delay.
Evidence: Maternal iodine deficiency disrupts early neurodevelopment. Cleveland Clinic
DHA (Docosahexaenoic Acid, Omega-3)
Dosage: 200–300 mg/day during pregnancy and lactation.
Function: Structural component of neuronal membranes; supports visual and cognitive development.
Mechanism: Integrates into phospholipid bilayer, modulates inflammation and synaptic plasticity.
Evidence: Maternal DHA linked to better neurodevelopmental outcomes. MDPI
Vitamin D
Dosage: Often 600 IU/day for pregnant women, adjusted if deficient.
Function: General immune and neurodevelopmental support.
Mechanism: Regulates gene expression including neurotrophic factors.
Evidence: Low maternal vitamin D associated with various developmental issues. ResearchGate
Zinc
Dosage: ~11 mg/day in pregnancy.
Function: Enzyme cofactor, cell division, and DNA repair.
Mechanism: Participates in transcription factor regulation, essential during embryogenesis.
Evidence: Deficiency correlates with congenital malformations in animal and some human studies. MDPI
Magnesium
Dosage: ~350–360 mg/day (dietary; supplement if low).
Function: Cellular energy, neuromuscular stability.
Mechanism: Cofactor in ATP reactions, modulates NMDA receptors.
Evidence: Supports fetal growth; severe deficiency can impair development. ResearchGate
Antioxidant Support (e.g., Vitamin C / E) – with caution
Dosage: Within recommended dietary allowances (e.g., Vitamin C ~85 mg/day pregnancy).
Function: Neutralize oxidative stress during development.
Mechanism: Scavenge free radicals that can damage DNA/cells.
Evidence: Some association of oxidative stress with developmental anomalies; routine high-dose supplementation not routinely recommended without deficiency. ResearchGate
Probiotics (Maternal gut health)
Dosage: As per studied strains (e.g., Lactobacillus rhamnosus GG doses vary).
Function: Modulate maternal immune milieu; emerging data on influence in development.
Mechanism: Gut microbiome interacts with systemic inflammation and nutrient absorption.
Evidence: Early research suggests maternal microbiome may have indirect effects on neurodevelopmental risk. ResearchGate
Note: Some supplements (e.g., high-dose Vitamin A) are harmful in pregnancy and must be avoided. Cleveland Clinic
Regenerative / Stem Cell / “Hard Immunity” / Investigational Approaches
Important framing: There is no approved regenerative or stem cell treatment for synophthalmia or holoprosencephaly. What follows are research-stage or experimental approaches primarily in related central nervous system injury contexts; their relevance to synophthalmia is theoretical and unproven. Families should be warned about unregulated “stem cell clinics.” PubMedFrontiersPMCMedical XpressResearch at UMC Utrecht
Human Neural Stem Cells (hNSCs)
Functional Goal: Replace or support damaged neural tissue, promote neuroprotection.
Mechanism: Delivered cells may secrete growth factors, modulate inflammation, and integrate into circuits in preclinical models.
Status: Early-phase trials in brain injury; no clinical evidence for congenital structural malformations like HPE/synophthalmia. Dosing is experimental and varies by protocol. PubMedFrontiers
Mesenchymal Stem/Stromal Cells (MSCs)
Functional Goal: Immunomodulation and support of endogenous repair.
Mechanism: Secrete cytokines, reduce inflammation, promote survival of existing neurons.
Status: Investigated in stroke and TBI; no established use in midline developmental disorders. Medical Xpress
Induced Pluripotent Stem Cell-Derived Neural Progenitors
Functional Goal: Patient-specific generation of neural precursors for potential future repair.
Mechanism: Reprogrammed cells differentiate into neural lineages; theoretical future application to developmental defects.
Status: Laboratory stage; risks include tumorigenicity and incomplete integration. ScienceDirect
Umbilical Cord Blood Stem Cell Infusions
Functional Goal: Provide trophic support and potential neurodevelopmental modulation.
Mechanism: Mixed progenitors may support existing neural networks through paracrine effects.
Status: Trialed in other neurodevelopmental disorders; not substantiated for synophthalmia. Research at UMC Utrecht
Neurotrophic Factor Modulation (e.g., BDNF mimetics in research)
Functional Goal: Enhance survival and plasticity of neurons during early life.
Mechanism: Boost signaling pathways that support neuronal differentiation and connectivity.
Status: Experimental; no approved drugs and untested for congenital midline structural defects. (Inference from regenerative neurobiology literature.) Frontiers
Gene Therapy Targeting Signaling Pathways (Theoretical)
Functional Goal: Correct underlying developmental signaling defects (e.g., SHH pathway).
Mechanism: Delivery of functional genes or modulation of pathway activity during embryogenesis.
Status: Purely theoretical for HPE/synophthalmia in humans; enormous technical, ethical, timing, and safety barriers. MDPI
Summary: None of these are current clinical standards for synophthalmia. Families should avoid paid “miracle” stem cell offerings without rigorous trial data. FrontiersMedical Xpress
Surgical / Procedural Interventions
Ventriculoperitoneal (VP) Shunt Placement
Procedure: Surgical insertion of a catheter to drain excess cerebrospinal fluid from ventricles to abdomen.
Why: Hydrocephalus is common in severe forebrain malformations; shunt reduces intracranial pressure, preventing further brain injury and enabling symptom control. StatPearls
Feeding Tube Placement (Gastrostomy Tube / G-tube)
Procedure: Surgical or endoscopic creation of a direct stomach feeding access.
Why: Bypass unsafe oral feeding in infants with swallowing difficulty or aspiration risk to ensure adequate nutrition. StatPearls
Airway Management Procedures (e.g., Tracheostomy)
Procedure: Surgical opening in the neck to secure an airway.
Why: Severe breathing compromise from brainstem dysfunction or obstructed anatomy may require secure long-term airway support. StatPearls
Craniofacial Evaluation / Reconstructive Consultation
Procedure: Detailed surgical assessment; on selected occasions, limited reconstruction for clefting or other associated defects.
Why: Improve feeding, airway patency, or (rarely) cosmetic/functional aspects in less lethal forms; often part of multidisciplinary planning. StatPearls
Supportive Comfort Procedures (e.g., minor wound care, pressure area protection)
Procedure: Non-invasive procedural care to prevent secondary harm, such as skin protection or minor drainage.
Why: Infants with limited mobility and neurologic impairment are at risk of pressure injuries and infections; these prevent complications. StatPearls
Prevention Strategies
Preconception Folic Acid Supplementation
Why: Reduces risk of neural tube and possibly midline brain defects. MedLink
Maternal Glycemic Control (Diabetes Management)
Why: Poorly controlled diabetes in early pregnancy increases congenital anomaly risk, including HPE spectrum. Cleveland Clinic
Avoidance of Known Teratogens
Why: Drugs like high-dose retinoids, unneeded radiation, alcohol, and some anticonvulsants when not strictly necessary can disrupt early brain patterning. Cleveland Clinic
Genetic Counseling for At-Risk Couples
Why: Identifies parental mutations or previous affected pregnancy history to guide surveillance or reproductive choices. HPE Research
Early Prenatal Ultrasound Screening
Why: Detection of anomalies early can inform care planning or reproductive decisions. PMC
Managing Maternal Obesity and Nutrition
Why: Optimal maternal health reduces developmental stressors; obesity correlates with higher congenital risk in some studies. ResearchGate
Supplementing Essential Micronutrients (Iodine, Choline, B12)
Why: Adequate levels support brain and midline formation; deficiency can potentiate malformations. MedLinkCleveland Clinic
Avoiding Excess Vitamin A
Why: High vitamin A (e.g., isotretinoin) is teratogenic and can cause severe craniofacial defects. Cleveland Clinic
Screening for Underlying Metabolic Syndromes (e.g., Smith-Lemli-Opitz)
Why: Identifying and managing known metabolic contributors preconception or early pregnancy can reduce risk. NCBI
Vaccination and Infection Control in Mother (e.g., prevent TORCH infections)
Why: Some infections early in pregnancy can contribute to congenital anomalies; prevention reduces overall risk. Cleveland Clinic
When to See a Doctor
During pregnancy: If early routine scans show facial or brain midline abnormalities, immediate referral for high-resolution imaging and genetic counseling. PMC
At birth: Any infant born with fused eyes, absent nose or proboscis, abnormal head shape, poor breathing, feeding difficulty, or low tone needs urgent neonatal and neurologic evaluation. StatPearls
Seizures or abnormal movements: Early seizure onset warrants prompt anticonvulsant evaluation. PMC
Failure to feed or gain weight: Nutrition support team involvement (speech/feeding therapy). StatPearls
Signs of endocrine dysfunction: Persistent hypoglycemia, abnormal growth, or dehydration (possible diabetes insipidus) needs endocrinology input. PMC
Developmental delays or lack of expected milestones: Early intervention referral. ResearchGate
Respiratory distress: Breathing problems may reflect brainstem involvement; immediate respiratory/ENT evaluation. StatPearls
What to Eat and What to Avoid
What to Eat (to support healthy early brain/midline development):
Leafy green vegetables, beans, and fortified cereals (folic acid) to supply folate. MedLink
Eggs and liver (in moderate amounts) for choline—important for brain signaling. MDPI
Seafood with low mercury for DHA and iodine (or prenatal supplements). Cleveland Clinic
Dairy, lean meat, or fortified plant alternatives for vitamin B12 and zinc. MedLink
Foods rich in magnesium (nuts, whole grains) and vitamin D (sun exposure, fortified milk) if deficiency risk. ResearchGate
What to Avoid:
Alcohol: Causes direct developmental harm and increases congenital anomaly risk. Cleveland Clinic
Excess vitamin A (e.g., high-dose supplements, isotretinoin): Teratogenic; avoid unless under strict physician guidance. Cleveland Clinic
Uncontrolled high blood sugar / poorly managed diabetes: Increases risk of midline defects. Cleveland Clinic
High-mercury fish: Can harm fetal brain development if overconsumed. (General fetal nutrition guidance.) Cleveland Clinic
Non-prescribed herbal supplements without review: Some have unknown pregnancy safety profiles. ResearchGate
Frequently Asked Questions
What causes synophthalmia?
It is caused by early problems in brain and face development, often from genes, chromosomes, metabolism problems, or harmful exposures in early pregnancy. MDPIHPE ResearchIs there a cure for synophthalmia?
No. There is no cure. Care focuses on comfort, treating complications, and helping the family make decisions. StatPearlsCan synophthalmia be prevented?
Some risk can be reduced by taking folic acid before pregnancy, controlling diabetes, avoiding known harmful drugs, and getting genetic counseling. MedLinkCleveland ClinicWill future pregnancies be affected?
That depends on the underlying cause. If a genetic mutation is found, the risk can sometimes be high; if it was a one-time event, risk might be low. Genetic counseling helps clarify. HPE ResearchHow is synophthalmia diagnosed before birth?
Through detailed prenatal ultrasound and fetal MRI showing the fused eyes and brain changes. PMCWhy do babies with synophthalmia have other problems?
Because the same early developmental failure affects the brain, pituitary gland, feeding, breathing, and other systems. PMCStatPearlsDo all babies with synophthalmia survive?
Most do not survive long after birth due to severe brain malformations. Some less severe related conditions may live longer with supportive care. MDPIWhat treatments are available?
Supportive care: managing seizures, feeding, breathing, hormonal problems, and offering comfort. Surgery is used only for specific needs like feeding tubes or shunts. StatPearlsPMCAre stem cells a cure?
Not currently. Stem cell treatments are experimental and not proven for synophthalmia. Families should be cautious of unproven claims. FrontiersMedical XpressDoes taking folic acid help if I already have a baby with synophthalmia?
It can help future pregnancies, especially combined with full preconception evaluation, because it reduces risk of some birth defects. MedLinkShould I get genetic testing?
Yes. Testing can identify if there is a known gene or chromosomal cause and help guide future planning. HPE ResearchWhat specialists will my child need?
A team: neurologist, geneticist, endocrinologist, feeding specialist, palliative care, neurosurgeon, and others depending on issues. StatPearlsChild Neurology SocietyCan synophthalmia recur in the same family?
It can recur if there is an inheritable genetic cause; if no clear cause is found, recurrence risk may be lower but not zero. HPE ResearchIs surgery used to separate the eyes?
No. The eye field is fused because of deep developmental brain fusion. Cosmetic or functional separation is not feasible; surgery is only for related problems (like feeding or hydrocephalus). StatPearlsWhat support is available for families?
Counseling, palliative care teams, rare disease support groups, early intervention programs, and social services can all help. StatPearlsChild Neurology Foundation
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: August 01, 2025.
