Fryns microphthalmia syndrome is a very rare genetic condition in which a baby is born with absent eyes (anophthalmia) or very small eyes (microphthalmia) plus other features of the face and body, especially cleft lip and/or cleft palate and sometimes deeper facial clefts. Many babies also have ear differences, widely spaced eyes, and other organ problems (for example, spine, brain, heart, kidneys). Doctors consider it part of the broader spectrum of conditions where the eyes do not form normally before birth. A number of reports suggest the pattern can run in families in an autosomal recessive way (both parents carry one silent copy), although the exact single “cause-gene” has not been firmly pinned down for this specific named syndrome. Clinicians therefore diagnose it mainly by the combination of eye findings and facial clefting with other anomalies, after they rule out similar syndromes. Orpha+2Monarch Initiative+2
Fryns microphthalmia syndrome describes babies born with a combination of features classically seen in Fryns syndrome—a rare, usually autosomal-recessive condition—with severe eye underdevelopment (microphthalmia) or absence of an eye (anophthalmia). The Fryns picture often includes a hole in the diaphragm before birth (congenital diaphragmatic hernia), under-developed lungs, distinctive facial features, short nails or fingertip bones, and differences in many organs. When the eye is very small or absent, vision is severely affected and the face and eye socket may grow differently; early eye-socket expansion and prosthetic planning help growth and appearance. Survival and long-term outcomes depend mainly on the lung and diaphragm problems and on other organ differences that may occur with the eye findings. PMC+3NCBI+3MedlinePlus+3
Scientists now recognize that several genes involved in early body and eye formation can lead to a Fryns-like picture, and biallelic variants in PIGN (a gene used to build GPI-anchors on cell surfaces) are a confirmed cause in some families once labeled Fryns syndrome. Eye malformations such as microphthalmia/anophthalmia are genetically diverse (dozens of genes like SOX2, OTX2, PAX6, CHD7 and others), and the same gene can cause different severities in the eye and body. That is why modern care includes genomic testing and careful genetic counseling for families. BioMed Central+3GIM Journal+3PMC+3
Fryns microphthalmia syndrome” is used as a synonym for Anophthalmia-plus syndrome in rare-disease catalogs. Separately, Fryns syndrome (without the word “microphthalmia”) is a different, broader condition best known for congenital diaphragmatic hernia but it can also include microphthalmia—this sometimes causes confusion in names. MedlinePlus+3Orpha+3Orpha+3
Other names
Anophthalmia-plus syndrome
Microphthalmia with facial clefting
Fryns microphthalmia syndrome (terminology used in Orphanet/MONDO)
Historical labels in reports may include Fryns anophthalmia syndrome or Leichtman-Wood-Rohn syndrome. Orpha+1
Types
Because formal genetic sub-types are not fixed yet, clinicians often describe clinical patterns rather than official “types”:
Eye-severity pattern:
Anophthalmia (eyes absent clinically)
Severe microphthalmia (very small eyes)
Microphthalmia with coloboma/glaucoma/cornea clouding (some reports) PubMed+1
Laterality: Bilateral (both eyes) vs unilateral (one eye), though bilateral is frequent in published cases. PubMed
Facial-cleft pattern:
Cleft lip with/without cleft palate
Cleft palate only
Wider facial clefts/frontonasal clefting in a minority; these overlap with ALX1-related frontonasal dysplasia phenotypes. Orpha+1
Systemic-involvement pattern:
Ocular-dominant (mainly eye + cleft)
Multisystem (eye/cleft + spine/brain/renal/endocrine or airway features) as summarized in rare-disease databases and case reports. MalaCards
Causes
Key idea: For Fryns microphthalmia (Anophthalmia-plus) syndrome, the most supported cause is genetic and likely autosomal recessive, but the exact gene is not yet established, and doctors often evaluate genes known to cause anophthalmia/microphthalmia with facial clefts. Below are causes and contributors doctors consider (some are general to the MAC spectrum—microphthalmia/anophthalmia/coloboma—used in workup and counseling):
Autosomal-recessive inheritance (undetermined gene in APS) – Several families suggest recessive transmission; the specific gene for APS is not yet defined. Wiley Online Library+1
ALX1 gene variants – Can cause severe microphthalmia with facial clefting/frontonasal dysplasia, overlapping the APS picture. PMC
SOX2 variants – A leading cause of anophthalmia/microphthalmia syndromes; included in differential panels. MedlinePlus+1
OTX2 variants – Transcription factor important for eye development; linked to MAC spectrum. MedlinePlus
PAX6 variants – Master eye-development gene; MAC spectrum. MedlinePlus
ALDH1A3 variants – Retinoic-acid pathway; a recognized MAC gene. MedlinePlus
STRA6/RBP4 pathway – Vitamin A transport/signaling; associated with eye malformations and sometimes facial anomalies. MedlinePlus
BCOR variants – Cause Lenz microphthalmia syndrome (X-linked), a key differential. NORD
CHD7 variants – CHARGE syndrome (includes coloboma/ear/choanal defects); in the differential. MedlinePlus
SMOC1 variants – Linked to microphthalmia with limb anomalies; part of MAC gene panels. Breda Genetics
FOXE3, BMP4, RAX/VSX2 (CHX10), SIX3/SIX6, HESX1 – Additional eye-patterning genes frequently screened. MedlinePlus
FREM1/FREM2/FRAS1 – Basement-membrane/craniofacial genes known in syndromic clefting with ocular anomalies. Breda Genetics
Chromosomal abnormalities – Copy-number changes can underlie MAC; microarray may detect these. ScienceDirect
Sporadic de novo variants – A new change in the child without parental history is common in MAC. MedlinePlus
Maternal vitamin A (retinoid) exposure – Excess (e.g., isotretinoin) or deficiency can disrupt eye formation. Cleveland Clinic
Maternal infections (e.g., rubella, CMV) – Recognized risks for severe eye malformations. Cleveland Clinic
Maternal diabetes – Associated with a higher risk of major malformations including eye anomalies. Cleveland Clinic
Alcohol and certain teratogens – Have been linked to ocular maldevelopment. Cleveland Clinic
Multifactorial mechanisms – Genes + environment acting together may explain many cases. Cleveland Clinic
Unknown/undetected genetic causes – Despite modern testing, a portion remains unexplained. MedlinePlus
Symptoms & signs
Absent or very small eyes → main feature; vision usually severely affected. NORD
Cleft lip and/or cleft palate → feeding and speech difficulties later; surgical repair is typical. Orpha
Wider facial clefts/frontonasal clefting in some babies; nose and central face may be split or very wide. PMC
Corneal clouding → the clear front window of the eye looks cloudy. PMC
Glaucoma → high pressure in the eye in some reports. PubMed
Coloboma → a “gap” in iris/retina/optic nerve in some eyes. PubMed
Hypertelorism → eyes set widely apart. MalaCards
Ear anomalies/low-set ears → shape or position differences. MalaCards
Choanal atresia/stenosis → blockage or narrowing behind the nose causing noisy breathing. MalaCards
Spinal/sacral defects → hemivertebrae, sacral agenesis, tethered cord in some cases. PubMed
Brain differences → under-developed corpus callosum or large ventricles (hydrocephalus/ventriculomegaly). MalaCards
Endocrine problems → reported in some babies. MalaCards
Feeding/breathing difficulties in newborn period due to clefts or airway anomalies. NORD
Developmental delay may occur, depending on brain/eye involvement and associated anomalies. gene.vision
General growth issues or multiple congenital anomalies across organs (kidneys/heart etc.) in subsets. MalaCards
Diagnostic tests
Physical examination
Newborn head-and-face exam – Doctor looks for eye size/shape, facial clefts, nose shape, ear position, and spacing of eyes to recognize the pattern. Orpha
Oral/palate check and feeding assessment – Identifies cleft palate or difficulty sucking to guide early feeding support. Orpha
Airway and nasal exam – Checks for choanal atresia/stenosis causing noisy or obstructed breathing. MalaCards
Whole-body anomaly screen – Looks for spine, limb, genital, heart, and kidney differences to document the full syndrome. MalaCards
Manual/clinical ophthalmic tests
External ocular exam & pupillary light response – Basic assessment of eye presence/size and light reaction. EyeWiki
Slit-lamp biomicroscopy (if possible) – Magnified view for corneal clouding, lens issues, and anterior segment structure. EyeWiki
Intraocular pressure (tonometry) – Screens for glaucoma when an eye is present. EyeWiki
Dilated fundus exam – Looks for coloboma/retinal changes (where visualization is feasible). EyeWiki
Socket/soft-tissue assessment – For anophthalmia or severe microphthalmia, to plan early socket expansion with conformers. EyeWiki
Laboratory & pathological/genetic tests
Chromosomal microarray (CMA) – Detects small deletions/duplications that can cause MAC phenotypes. ScienceDirect
Targeted multigene panel for anophthalmia/microphthalmia – Tests dozens of eye-development genes (e.g., SOX2, OTX2, PAX6, ALDH1A3, STRA6, BCOR, CHD7, etc.). MedlinePlus
Whole-exome or whole-genome sequencing – Used when panel is negative to search broadly for a causative variant. (Testing guides list APS under ORPHA:1104 for selection.) Eurofins Biomnis Connect
Parental studies & segregation – Clarify whether a variant is inherited (supports recessive/X-linked patterns) or new. MedlinePlus
Infectious disease labs (as indicated) – Congenital infections like CMV/rubella are checked if suspected. Cleveland Clinic
Metabolic or endocrine panels (as indicated) – When clinical signs suggest hormonal or metabolic involvement. MalaCards
Electrodiagnostic tests
Electroretinography (ERG) – Measures retinal function; often limited or absent in severe micro/anophthalmia but can document residual function. gene.vision
Visual evoked potentials (VEP) – Assesses the brain’s response to visual signals; helps when the eye exam is difficult. gene.vision
EEG (if seizures) – Some babies with brain malformations may need seizure evaluation. (General MAC care guidance.) gene.vision
Imaging tests
Prenatal ultrasound and fetal MRI – May detect small or absent globes, facial clefts, and associated anomalies before birth. Orpha
Postnatal orbital ultrasound (B-scan) – Helps define the size/structure of the eye socket and any remnant eye tissue. EyeWiki
MRI of brain and orbits – Looks at optic nerves, brain structures (e.g., corpus callosum), ventricles, and midline defects. MalaCards
CT of facial bones/orbits (selected cases) – Maps bony anatomy for surgical planning in clefts or prosthetic fitting. EyeWiki
System screening imaging – e.g., echocardiogram, renal ultrasound, and spine imaging as guided by the physical exam. MalaCards
Non-pharmacological treatments (therapies & others)
How to read this section: each item gives an elaborate description (≈150 words), purpose, and mechanism in simple language. These are supportive, family-centered options used alongside medical and surgical care.
Multidisciplinary care pathway (NICU + specialty center)
Description: Babies with Fryns features and eye malformations need a coordinated plan that links prenatal counseling, delivery, immediate breathing support, CDH management, and follow-up for feeding, growth, and development. Specialized centers use protocols for gentle ventilation, pulmonary hypertension monitoring, and timely surgery. A case manager helps coordinate neonatology, cardiology, pulmonology, surgery, ophthalmology/oculoplastics, genetics, rehab, nutrition, and social work. Family meetings review goals, procedures, and supports. Purpose: improve survival, reduce complications, and ensure families understand options. Mechanism: organized teamwork reduces delays, applies consistent evidence-based steps, and anticipates problems like reflux and oral aversion. BMJ Nutrition+1Prenatal planning and delivery optimization
Description: When CDH or severe anomalies are seen on ultrasound/MRI, families receive counseling about delivery at a tertiary center, possible fetal therapy (FETO) in select severe CDH cases, steroid timing, and neonatal resuscitation plans. Delivery room teams avoid bag-mask ventilation (which can worsen stomach inflation) and prepare for immediate intubation and gentle ventilation. Purpose: reduce lung injury at birth, optimize oxygen delivery, and line up early interventions. Mechanism: careful delivery protocols and, if applicable, FETO increase chances that hypoplastic lungs can adapt postnatally, while avoiding gastric insufflation and high airway pressures. Translational Pediatrics+1Gentle ventilation strategies
Description: After birth, gentle ventilation means using lower pressures, permissive carbon dioxide levels, and careful oxygen targets to protect fragile lungs. High-frequency ventilation may be used if conventional settings risk lung injury. Purpose: minimize ventilator-induced lung damage and support gas exchange while the baby stabilizes. Mechanism: lung-protective settings reduce over-distension and inflammation in hypoplastic lungs, improving short-term stability and readiness for surgery. UC Davis Health+1Pulmonary hypertension monitoring and protocols
Description: Many infants with CDH have high pressure in lung blood vessels (pulmonary hypertension). Teams use echocardiography, near-infrared spectroscopy, and standardized escalation steps. Purpose: promptly detect and treat pulmonary hypertension to maintain heart function and oxygen delivery. Mechanism: structured monitoring triggers timely support measures (e.g., ventilation adjustments, fluid balance, targeted medicines—see drug section). PMC+1Timed surgical repair of the diaphragm (CDH repair)
Description: Surgeons close the diaphragmatic defect after the infant is stabilized, sometimes with a patch for large defects. Purpose: restore separation of chest and abdomen, prevent abdominal organs from crowding the lungs/heart, and improve breathing mechanics. Mechanism: anatomical repair reduces lung compression and supports long-term respiratory function. BMJ NutritionFeeding therapy and nutrition support
Description: Children with CDH often have reflux, oral aversion, and high calorie needs. Feeding therapists, dietitians, and gastroenterology create step-wise plans using thickened feeds, positional strategies, specialized formulas, or breastfeeding support. Purpose: ensure growth, reduce reflux symptoms, and improve feeding skills. Mechanism: smaller frequent feeds, thickening, and tailored formulas reduce reflux and aspiration risk while meeting energy needs. ScienceDirect+1Reflux-focused behavioral and positional strategies
Description: Non-drug steps include upright holding after feeds, careful burping, smaller volumes, and avoiding tight diapers. Purpose: reduce discomfort, vomiting, and aspiration risk. Mechanism: gravity and slower gastric filling lower reflux pressure events; parent coaching builds consistency at home. AAFPEarly ocular-socket expansion with clear conformers
Description: For anophthalmia/microphthalmia, oculoplastic teams place small clear shells (“conformers”) that are gradually upsized to stimulate eyelid and socket growth; the clear design lets doctors monitor any tiny eye tissue. Purpose: promote symmetrical facial growth and prepare for a prosthetic eye. Mechanism: gentle mechanical expansion guides soft-tissue growth during infancy when tissues are most adaptable. NatureCustom ocular prosthesis and progressive expansion
Description: After sufficient socket growth, a custom ocular prosthesis is fitted; periodic enlargement maintains symmetry. Purpose: improve cosmesis, eyelid function, tear film distribution, and psychosocial wellbeing. Mechanism: prosthetic volume replaces the absent eye, supporting orbital bone and soft-tissue development. PMC+1Socket surgery if needed (conjunctival sac/palpebral fissure)
Description: When soft tissues are too tight, minor procedures enlarge the socket or eyelid opening to accept conformers/prosthesis. Purpose: enable proper prosthetic fit and comfort. Mechanism: surgical release increases space and reduces scarring, improving prosthetic retention. PMC+1Vision habilitation and developmental therapies
Description: Even with little or no vision, early orientation-and-mobility training, tactile exploration, and communication tools (including early intervention services) support development. Purpose: maximize functional independence and learning. Mechanism: neuroplasticity and adapted skills compensate for visual loss, improving milestones. BioMed CentralRespiratory physiotherapy and airway clearance
Description: Gentle airway clearance and positioning can help some infants with ongoing lung vulnerability after CDH repair. Purpose: reduce atelectasis and infections. Mechanism: targeted techniques optimize ventilation-perfusion and mucus clearance in hypoplastic lungs. BMJ NutritionCardiorespiratory monitoring at home (as indicated)
Description: Selected infants go home with simple monitors or oxygen plans. Purpose: detect desaturation events and support safe growth. Mechanism: continuous or spot checks prompt timely clinical review if instability occurs. BMJ NutritionFamily psychosocial support and counseling
Description: Social workers and psychologists address stress, grief, complex decision-making, and expectations. Purpose: sustain caregiver wellbeing and informed choices. Mechanism: structured counseling improves coping and adherence to care plans. BMJ NutritionGenetic counseling and cascade testing
Description: Families learn inheritance patterns (often autosomal recessive), recurrence risks, and options for future pregnancies. Purpose: empower planning and connect families to research when appropriate. Mechanism: explaining the role of genes (e.g., PIGN or eye-development genes) informs reproductive decisions. PMC+1Hearing screening and early audiology care
Description: Syndromic eye conditions can accompany ear differences; early screening catches hearing loss that would compound developmental delay. Purpose: protect speech and learning. Mechanism: prompt amplification or therapy reduces language delay. BioMed CentralDental and craniofacial follow-up
Description: Orofacial clefts or facial differences need coordinated dental/ENT/craniofacial review. Purpose: support feeding, speech, and facial growth. Mechanism: staged dental and surgical planning optimizes function and appearance. Wiley Online LibraryEarly intervention (physio/OT/speech)
Description: Structured therapies address hypotonia, fine motor, or oral-motor challenges. Purpose: improve motor skills, feeding, and communication. Mechanism: repetitive, goal-directed practice builds strength, coordination, and safe swallow. AAP PublicationsSchool vision services and assistive technology
Description: As children grow, low-vision services, tactile learning tools, and mobility training are arranged. Purpose: educational access and safety. Mechanism: accommodations and devices offset sensory limits to support learning. BioMed CentralTransition-to-adulthood planning (for survivors)
Description: Teens and families plan transfer to adult providers for lungs, heart, GI, and prosthetic care, plus vocational and psychosocial support. Purpose: preserve continuity of care and independence. Mechanism: structured handoff reduces health gaps and maintains prosthetic and reflux management. PMC
Drug treatments
Note: There is no disease-modifying drug for Fryns microphthalmia syndrome. Medicines are individualized by specialists for CDH-related lung disease, pulmonary hypertension, reflux, seizures, infections, pain, and nutrition. Doses are weight-based and protocol-driven in neonates/children; exact dosing must follow local guidelines. The list below explains common categories used in care; your team selects and titrates therapy. BMJ Nutrition+1
Inhaled nitric oxide (iNO) — Pulmonary vasodilator; NICU protocol dosing
Long description (≈150 words): iNO relaxes smooth muscle in lung blood vessels, lowering pressure and improving oxygenation in selected infants with pulmonary hypertension after CDH. It is delivered through the ventilator circuit and adjusted based on oxygenation, echocardiography, and potential methemoglobinemia risk. Class: selective pulmonary vasodilator gas. Dosage/Time: protocolized, continuous inhalation in NICU. Purpose: reduce right-to-left shunting and improve oxygen delivery. Mechanism: activates guanylate cyclase via nitric oxide, raising cGMP in pulmonary vasculature, causing vasodilation. Side effects: methemoglobinemia, rebound PH if abruptly stopped. NatureSildenafil — Phosphodiesterase-5 inhibitor
Helps manage persistent pulmonary hypertension by preventing cGMP breakdown, complementing or following iNO. Pediatric dosing is specialist-directed (oral/IV). Possible side effects: hypotension, flushing. NatureMilrinone — Phosphodiesterase-3 inhibitor/inodilator
Sometimes used when heart function and pulmonary pressures are both concerns; improves cardiac output and causes vasodilation. Side effects include arrhythmias and hypotension; dosing is ICU-titrated. NatureProstaglandin analogs (e.g., epoprostenol/iloprost—specialist use)
Used in selected pulmonary hypertension scenarios as vasodilators; routes and dosing are specialist-controlled due to potency. Side effects: hypotension, flushing, jaw pain (depending on agent). NatureGentle sedation/analgesia (e.g., morphine/fentanyl per protocol)
Used briefly to improve ventilator synchrony and reduce stress; dosing is cautious to avoid respiratory depression and withdrawal. BMJ NutritionDiuretics (e.g., furosemide)
For fluid management in lung disease or heart strain; reduces pulmonary edema risk. Watch electrolytes and kidney function. BMJ NutritionVasoactive support (e.g., norepinephrine/vasopressin—ICU use)
Supports blood pressure and organ perfusion if hypotension occurs during critical illness; titrated in ICU with continuous monitoring. BMJ NutritionSurfactant (case-by-case)
In some centers, exogenous surfactant may be considered if clinical indicators suggest surfactant deficiency; decisions are individualized. BMJ NutritionProton-pump inhibitors (PPIs)
For significant GERD documented in CDH survivors; aim to protect esophagus and reduce pain/vomiting with reflux. Side effects include altered microbiome and, with chronic use, possible nutrient effects—therapy is periodically reassessed. jpedsurg.orgH2-receptor blockers
An alternative or bridge for reflux control when PPIs are not preferred; dosing is pediatric-specific. Side effects may include tachyphylaxis. AAFPProkinetics (selected cases)
In difficult GERD/feeding cases, specialist may trial a prokinetic agent to improve gastric emptying; careful risk-benefit and monitoring are required. AAFPThickening agents/formula modifications (adjunct to meds)
Although not “drugs,” thickening strategies often accompany reflux regimens; listed here to emphasize combined approaches under supervision. AAFPAntiemetics (short-term)
Used sparingly for distressing vomiting while the underlying reflux and feeding plan is optimized. AAFPAntibiotics (treat infections only)
CDH survivors may be infection-prone; antibiotics target proven bacterial infections and should not be used for uncomplicated reflux. BMJ NutritionAnticonvulsants (e.g., levetiracetam)
Used if a child with Fryns features develops seizures from brain malformations or hypoxia; agent choice and dosing are individualized to EEG and age. NCBIBronchodilators (selected reactive airway cases)
Some survivors have reactive airway symptoms; bronchodilators are trialed based on response, not routinely. BMJ NutritionInhaled corticosteroids (selected cases)
For persistent airway inflammation with symptoms; specialist-guided, with growth and side-effect monitoring. BMJ NutritionNutritional pharmacotherapy (e.g., medium-chain triglyceride formulas—adjunct)
Special formulas may be used under dietitian direction to meet high caloric needs and reduce reflux burden. ScienceDirectPulmonary vasodilator transition regimens (outpatient)
Some children transition from NICU vasodilators to oral agents during follow-up; careful weaning prevents rebound PH. NatureVaccinations and RSV/viral prophylaxis as eligible
Immunizations and, when criteria are met, seasonal monoclonal antibody prophylaxis reduce respiratory infections that destabilize fragile lungs. BMJ Nutrition
Dietary molecular supplements
Note: Supplements do not treat the genetic cause but may support growth when guided by a clinician/dietitian. Always check interactions and suitability for infants/children.
Energy-dense formula modulars (e.g., MCT oil modular) — helps meet high energy needs without large volumes; mechanism: easier fat absorption and more calories per milliliter. ScienceDirect
Thickening starches or gums — reduce reflux by increasing feed viscosity; mechanism: slower gastric emptying and fewer regurgitation events. AAFP
Hydrolyzed or amino-acid formulas — for suspected cow-milk protein sensitivity worsening reflux/feeding; mechanism: reduced antigenicity and improved tolerance. AAFP
Vitamin D — supports bone health and general growth in children with limited outdoor activity or feeding challenges. AAP Publications
Iron (if deficient) — addresses iron deficiency from prematurity/illness; mechanism: restores hemoglobin and supports development. AAP Publications
Calcium/phosphate (if low) — supports bone mineralization with chronic illness or PPI use; monitored to avoid imbalance. AAP Publications
Omega-3 fatty acids (age-appropriate formulations) — may help overall nutrition; mechanism: essential fatty acids for growth and cell membranes. AAP Publications
Probiotics (selected cases) — sometimes considered for reflux/feeding programs; mechanism: microbiome modulation (evidence mixed; clinician-guided). AAFP
Electrolyte supplements (as indicated) — replace losses with diuretics or illness; mechanism: maintain cardiac/neuromuscular function. BMJ Nutrition
Micronutrient multivitamin (age-appropriate) — supports general needs when intake is borderline; mechanism: covers common gaps during complex feeding plans. AAP Publications
Drugs for immunity booster / regenerative / stem-cell
There are no proven immune-booster or regenerative/stem-cell drugs that correct Fryns microphthalmia syndrome. Care focuses on prevention of infection and protecting fragile lungs. Below are the practical, ethical “immunity-support” measures clinicians actually use in this setting. BMJ Nutrition
Routine vaccinations (per schedule) — dosage and timing per national program; function: prevent common infections that would worsen lung disease. Mechanism: active immunity via antigen exposure. BMJ Nutrition
Monoclonal antibody prophylaxis for RSV (seasonal, if eligible) — dosage per weight/season protocol; function: passive immunity to reduce RSV hospitalization in high-risk infants. Mechanism: neutralizes RSV F protein. BMJ Nutrition
Nutritional optimization (prescribed calories/protein, see diet section) — not a drug, but the most effective “immune support”; mechanism: adequate substrate for immune cells and healing. ScienceDirect
Pulmonary vasodilator stewardship (e.g., sildenafil) to maintain lung health — dosage protocolized; function: reduces PH episodes that predispose to decompensation during infections. Mechanism: pulmonary vascular cGMP pathway. Nature
Vitamin D supplementation (if deficient) — dosage per pediatric guidelines; function: supports immune modulation and bone health; mechanism: vitamin-D receptor signaling in immune cells. AAP Publications
No stem-cell therapy recommended — investigational stem-cell products are not standard for Fryns or AMC and should only be used within regulated trials; mechanism claims are unproven here. BioMed Central
Surgeries
Diaphragmatic hernia repair — Close the hole and return abdominal organs to abdomen; why: improve breathing mechanics and protect heart/lungs from compression. BMJ Nutrition
Eye-socket (conjunctival sac) expansion / eyelid surgery — Create room for conformers/prosthesis; why: promote symmetric facial/orbital growth and comfortable prosthetic wear. PMC
Gastrostomy tube (G-tube) placement (selected) — Provide reliable nutrition when oral feeding is unsafe/insufficient; why: support growth and reduce aspiration. ScienceDirect
Anti-reflux surgery (e.g., Nissen fundoplication in refractory cases) — Tighten the lower esophageal sphincter mechanism; why: control severe GERD causing pain, poor growth, or aspiration. jpedsurg.org
Cleft lip/palate repair (if present) — Reconstruct anatomy for feeding and speech; why: improve nutrition, reduce ear problems, and support language development. Wiley Online Library
Preventions
Deliver and treat in an experienced center to apply standardized, evidence-based CDH protocols. ScienceDirect
Prenatal counseling and planning to reduce delivery-room risks. Translational Pediatrics
Avoid bag-mask ventilation at birth in known/suspected CDH to limit gastric insufflation. CMAJ
Follow reflux-reducing feeding strategies early. AAFP
Keep vaccines up to date to prevent respiratory infections. BMJ Nutrition
Early prosthetic/conformer program to guide socket growth. Nature
Scheduled echo and PH follow-ups for timely treatment adjustments. Nature
Nutrition and growth monitoring with a dietitian. ScienceDirect
Early hearing/vision-related developmental support to protect milestones. BioMed Central
Family mental-health and social support to sustain long-term care consistency. BMJ Nutrition
When to see doctors
Seek medical help immediately if a child with Fryns features or CDH history has fast or difficult breathing, bluish skin, poor feeding, repeated vomiting with poor weight gain, fainting or unusual sleepiness, a new seizure, fever with breathing trouble, or if the prosthetic eye/socket becomes very painful, red, or dislodged. These signs can mean worsening lung hypertension, infection, dehydration, or socket complications that need urgent review. Routine visits should include pulmonology/cardiology (for PH), surgery (for CDH repair follow-up), gastroenterology/nutrition (for reflux/growth), ophthalmology/oculoplastics (for conformer/prosthesis changes), audiology, and developmental services. Nature+2jpedsurg.org+2
What to eat / what to avoid
Prefer small, frequent feeds and avoid overfilling the stomach. AAFP
Use thickened feeds when advised to cut regurgitation. AAFP
Consider hydrolyzed or amino-acid formulas if protein intolerance worsens reflux. AAFP
Hold upright after feeds; avoid lying flat immediately. AAFP
Work with a dietitian to reach calorie targets with acceptable volumes (e.g., modulars). ScienceDirect
Avoid large, spicy, very fatty meals (for older children) that can trigger reflux. AAFP
Limit carbonated drinks and late-evening meals (age-appropriate). AAFP
Support breastfeeding with lactation guidance when possible. PubMed
Ensure vitamins/minerals per pediatric guidance if intake is borderline. AAP Publications
Reassess diet as growth changes, because needs evolve quickly in infancy and early childhood. ScienceDirect
FAQs
1) Is Fryns microphthalmia syndrome genetic?
Usually yes. Classic Fryns is typically autosomal recessive; PIGN variants explain a Fryns-like picture in some families. Eye malformations (AM/Microphthalmia) involve many genes; testing helps clarify recurrence risk. NCBI+1
2) Can medicines cure Fryns syndrome or anophthalmia?
No. Treatments support breathing, feeding, growth, and socket development; there is no curative drug for the overall syndrome. NCBI
3) What determines survival?
Lung development and severity of the diaphragmatic defect are key; associated organ anomalies also matter. Care at experienced centers helps. BMJ Nutrition
4) What is FETO and who qualifies?
A fetal endoscopic balloon temporarily occludes the trachea in severe CDH to stimulate lung growth; used in very selected cases after specialist assessment. Translational Pediatrics
5) Why avoid bag-mask ventilation at birth?
It inflates the stomach/bowel, worsening chest compression in CDH; early intubation is preferred. CMAJ
6) How is pulmonary hypertension treated?
With careful ventilation and targeted vasodilators like iNO or sildenafil under strict protocols, plus echocardiography-guided adjustments. Nature
7) Why is feeding so hard?
GERD and oral aversion are common after CDH; energy needs are high and volumes must be balanced—hence dietitian-led plans and reflux care. jpedsurg.org
8) Can eye size be increased?
Yes—progressive conformers and custom prostheses expand the socket and support facial symmetry; sometimes minor socket surgery is needed. Nature+1
9) Will my child ever see from the affected eye?
With true anophthalmia there is no eye to see; with microphthalmia, vision varies based on internal structures. Early low-vision support maximizes function. BioMed Central
10) Do all families need genetic testing?
Testing is strongly advised to clarify cause, guide counseling, and connect to research or support groups. PMC
11) Are there stem-cell treatments for this?
No approved stem-cell therapy exists for Fryns or AMC; avoid unregulated offerings outside trials. BioMed Central
12) What is the long-term outlook?
Varies widely; some infants have critical lung disease, while others survive with ongoing feeding, reflux, and developmental needs requiring long-term follow-up. Genetic Diseases Center
13) Will my child need multiple surgeries?
Possibly—CDH repair is common; some need G-tube or anti-reflux surgery; some need socket/eyelid procedures and cleft repair if present. BMJ Nutrition+2jpedsurg.org+2
14) How often are eye prostheses adjusted?
Regularly during growth; the team enlarges or refits as the face changes to maintain symmetry and comfort. PMC
15) Where can I read more?
GeneReviews (Fryns), MedlinePlus, GARD/NORD summaries, and recent AMC management reviews are trustworthy starting points; clinicians can share center-specific protocols. NCBI+2MedlinePlus+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: September 19, 2025.
