Forney Syndrome

Forney syndrome—better known to geneticists as Cardiospondylocarpofacial (CSCF) syndrome is an extremely rare, inherited condition that affects the heart, spine, wrists/ankles (carpal–tarsal bones), and the shape of the face and hands. Most people with this syndrome have short stature, fusion of some wrist and ankle bones, vertebral (spinal) fusion, conductive hearing loss, and heart valve problems, especially mitral valve regurgitation or prolapse. The condition is caused by single-gene (autosomal dominant) variants in MAP3K7, which codes for TAK1, a key switch in the TGF-β/BMP signaling pathways that guide bone, heart, and ear development. Because the underlying gene signal is disrupted, multiple organs form differently before birth. Only a small number of families have been reported worldwide. NCBI+2Wikipedia+2

Cardiospondylocarpofacial (CSCF) syndrome is an inherited condition that affects the heart (cardio-), spine (spondylo-), wrist/hand bones (carpo-), and face (-facial). People with CSCF may have mitral valve problems (like mitral regurgitation or prolapse), short stature, skeletal fusions in the wrists or spine, and conductive hearing loss. It is linked to single-copy (autosomal dominant) changes in the MAP3K7 gene, which encodes a signaling protein also called TAK1. Only a small number of families have been described worldwide, so information is limited and care is individualized by specialists. Wikipedia+1

The MAP3K7/TAK1 protein sits in a signaling pathway that cells use to respond to growth factors like TGF-β. When this pathway is disrupted by a pathogenic MAP3K7 variant, tissues that rely on tightly coordinated growth—cartilage, bone, and heart valves—can form differently. That’s why CSCF combines skeletal differences, valve disease, and sometimes facial features or hearing issues. Different MAP3K7 variants can lead to different problems—some cause CSCF, others cause frontometaphyseal dysplasia type 2—which is why doctors often order genetic testing to confirm the exact diagnosis. ScienceDirect+2Wiley Online Library+2

Another names

Doctors and databases may use several names for the same condition: Forney syndrome, Forney-Robinson-Pascoe syndrome, Mitral regurgitation–deafness–skeletal anomalies syndrome, and Cardiospondylocarpofacial (CSCF) syndrome. These names reflect the key problems (heart valve leak, hearing loss, skeletal/joint fusion, and facial/spinal features) and refer to the same MAP3K7-related disorder. Wikipedia+1

In Forney/CSCF syndrome, a pathogenic variant (usually loss-of-function) in MAP3K7 lowers or alters TAK1 activity. TAK1 normally relays TGF-β/BMP signals that tell developing tissues how to build bone, heart valves, and inner-ear structures. When TAK1 signaling is reduced, people can show carpal/tarsal and vertebral synostosis (bone fusion), cardiac valve dysplasia, and conductive hearing loss. The original genetic proof came in 2016 and has been expanded by later case reports. Wiley Online Library+3PubMed+3ScienceDirect+3

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Types

No official clinical subtypes exist.

Medical references do not recognize formal “types” of Forney/CSCF syndrome. Instead, clinicians describe one genetic disorder with variable expressivity (severity and features may differ person to person). Some papers informally group cases by which body systems are most affected (e.g., prominent cardiac valve disease, marked carpal/tarsal fusion, or severe vertebral involvement) or by MAP3K7 variant class (splice, truncating, missense at key domains), but these are descriptive—not standard types. NCBI+2Wiley Online Library+2

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Causes

The primary cause is a pathogenic variant in MAP3K7. Below are detailed, mechanism-level “causes” and contributors that explain how one gene change can create many findings.

1. MAP3K7 loss-of-function variants. Truncating or splice-disrupting variants reduce TAK1 protein, leading to weaker TGF-β/BMP signals during organ formation. PubMed+1

2. Missense variants in critical domains. Certain amino-acid changes in TAK1’s kinase or regulatory regions disturb signaling and reproduce the CSCF phenotype. Wiley Online Library

3. Aberrant splicing. Splice-site variants produce abnormal transcripts that lower functional TAK1, reported in multiple families. PMC

4. Haploinsufficiency. One healthy copy of MAP3K7 is not enough; reduced gene dosage leads to disease. PubMed

5. Disrupted TGF-β pathway. Downstream gene programs governing bone segmentation, valve cusp formation, and ear ossicle development are altered. PubMed

6. Disrupted BMP signaling. BMP cues for cartilage/bone patterning are partly TAK1-dependent; reduced throughput favors synostosis. PMC

7. Developmental timing effects. Early embryonic signaling windows are sensitive to TAK1; even modest reductions can shift final anatomy. PubMed

8. Dominant inheritance. A single pathogenic allele from an affected parent (or de novo) is sufficient. Wikipedia

9. De novo variants. Some children are first in the family with a new MAP3K7 variant arising in the egg, sperm, or embryo. PubMed

10. Mosaicism (possible). If only some cells carry the variant, features can be milder or patchy—recognized in many dominant syndromes and plausible here. Wiley Online Library

11. Genotype–phenotype differences vs FMD2. MAP3K7 gain-of-function variants cause frontometaphyseal dysplasia type 2 (FMD2), while loss-of-function variants cause CSCF; this explains overlapping but distinct skeletal findings. PMC+1

12. Valve tissue susceptibility. Valve leaflets rely on TGF-β cues; reduced TAK1 promotes mitral valve dysplasia and regurgitation. NCBI

13. Middle/inner ear development sensitivity. Ossicle and inner-ear malformations lead to conductive hearing loss. NCBI

14. Growth plate effects. Disturbed signaling in epiphyses contributes to short stature and brachydactyly. NCBI

15. Vertebral segmentation defects. Posterior cervical vertebral synostosis reflects failed separation of developing vertebrae. NCBI

16. Carpal–tarsal segmentation failure. Wrist/ankle bones fuse because partitioning signals are inadequate. NCBI

17. Joint laxity pathways. Altered extracellular-matrix regulation under TGF-β may cause laxity in some cases. malacards.org

18. Connective-tissue overlap. Some patients show features that resemble hereditary connective-tissue disorders, reflecting shared pathway biology. PMC

19. Variable expressivity and modifiers. Other genes and environment likely influence which organs are most affected. Wiley Online Library

20. Ultra-rarity and reporting bias. Few published families mean the spectrum we know is shaped by the most noticeable cases; the true range may be broader. Wiley Online Library

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Common symptoms and signs

1. Mitral valve regurgitation/prolapse. The mitral valve may not seal tightly, causing a backward leak that can be heard as a heart murmur and sometimes causes fatigue or shortness of breath. Wikipedia+1

2. Other cardiac defects. Some patients have septal defects or generalized valve dysplasia, detected by echocardiography. NCBI

3. Conductive hearing loss. Problems in the middle ear bones or inner-ear malformations reduce sound conduction; many children need early hearing evaluation. NCBI

4. Carpal–tarsal synostosis. Two or more small wrist/ankle bones fuse, limiting movement and sometimes changing gait or grip. NCBI

5. Vertebral fusion (often cervical). Fused neck vertebrae can limit neck motion and contribute to scoliosis or posture issues over time. NCBI

6. Brachydactyly and short palms/feet. Fingers and/or palms may be short due to bone patterning differences. Wikipedia

7. Short stature and growth delay. Height is typically below average; nutrition and endocrine assessments focus on overall health support. NCBI

8. Facial features. Common findings include hypertelorism (wide-set eyes), upslanting palpebral fissures, long philtrum, and posteriorly rotated ears; these features help pattern recognition but vary widely. malacards.org

9. High palate and dental anomalies. A high palate, delayed eruption, misalignment, or other dental issues can affect feeding and speech. Wikipedia

10. Joint hypermobility or laxity. Some joints move more than usual, likely due to connective-tissue signaling changes. malacards.org

11. Feeding difficulties and reflux. Infants may have trouble feeding and may develop gastroesophageal reflux, requiring supportive care. malacards.org

12. Genitourinary anomalies. Some reports describe vesicoureteral reflux or horseshoe kidney; screening is individualized. Wikipedia

13. Recurrent ear infections. Changes in ear anatomy can increase middle-ear infections, compounding hearing issues. Wikipedia

14. Scoliosis or rib synostosis. Spine and rib differences may gradually affect posture and comfort. Wikipedia

15. Ocular findings and strabismus (some cases). Eye alignment or structure differences are reported occasionally and should prompt ophthalmology review. Wikipedia

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Diagnostic tests

A) Physical examination

1. General dysmorphology and growth charting. A genetics-informed physical exam documents stature, facial pattern, hand/foot shapes, and joint range to build a clinical picture suggestive of CSCF. NCBI

2. Cardiac auscultation. Listening for a mitral regurgitation murmur guides urgent echocardiography referral. Wikipedia

3. Spine and neck mobility assessment. Limited cervical range of motion hints at vertebral fusion and steers imaging. NCBI

4. Gait and hand function assessment. Reduced wrist/ankle mobility from carpal–tarsal fusion can alter grip or gait, captured on exam to target therapy. NCBI

B) Manual/bedside tests

5. Tuning-fork tests (Rinne and Weber). Simple bedside checks separate conductive from sensorineural hearing loss; conductive patterns are common in CSCF. NCBI

6. Beighton score for joint hypermobility. A quick scoring of joint laxity supports connective-tissue involvement and therapy planning. malacards.org

7. Anthropometric measurements. Serial height/arm-span/segment measurements document growth delay and body-segment proportions. NCBI

8. Functional hand/wrist maneuvers. Grip tests and range-of-motion maneuvers detect carpal fusion limitations that may need occupational therapy. NCBI

C) Laboratory and pathological tests

9. Targeted genetic testing of MAP3K7. Sequencing confirms the diagnosis by finding a pathogenic MAP3K7 variant (often truncating or splice). PubMed

10. Clinical exome/genome sequencing. Broader panels are useful if the presentation overlaps other syndromes; they still identify MAP3K7 variants in CSCF. Wiley Online Library

11. Variant classification (ACMG/AMP). Laboratory assessment (segregation, de novo status, computational impact) supports pathogenicity of novel variants. Wiley Online Library

12. Copy-number analysis (exon-level CNV). If sequencing is negative, deletion/duplication testing can detect larger MAP3K7 changes. Wiley Online Library

13. Pathway-aware reanalysis over time. As new MAP3K7 cases are published, labs may re-interpret variants of uncertain significance. Wiley Online Library

D) Electrodiagnostic tests

14. Pure-tone audiometry. Audiology testing quantifies conductive hearing loss and monitors benefit from hearing aids or surgery. NCBI

15. Tympanometry. Middle-ear pressure and mobility testing clarifies the conductive component and helps track effusions. NCBI

16. Auditory brainstem response (ABR). Objective, electrophysiologic assessment of hearing pathways is useful in infants or difficult-to-test patients. NCBI

E) Imaging tests

17. Echocardiography. Ultrasound of the heart evaluates mitral valve structure and function, and screens for septal defects; it guides cardiology care. NCBI

18. Skeletal radiographs of hands/feet. X-rays identify carpal–tarsal fusion, brachydactyly, and other bone patterning differences. NCBI

19. Spine imaging (X-ray/MRI). Cervical and thoracic images show vertebral synostosis and scoliosis; MRI helps with soft-tissue and cord spacing. NCBI

20. Temporal-bone CT or targeted ear imaging. Selected cases benefit from imaging to define middle/inner-ear anatomy before surgical planning. NCBI

Non-pharmacological treatments (therapies & other care)

1. Multidisciplinary care plan. Coordinate cardiology, genetics, audiology, and orthopedics to track the heart, hearing, growth, and bones over time. This team approach is standard for complex, multi-system rare diseases. ScienceDirect

2. Regular echocardiograms. Periodic ultrasound checks of the mitral valve help decide if/when medication or procedures are needed, following valvular heart disease guidelines. AHA Journals+1

3. Activity pacing for valve symptoms. Shortness of breath or easy fatigue from mitral regurgitation improves with paced activity and rest while definitive treatment is planned. AHA Journals

4. Heart-healthy diet and salt awareness. Limiting excess salt can reduce fluid retention in people with valve-related heart failure symptoms; this is a standard supportive measure. AHA Journals

5. Audiology-led hearing rehabilitation. Early fitting of hearing aids (including OTC options in appropriate adults) can improve communication and quality of life; bone-anchored systems are options for conductive loss. U.S. Food and Drug Administration+2U.S. Food and Drug Administration+2

6. Speech-language therapy. Hearing loss and high palate can affect speech; therapy supports clearer articulation and language development. Wikipedia

7. Physical therapy. Tailored to posture, spinal mobility, and muscle balance, especially if scoliosis or vertebral anomalies are present. Wikipedia

8. Occupational therapy. Hand function training and adaptive tools help with carpal synostosis or brachydactyly in daily tasks. Wikipedia

9. Orthopedic bracing as indicated. Short-term bracing may support joints or spinal alignment while growth is monitored by specialists. Wikipedia

10. Educational supports. Hearing accommodations (preferential seating, FM systems) and individualized education plans can reduce classroom barriers. U.S. Food and Drug Administration

11. Regular dental care. Valve disease plus certain dental procedures can raise infection risks; good oral hygiene and guideline-based dental planning are encouraged (antibiotic prophylaxis is limited to specific high-risk groups). AHA Journals

12. Infection awareness. Prompt treatment of ear infections helps protect hearing in people prone to middle-ear problems. Wikipedia

13. Vision screening. Strabismus or other eye features, when present, benefit from early ophthalmology input. Wikipedia

14. Genetic counseling. Explains inheritance (often autosomal dominant) and options for family testing. Wikipedia

15. Psychosocial support. Coping with a rare diagnosis is hard; counseling and patient-family groups can help. Wikipedia

16. Weight and fitness guidance. Heart- and bone-friendly exercise improves stamina and mood; plans are individualized by cardiology/physiotherapy. AHA Journals

17. Fall-prevention strategies. If hand/foot anomalies affect balance or grip, home safety tweaks reduce injury risk. Wikipedia

18. Hearing-assistive tech. Remote mics and captioning tools complement hearing aids in noisy places. U.S. Food and Drug Administration

19. Bone-anchored hearing implants (when indicated). For select conductive losses, surgically implanted systems route sound through skull bone to the inner ear. FDA Access Data+1

20. Structured follow-up. Lifelong check-ins (especially for valves and hearing) catch changes early and guide timely interventions. AHA Journals

Drug treatments

Because CSCF itself has no disease-modifying drug, clinicians use standard, FDA-approved medications to manage mitral regurgitation symptoms or related conditions. Doses and timing are individualized—especially in children.

1. Enalapril (ACE inhibitor). Lowers afterload and helps symptoms in valve-related heart failure by blocking angiotensin-converting enzyme; typical oral dosing is individualized and titrated. Common effects: cough, kidney function changes, high potassium. FDA Access Data

2. Lisinopril (ACE inhibitor). Similar role to enalapril; clinicians choose based on patient factors and formulation. Side effects and precautions mirror the ACE-inhibitor class. AHA Journals

3. Captopril (ACE inhibitor). Shorter-acting option sometimes used in pediatrics where fine dose adjustments are needed. AHA Journals

4. Losartan (ARB). For ACE-intolerant patients; blocks angiotensin II receptor to reduce afterload and blood pressure; watch for dizziness, kidney effects, and high potassium. FDA Access Data+1

5. Valsartan (ARB). Alternative ARB with similar class effects and precautions. AHA Journals

6. Metoprolol tartrate/succinate (β-blocker). Slows heart rate and reduces oxygen demand; succinate is extended-release. Side effects can include fatigue and low heart rate; dosing is individualized. FDA Access Data+2FDA Access Data+2

7. Carvedilol (β-blocker with α-blockade). Used in heart-failure regimens when appropriate; titrate carefully under cardiology. AHA Journals

8. Furosemide (loop diuretic). Relieves fluid overload (leg swelling, breathlessness) by increasing urine output; dose and electrolytes must be monitored. FDA Access Data+1

9. Torsemide (loop diuretic). Longer half-life loop; chosen based on response and logistics. AHA Journals

10. Hydrochlorothiazide (thiazide). Sometimes added to loops for diuretic synergy; monitor sodium/potassium. FDA Access Data

11. Spironolactone (mineralocorticoid receptor antagonist). Potassium-sparing diuretic that counters aldosterone; monitor potassium and renal function. AHA Journals

12. Eplerenone (MRA). More selective alternative to spironolactone for patients with side effects. AHA Journals

13. Aspirin (antiplatelet) when indicated post-procedure. Sometimes used after certain valve procedures per surgeon/cardiologist protocols. AHA Journals

14. Warfarin (anticoagulant) for mechanical valves/AF. Required for mechanical prostheses or atrial fibrillation per guidelines; INR monitoring is essential. AHA Journals

15. Amoxicillin is not routinely used for dental prophylaxis unless a patient falls in a high-risk category defined by heart-valve guidelines (your cardiologist advises if you qualify). AHA Journals

16. Acetaminophen (analgesic). For musculoskeletal discomfort when NSAIDs aren’t preferred; follow label limits to protect the liver. AHA Journals

17. Ibuprofen/naproxen (NSAIDs). May ease orthopedic pain, but clinicians weigh GI/renal risks and valve/hemodynamic status. AHA Journals

18. Topical otic antibiotics (e.g., ofloxacin) for ear infections that can worsen conductive hearing loss—used only when infection is present. U.S. Food and Drug Administration

19. Decongestants are generally avoided for chronic use if they raise blood pressure/heart rate; discuss risks with your clinician. AHA Journals

20. Sedation/anesthesia medications are planned carefully before valve or orthopedic surgery per cardiology/anesthesia guidelines. AHA Journals

Why so many guideline citations? CSCF has no specific drug trials; care follows valvular heart disease and symptom-based standards. Individual product details above are supported by FDA labeling where cited.

Dietary molecular supplements

Always review supplements with your clinicians because of drug interactions and surgical plans.

1. Vitamin D to support bone health if low; mechanism: regulates calcium–phosphate balance and bone mineralization. Dose is individualized to blood levels. AHA Journals

2. Calcium for dietary gaps; mechanism: mineral substrate for bone; avoid excess if on certain diuretics. AHA Journals

3. Omega-3 fatty acids for general cardiometabolic support (dietary emphasis first). AHA Journals

4. Iron only if iron-deficiency anemia is documented; mechanism: hemoglobin synthesis. AHA Journals

5. Folate/B12 if lab-confirmed deficiency contributes to anemia or neuropathy. AHA Journals

6. Magnesium replacement when diuretics cause low levels; mechanism: cofactor in muscle/nerve function. FDA Access Data

7. Zinc short course if deficiency impairs wound healing after surgery. AHA Journals

8. Protein-adequate diet (or shakes if needed) to support growth, muscle, and post-op healing. AHA Journals

9. Iodine-adequate diet to support thyroid function (affects growth/energy); supplement only if deficient. AHA Journals

10. Multivitamin (age-appropriate) as a safety net when appetite is limited; avoid mega-doses. AHA Journals

Immunity/regenerative/stem-cell

There are no approved immune “boosters” or stem-cell drugs for CSCF. Care focuses on preventing infection and optimizing nutrition and recovery. Researchers continue to describe new MAP3K7 variants and phenotypes, but no gene-targeted therapy exists yet. Nature+1

Surgeries

1. Mitral valve repair or replacement. Indicated for severe, symptomatic mitral regurgitation or specific structural problems. Goals are to relieve symptoms and prevent heart enlargement/failure; approaches range from surgical repair to transcatheter edge-to-edge repair in select cases. AHA Journals+1

2. Bone-anchored hearing implant (BAHA/BONEBRIDGE). For appropriate conductive hearing loss, a titanium implant behind the ear transmits sound vibrations to the inner ear, bypassing the middle ear. FDA Access Data

3. Strabismus surgery. Realigns eye muscles to improve eye positioning when conservative measures fail. Wikipedia

4. Orthopedic correction (e.g., carpal synostosis release or spinal fusion for scoliosis). Done to improve function or prevent progression after specialist assessment. Wikipedia

5. Ear procedures (e.g., tympanostomy tubes). To reduce recurrent middle-ear infections that worsen conductive hearing loss. Wikipedia

Practical prevention tips

1. Keep heart and hearing follow-ups on schedule. AHA Journals

2. Maintain good dental hygiene and inform your dentist about valve disease. AHA Journals

3. Vaccinations (per national schedule) reduce respiratory/ear infections that can worsen hearing. Wikipedia

4. Treat ear infections promptly. Wikipedia

5. Use hearing protection in loud environments. U.S. Food and Drug Administration

6. Salt awareness if you have valve-related fluid symptoms. AHA Journals

7. Avoid smoking exposure—it harms ears, heart, and surgical healing. AHA Journals

8. Safe exercise plan cleared by cardiology. AHA Journals

9. Home safety tweaks to reduce falls if balance/hand issues exist. Wikipedia

10. Carry a medical summary (diagnosis, meds, devices, surgeries) for emergencies. AHA Journals

When to see a doctor urgently

Go now (ER or urgent clinic) for chest pain, severe breathlessness, fainting, fast/irregular heartbeat, sudden leg swelling, fever with a new heart murmur, rapidly worsening ear pain with discharge, or sudden hearing drop. These may signal valve deterioration, arrhythmia, infection, or acute ear disease that needs prompt care. AHA Journals

What to eat and what to limit

Emphasize: fruits/vegetables, whole grains, legumes, lean proteins, fish, and adequate calcium/vitamin D sources for bones; hydrate well. Limit: excessive salt (if you retain fluid), ultra-processed foods, large doses of caffeine if it worsens palpitations, and alcohol (if on anticoagulants or with heart symptoms). Always tailor to your cardiologist’s advice and any surgical plans. AHA Journals

FAQs

1) Is CSCF the same as Forney syndrome?
Yes—“Forney (Robinson–Pascoe) syndrome” is an older synonym; CSCF is the preferred name. Wikipedia

2) How is it diagnosed?
By recognizing the pattern of features and confirming a MAP3K7 variant on genetic testing. Wikipedia

3) How common is it?
Extremely rare; only a small number of families have been reported worldwide. Wikipedia

4) Is there a cure or a specific drug?
No. Treatment targets heart valve disease, hearing, and bones using standard therapies. ScienceDirect

5) Can hearing improve?
Yes—hearing aids or bone-anchored systems can greatly help conductive loss; results vary by person. U.S. Food and Drug Administration+1

6) Will everyone need heart surgery?
No. Some people are monitored for years; others may need mitral valve repair/replacement if leakage becomes severe or symptomatic. AHA Journals

7) Are over-the-counter hearing aids an option?
For adults with mild-to-moderate perceived hearing loss, yes—OTC hearing aids are FDA-regulated; children still need specialist-fitted devices. U.S. Food and Drug Administration

8) What about sports?
Most people can be active with cardiology guidance. Intensity depends on valve severity and symptoms. AHA Journals

9) Should family members be tested?
Because CSCF is often autosomal dominant, genetics teams often discuss cascade testing. Wikipedia

10) Do I need antibiotics before dental work?
Only if you meet specific high-risk criteria in valve guidelines—your cardiologist will advise. AHA Journals

11) Are pregnancy or anesthesia special issues?
Mitral regurgitation and airway/anatomic features may require tailored plans; involve cardiology/anesthesia early. AHA Journals

12) Could CSCF be confused with other MAP3K7 disorders?
Yes; frontometaphyseal dysplasia type 2 shares the gene but usually has a different, often gain-of-function variant and different features. Wiley Online Library

13) Are stem-cell treatments available?
No approved stem-cell or gene therapies exist for CSCF at this time. Nature

14) What’s the long-term outlook?
Highly variable; regular follow-up lets teams step in early if valves or hearing change. AHA Journals

15) Where can clinicians read more about MAP3K7 and CSCF?
Start with the 2016 AJHG paper and later variant reports that expand the phenotype. PubMed+1

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: November 11, 2025.