Mitral Regurgitation-Hearing Loss-Skeletal Anomalies Syndrome

Mitral regurgitation-hearing loss-skeletal anomalies syndrome is best known as Cardiospondylocarpofacial (CSCF) syndrome and has been reported under the synonyms Forney syndrome / Forney-Robinson-Pascoe syndrome / Mitral regurgitation-deafness-skeletal anomalies syndrome. It is characterized by mitral valve disease (often regurgitation), hearing loss (often conductive), and multiple skeletal fusions/anomalies, with autosomal-dominant variants caused by MAP3K7 mutations. Because the condition is exceptionally rare, most day-to-day care follows evidence-based guidelines for its component problems (mitral regurgitation, hearing loss/otitis media, and orthopedic issues). Orpha.net+3AAO-HNS+3PubMed+3

Cardiospondylocarpofacial (CSCF) syndrome is a genetic condition that affects the heart valves (especially the mitral valve), the bones and joints (including spine, wrists/ankles), and hearing. People may have mitral regurgitation (the mitral valve leaks, so some blood flows backward in the heart), hearing loss (often due to middle-ear or inner-ear changes), short stature, and bone fusions in the spine and in the small bones of the wrist and ankle. Facial features and palate differences can also occur. Genetic studies have shown that some families have a change (mutation) in the MAP3K7 gene—which alters TGF-β signaling important for cartilage, bone, and heart development. Because only a small number of cases have been published, doctors treat the specific problems using standard heart, ear, and orthopedic care plans. AAO-HNS+2PubMed+2

Cardiospondylocarpofacial syndrome is a genetic condition that touches three main body systems at once: the heart, the ears, and the skeleton. The heart problem is usually mitral regurgitation (the mitral valve does not close tightly, so some blood leaks backward), sometimes linked to mitral valve prolapse. The hearing problem is often conductive hearing loss, which means sound cannot travel well through the outer/middle ear to the inner ear. The skeletal problems include short stature, short fingers, and fusions of small bones in the wrist (carpal) and ankle (tarsal) and sometimes neck (cervical) vertebrae, plus other bone differences. Because the same gene (MAP3K7) is active in many tissues, the features can vary from person to person, even within a family. The condition is autosomal dominant, so one changed copy of the gene is enough to cause it. Only a small number of families are reported worldwide, so doctors learn from each new case. MalaCards+4Orpha.net+4NCBI+4

Other names

This condition has appeared in the medical literature under several names. You may see: cardiospondylocarpofacial syndrome; Forney syndrome; Forney–Robinson–Pascoe syndrome; mitral regurgitation–deafness–skeletal anomalies syndrome; and mitral regurgitation–hearing loss–skeletal anomalies syndrome. All refer to the same rare disorder. Different names reflect the features that were noticed first in early family reports and later the broader picture clarified by genetic testing. Orpha.net+2MeSH Browser+2

Types

Doctors do not recognize formal “subtypes” of this syndrome. Instead, experts describe a spectrum of severity and emphasis—for example, some people have more cardiac involvement (mitral regurgitation or valve dysplasia), some have more skeletal fusions or short bones, and some have more ear differences and hearing loss. Recent case reports suggest certain MAP3K7 variant locations may be linked to more severe features, but data are still limited because so few patients exist. In short: one genetic cause, variable expression. PubMed+1

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Causes

Note: The primary cause is a pathogenic variant in MAP3K7. The items below describe mechanisms and contributors that explain why the features happen or what can worsen them; they are not separate diseases.

1. MAP3K7 gene variant (primary cause). Heterozygous (one-copy) variants in MAP3K7, which codes for TAK1, disrupt signaling that guides bone formation, inner-ear development, and heart valve structure. PubMed

2. Disrupted TGF-β signaling. TAK1 sits in pathways (including TGF-β) that regulate growth of cartilage, bone, heart valves, and ear structures; disturbance here can yield the triad of features. PubMed

3. Abnormal bone joint modeling. Carpal/tarsal and cervical vertebral fusions reflect errors in joint segmentation during fetal development influenced by MAP3K7 signaling. NCBI

4. Valve dysplasia. The mitral valve may be thick, elongated, or floppy (prolapse), leading to regurgitation because connective tissue maturation is altered. NCBI+1

5. Middle/inner ear malformations. Structural differences in ossicles or inner ear can impair sound conduction and sometimes sensorineural components. PubMed

6. Genetic dominance (haploinsufficiency or dominant-negative effects). One abnormal copy is enough; how the variant acts (loss-of-function or altered function) shapes severity. PubMed

7. Variant location within MAP3K7. Changes near key phosphorylation sites may drive more severe phenotypes (emerging genotype-phenotype links). Nature

8. Mosaicism in a parent. A parent with low-level mosaicism may be mildly affected but can pass a fully penetrant variant to a child. NCBI

9. Modifier genes. Other genes in connective-tissue and signaling pathways likely modify how strongly the features appear, explaining intrafamily variability. Wiley Online Library

10. Developmental timing. When and where signaling is most affected in the embryo determines which bones fuse or which valves are abnormal. PubMed

11. Mitral valve prolapse dynamics. Prolapse increases leaflet stress and can gradually worsen regurgitation over time. Mayo Clinic

12. Recurrent ear infections. Frequent otitis media (reported in some patients) can add conductive loss to structural hearing problems. Wikipedia

13. Joint hypermobility/soft tissue laxity. Some individuals show connective-tissue laxity that may contribute to valve prolapse and musculoskeletal symptoms. MalaCards

14. Growth retardation. Global growth signaling changes contribute to short stature and small hands/feet. NCBI

15. Carpal/tarsal synostosis. Fusion of wrist/ankle bones limits range of motion and reflects patterning errors. NCBI

16. Cervical vertebral synostosis. Fused neck vertebrae may change posture or cause stiffness/pain. NCBI

17. Autosomal-dominant inheritance across generations. Family clustering with vertical transmission is typical when a parent is affected. Orpha.net

18. Rare frequency. Extreme rarity means many doctors have limited experience, which can delay recognition and allow regurgitation or hearing problems to progress. Orpha.net

19. Overlap with connective-tissue disorders. Some cases show features that mimic other heritable connective-tissue diseases, complicating diagnosis and management pathways. Wiley Online Library

20. Potential association between prolapse and hearing loss (population data). Outside this syndrome, people with mitral valve prolapse have shown a higher risk of sudden sensorineural hearing loss; this does not cause CSCF, but it illustrates heart–ear connections relevant to care. PMC+1

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Symptoms

1. Mitral regurgitation (MR). The mitral valve leaks, so some blood flows backward into the left atrium during each beat. People may feel tired, short of breath on exertion, or hear a heart murmur; severity ranges from mild to severe. NCBI+1

2. Mitral valve prolapse (MVP). Valve leaflets billow into the atrium; some have chest discomfort or palpitations, but many are asymptomatic until the leak increases. Mayo Clinic

3. Conductive hearing loss. Sound does not pass efficiently through the middle ear, making speech seem muffled; children may need early hearing support to aid speech and learning. NCBI

4. Short stature and growth delay. Height below average for age is common; growth curves help track this over time. Orpha.net

5. Short fingers (brachydactyly) and small palms. Hands may look small, and fine motor tasks can be a bit harder, especially if joints are stiff. NCBI

6. Carpal/tarsal bone fusion. Fused wrist/ankle bones reduce flexibility and can cause discomfort with repetitive activity. NCBI

7. Cervical vertebral fusion. Limited neck movement or neck discomfort may occur; some have no symptoms and it is found on X-ray. NCBI

8. Facial features. Reported patterns include a long philtrum, up-slanting eye openings, anteverted nares, and posteriorly rotated ears; these are clues, not problems by themselves. MalaCards

9. High palate and dental issues. A high-arched palate and delayed or abnormal tooth eruption can affect bite and speech. Wikipedia

10. Joint hypermobility or laxity. Some joints move beyond the normal range; this can coexist with areas of bone fusion elsewhere. MalaCards

11. Scoliosis or other spinal differences. Curvature or segmentation anomalies may occur, requiring monitoring during growth. Wikipedia

12. Middle-ear infections. Recurrent otitis media can worsen hearing and may require ENT care or tympanostomy tubes. Wikipedia

13. Feeding difficulties in infancy. Some babies have trouble feeding and gaining weight; growth and nutrition support help. eScholarship

14. Kidney/urinary findings (less common). Horseshoe kidney or vesicoureteral reflux has been reported in some individuals. Wikipedia

15. Eye findings (less common). Strabismus or other ocular anomalies may occur in a subset of cases. Wikipedia

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Diagnostic tests

A) Physical examination

1. Comprehensive dysmorphology and growth exam. A genetics-informed physical exam looks for short stature, facial pattern, hand/foot size, joint range, spine alignment, and wrist/ankle flexibility. These bedside signs point to CSCF and guide further testing. NCBI+1

2. Cardiac auscultation. A clinician listens for a holosystolic murmur of MR or a mid-systolic click suggestive of MVP; exam results triage urgency for echocardiography. Mayo Clinic

3. Spine and neck mobility check. Reduced lateral rotation or extension can hint at cervical vertebral fusion; abnormal findings trigger imaging. NCBI

4. Hand/foot inspection. Short digits or limited wrist/ankle motion can suggest carpal/tarsal synostosis; simple bedside maneuvers can reveal stiffness. NCBI

5. ENT and oral exam. High palate, middle ear effusions, and tympanic membrane status guide hearing work-up and early treatment. Wikipedia

B) Manual/functional tests

6. Functional hearing screening. Age-appropriate bedside hearing screens (e.g., whispered voice, otoacoustic emissions in infants) quickly flag possible loss before formal audiology. NCBI

7. Joint range-of-motion testing. Goniometry documents restricted wrist/ankle movement from synostosis or generalized hypermobility elsewhere. NCBI

8. Posture and gait assessment. Observation for compensations due to fused segments or scoliosis helps target physical therapy and imaging. NCBI

9. Exercise tolerance assessment. Simple step or walk tests can uncover exertional breathlessness that suggests clinically important MR. Mayo Clinic

C) Laboratory & pathological tests

10. Genetic testing—targeted MAP3K7 sequencing. Confirms the diagnosis by finding a pathogenic variant; may be done as a single-gene test when suspicion is high. PubMed

11. Exome/genome sequencing. Helpful when the diagnosis is unclear; identifies MAP3K7 variants and can reveal mosaicism or other contributors. PubMed

12. Copy-number analysis. Detects rare deletions/duplications involving MAP3K7 if sequencing is negative but suspicion remains. NCBI

13. Variant interpretation with databases. Using resources (OMIM/MedGen/Orphanet) helps classify variants and counsel families about inheritance and risks. NCBI+1

14. Basic labs for surgical readiness. If valve repair or ENT procedures are planned, routine blood tests evaluate anesthesia/surgical safety; these do not diagnose CSCF but support care. Mayo Clinic

15. Family testing (cascade testing). Testing parents/siblings clarifies inheritance and recurrence risks; parental mosaicism can be uncovered. NCBI

D) Electrodiagnostic tests

16. Pure-tone audiometry with tympanometry. Measures hearing thresholds and middle-ear function; tympanometry detects conductive components such as ossicular or eardrum problems. NCBI

17. Auditory brainstem response (ABR). Objective measure for infants or when standard audiometry is not possible; helps separate conductive from sensorineural loss. NCBI

18. ECG and Holter (cardiac rhythm). Not specific to CSCF, but useful because valve disease and chamber enlargement can be associated with rhythm findings that affect management. NCBI

E) Imaging tests

19. Echocardiogram. The key test for MR/MVP; shows valve structure, amount of leakage, chamber sizes, and pumping function; repeated periodically to monitor change. Mayo Clinic

20. Cardiac MRI (selected cases). Adds 3-D detail on valves and chambers if echo images are limited or surgery is being planned. Mayo Clinic

21. Skeletal X-rays of wrist/ankle. Show carpal/tarsal fusions (synostoses) that explain stiffness and help confirm the skeletal pattern. NCBI

22. Cervical spine X-ray/CT. Reveals fused neck vertebrae and helps assess safety for procedures requiring neck positioning. NCBI

23. Temporal bone CT (selected). Defines middle-ear ossicles and other structures when surgery or device planning is considered. NCBI

Non-pharmacological (therapy/other) treatments

1. Regular cardiology follow-up with echocardiography – Periodic ultrasound checks of the heart track the size and function of the left ventricle and the severity of mitral regurgitation (MR). Early detection of LV enlargement or drop in ejection fraction guides the timing of valve repair or TEER, preventing irreversible heart damage. Mechanism: surveillance enables timely intervention per ACC/AHA thresholds. AHA Journals

2. Exercise prescription (aerobic, symptom-limited) – Structured, moderate aerobic activity improves functional capacity and quality of life in stable MR, while avoiding extreme isometric strain that spikes afterload. Mechanism: improved endothelial function, reduced neurohormonal activation, and better peripheral conditioning; training intensity is individualized per cardiology advice. AHA Journals

3. Sodium restriction and fluid management – When congestion occurs, limiting sodium (and sometimes fluids) can reduce edema and dyspnea, complementing diuretics if used. Mechanism: dietary sodium reduction lowers intravascular volume and venous pressures, decreasing pulmonary congestion. AHA Journals

4. Blood pressure optimization (lifestyle) – Weight control, DASH-style diet, and limiting alcohol help keep BP ideal for the LV in MR. Mechanism: lower systemic vascular resistance reduces regurgitant volume and LV wall stress. AHA Journals

5. Endocarditis prevention with oral hygiene – Excellent dental care and routine cleanings reduce bacteremia risk. Routine antibiotic prophylaxis is not recommended for most MR patients; it is reserved for the highest-risk structural conditions. Mechanism: minimizing transient bacteremia from poor oral health; antibiotics used only in guideline-defined high-risk hearts/procedures. www.heart.org+1

6. Hearing rehabilitation (hearing aids, assistive listening) – Audiology-guided fitting improves communication, school/work performance, and social functioning. Mechanism: amplification compensates for middle/inner-ear deficits; frequency-specific programming targets conductive or sensorineural loss patterns. AAO-HNS

7. Tympanostomy tube candidacy assessment – In children with recurrent/persistent otitis media with effusion and hearing impact, tubes can restore ventilation and improve hearing; decision follows AAO-HNS criteria. Mechanism: equalizes middle-ear pressure and drains effusion to reduce conductive loss. PubMed

8. Speech and language therapy (when indicated) – For children with hearing-related speech delay or palate anomalies, early intervention supports articulation and language development. Mechanism: targeted auditory-verbal training and articulation practice leverage neuroplasticity in early years. AAO-HNS

9. Physiotherapy and posture/core conditioning – Gentle range-of-motion, core strengthening, and posture training help pain and function with vertebral fusions/scoliosis, aiming to preserve mobility while protecting fused segments. Mechanism: improves paraspinal support and reduces mechanical strain. AAO-HNS

10. Orthotic support (custom insoles/wrist splints) – Supports compensate for tarsal/carpal fusion malalignment, improving gait and hand function. Mechanism: redistributes forces and stabilizes adjacent joints, lowering overuse pain. AAO-HNS

11. Bone health optimization – Adequate calcium/vitamin D intake, weight-bearing activity, and fall-prevention strategies; consider DEXA if growth delay or limited mobility. Mechanism: supports peak bone mass and reduces fracture risk in skeletal dysplasia. AAO-HNS

12. Educational accommodations – Preferential seating, captioning, FM systems, and individualized education plans facilitate learning for hearing impairment or musculoskeletal limitations. Mechanism: improves signal-to-noise ratio and reduces fatigue. AAO-HNS

13. Genetic counseling – Explains inheritance, recurrence risk, and family testing options (MAP3K7) with shared decision-making. Mechanism: informed reproductive planning and early surveillance of at-risk relatives. PubMed

14. Psychosocial support – Counseling and peer support help families manage a rare diagnosis, coordinate multi-specialty care, and reduce caregiver strain. Mechanism: improves adherence and quality of life. AAO-HNS

15. Activity/sports guidance – Tailored advice allows safe participation; avoid activities that trigger severe Valsalva or high cervical stress in those with fused vertebrae. Mechanism: matches cardiac reserve and skeletal limitations to activity demands. AHA Journals

16. Vaccinations (esp. influenza/pneumococcal per age/indication) – Reduces respiratory infections that can worsen heart failure or otitis media. Mechanism: lowers infection-related decompensation risk. AHA Journals

17. Weight and sleep optimization – Treating obesity and possible sleep-disordered breathing reduces BP and cardiac load; better sleep improves daytime function with hearing/orthopedic challenges. Mechanism: decreases sympathetic tone and afterload. AHA Journals

18. Pain management education – Non-opioid strategies (positioning, heat/ice, paced activity) for musculoskeletal pain from joint fusions or scoliosis; avoid NSAID overuse in those with renal risk. Mechanism: multimodal analgesia reduces disability. AAO-HNS

19. Care coordination (cardiology–ENT–orthopedics–genetics) – Regular multidisciplinary reviews align timing of ear procedures, cardiac interventions, and orthopedic surgeries. Mechanism: prevents conflicts (e.g., perioperative anticoagulation vs. ear surgery). AAO-HNS

20. Transition-to-adult-care planning – For adolescents, structured transfer to adult cardiology/ENT/orthopedics preserves continuity and surveillance. Mechanism: reduces loss-to-follow-up in a chronic rare disorder. AAO-HNS

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Drug treatments

(Evidence is extrapolated from guideline-driven care of MR and its complications; there is no drug that “cures” CSCF. Dosing must be individualized by a clinician. FDA labels cited; guideline context for when/why to use comes from ACC/AHA valvular guidance.) AHA Journals

1. Furosemide (loop diuretic) – Helps relieve breathlessness and edema when congestion from MR occurs. Typical oral starting doses vary; clinicians titrate to symptoms and kidney function. Purpose: fluid off-loading. Mechanism: inhibits NKCC2 in the loop of Henle to increase natriuresis/diuresis; watch electrolytes and renal function. Side effects: hypokalemia, dehydration, ototoxicity (rare). FDA Access Data+1

2. Torsemide (loop diuretic) – Alternative to furosemide with higher oral bioavailability and longer action; can help resistant edema. Mechanism/risks similar to furosemide; dose per clinician direction. FDA Access Data+1

3. Lisinopril (ACE inhibitor) – In MR with LV dysfunction or hypertension, afterload reduction may help symptoms and remodeling. Mechanism: blocks ACE to reduce angiotensin II; monitor potassium/creatinine and for cough/angioedema. FDA Access Data+1

4. Losartan or Valsartan (ARB) – ACE-intolerant patients may benefit from ARBs for afterload control and LV remodeling support. Mechanism: AT1 receptor blockade. (Representative FDA labels can be consulted for precise dosing and precautions.) AHA Journals

5. Sacubitril/valsartan (ARNI) – In selected patients with LV systolic dysfunction and heart-failure symptoms, ARNI improves outcomes compared with ACE/ARB alone; requires 36-hour ACE washout and careful BP/renal monitoring. Mechanism: neprilysin inhibition + RAAS blockade. FDA Access Data+1

6. Metoprolol succinate (β-blocker) – For patients who develop LV systolic dysfunction or arrhythmias, β-blockade improves survival in HFrEF and controls rate. Mechanism: β1 blockade lowers heart rate/contractility, allowing longer filling time. FDA Access Data+1

7. Spironolactone (MRA) – Add-on for LV systolic dysfunction with persistent symptoms to reduce mortality/hospitalization; watch potassium and renal function; risk of gynecomastia. Mechanism: aldosterone receptor antagonism. FDA Access Data

8. Eplerenone (MRA) – Alternative MRA with lower anti-androgen effects; similar monitoring needs. Mechanism: selective aldosterone blockade. (Consult FDA labeling for dosing/precautions.) AHA Journals

9. Dapagliflozin (SGLT2 inhibitor) – For heart-failure phenotypes (with or without diabetes) to reduce CV death and HF hospitalization; monitor volume status and genitourinary side effects. Mechanism: promotes glucosuria/natriuresis; cardio-renal benefits. FDA Access Data+1

10. Empagliflozin (SGLT2 inhibitor) – Similar HF benefits as dapagliflozin; check eGFR thresholds and ketoacidosis warnings even in non-diabetics. FDA Access Data+1

11. Hydralazine/Isosorbide dinitrate – In ACE/ARB/ARNI-intolerant patients or as add-on in selected HFrEF (particularly in certain populations), provides afterload and preload reduction. Mechanism: arterial (hydralazine) and venous (ISDN) vasodilation. (See FDA labels for both agents.) AHA Journals

12. Digoxin – Considered in persistent symptomatic HFrEF and/or rate control in atrial fibrillation; narrow therapeutic index—requires careful dosing. Mechanism: Na⁺/K⁺-ATPase inhibition increases inotropy and vagal tone. (See FDA labeling.) AHA Journals

13. Amiodarone – For clinically significant atrial/ventricular arrhythmias; used when other agents unsuitable. Mechanism: multi-channel antiarrhythmic; monitor thyroid, liver, lung. (See FDA labeling.) AHA Journals

14. Apixaban – If atrial fibrillation occurs with stroke risk, a DOAC is commonly chosen unless valve/prosthesis status dictates warfarin. Mechanism: factor Xa inhibition; dose by renal function/age/weight. (See FDA labeling.) AHA Journals

15. Warfarin – Anticoagulation when mechanical valve is placed or when DOACs are contraindicated; monitor INR and interactions. Mechanism: vitamin K antagonist. (FDA label.) AHA Journals

16. Acetaminophen (for pain/fever) – Safer first-line analgesic when musculoskeletal pain occurs; avoid NSAID overuse in CKD or HF. Mechanism: central COX inhibition (weak peripheral). (FDA label.) AHA Journals

17. Topical nasal steroids – If chronic eustachian tube dysfunction/allergic rhinitis contributes to middle-ear issues, topical therapy may help symptoms (per clinician judgment). Mechanism: local anti-inflammatory effects. (FDA labels vary by product.) PubMed

18. Antibiotics for acute otitis media (episode-based) – Short courses when bacterial AOM is diagnosed; choices follow local pediatric/adult guidelines. Note: Dental prophylaxis antibiotics are reserved only for high-risk cardiac conditions. Mechanism: eradication of bacterial pathogens. PubMed+1

19. Loop-thiazide sequential nephron blockade (specialist use) – For refractory edema, a clinician may combine a thiazide-type diuretic with a loop diuretic, with close electrolyte monitoring. Mechanism: blocks sodium reabsorption at multiple nephron sites. (FDA labels for individual agents.) AHA Journals

20. Potassium and magnesium repletion (as needed) – Corrects diuretic-induced losses to prevent arrhythmias and cramps; dosing individualized to labs. Mechanism: restores membrane stability and cardiac conduction. (FDA labels for specific salts.) AHA Journals

Important: The above medicines are examples clinicians may consider for the manifestations of CSCF. They are not disease-specific cures and must be prescribed and adjusted by a healthcare professional who knows the patient’s history.

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Dietary molecular supplements

(Supportive only; discuss with clinicians—evidence ranges from limited to moderate for symptom support or general health. Avoid interactions with heart medicines.)

1. Omega-3 fatty acids (EPA/DHA) – May modestly reduce triglycerides and support cardiovascular health; typical doses 1–2 g/day of combined EPA/DHA with meals; mechanism: anti-inflammatory, membrane effects. AHA Journals

2. Vitamin D – If low, repletion supports bone health; dosing per level (e.g., 800–2000 IU/day maintenance); mechanism: calcium homeostasis and bone mineralization. AAO-HNS

3. Calcium – Meet daily intake via diet/supplement only if deficient; mechanism: bone mineral substrate; avoid excess in kidney disease. AAO-HNS

4. Magnesium – Corrects deficiency that can worsen arrhythmia/muscle cramps; typical 200–400 mg/day as tolerated; mechanism: cofactor in cardiac conduction. AHA Journals

5. Coenzyme Q10 – Sometimes used for statin-associated myalgias/fatigue; limited cardiac data; ~100–200 mg/day; mechanism: mitochondrial electron transport. AHA Journals

6. L-carnitine – Experimental/adjunct in certain cardiomyopathy contexts; 1–3 g/day in divided doses; mechanism: fatty-acid transport into mitochondria. AHA Journals

7. Curcumin – Anti-inflammatory properties; variable bioavailability; ensure no interaction with anticoagulants. AHA Journals

8. Resveratrol – Antioxidant/AMPK effects; human cardiac outcome data limited. AHA Journals

9. Folate/B12 (if low) – Correcting deficiency lowers homocysteine and supports hematologic/neurologic health. AHA Journals

10. Potassium-rich foods – If not contraindicated, dietary potassium supports BP control; avoid supplements with MRAs/ARNI unless prescribed. AHA Journals

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Immunity-booster / regenerative / stem-cell drugs

There are no approved disease-modifying immune or stem-cell therapies for CSCF/MAP3K7-related disease. Any “regenerative” approaches remain experimental and should not be used outside clinical trials. Supportive items sometimes discussed:

1. Vaccines (influenza, pneumococcal as indicated) – Reduce infection burden that can destabilize heart/ear conditions; dosing per national schedules. Mechanism: adaptive immune priming. AHA Journals

2. Iron repletion (if deficient) – IV or oral iron to correct anemia that worsens cardiac symptoms; dosing per labs. Mechanism: restores oxygen delivery. AHA Journals

3. Vitamin D repletion (if deficient) – Supports innate and bone health; dosing per level. AAO-HNS

4. No approved stem-cell drug for MR – Surgical/TEER repair, not stem cells, addresses valve mechanics. AHA Journals

5. No approved gene therapy for MAP3K7 variants – Management remains supportive and surgical as needed. PubMed

6. Clinical-trial enrollment (if available) – Consider genetics-guided trials at tertiary centers for rare disorders. Mechanism: access to investigational options under oversight. AAO-HNS

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Surgeries / procedures

1. Mitral valve repair (surgical) – Reshapes or reinforces the native mitral valve to stop leakage. Indicated when MR is severe with symptoms or objective LV changes. Why: timely repair prevents heart failure and improves survival. AHA Journals

2. Mitral valve replacement (surgical) – Used when repair isn’t feasible. Mechanical valves require lifelong warfarin; bioprosthetic valves may need future re-intervention. Why: restores valve competence when repair is not possible. AHA Journals

3. Transcatheter edge-to-edge repair (TEER; e.g., MitraClip) – A catheter-based option for selected high-risk patients with primary MR who are not surgical candidates, improving symptoms and quality of life. Why: less invasive therapy aligned with guideline selection criteria. AHA Journals

4. Tympanostomy tube insertion – For recurrent/persistent otitis media with effusion impacting hearing/speech in children, following AAO-HNS criteria. Why: ventilates middle ear, improves conductive hearing. PubMed

5. Orthopedic surgery (targeted fusion release/stabilization, scoliosis procedures) – Selected cases with severe carpal/tarsal coalition or vertebral issues may need surgery to improve function or prevent neurologic compromise. Why: corrects alignment and preserves mobility. AAO-HNS

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Preventions (practical)

1. Keep dental hygiene excellent; routine cleanings; antibiotics only if high-risk cardiac criteria are met. www.heart.org

2. Vaccinate per schedule (flu, COVID-19, pneumococcal as indicated). AHA Journals

3. Control BP and avoid heavy isometric strain. AHA Journals

4. Healthy weight, smoke-free, limit alcohol. AHA Journals

5. Prompt treatment of ear infections to protect hearing. PubMed

6. Hearing protection from loud noise; safe earbud volumes. PubMed

7. Fall-prevention and safe activity plans for skeletal anomalies. AAO-HNS

8. Bone health: adequate calcium/vitamin D and weight-bearing exercise as advised. AAO-HNS

9. Regular follow-up with cardiology, ENT, orthopedics, and genetics. AAO-HNS

10. Family counseling/testing where indicated. PubMed

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When to see a doctor (red flags)

Seek medical care urgently for resting shortness of breath, chest pain, fainting, rapid weight gain/leg swelling, fever with a heart condition, new palpitations, sudden drop in hearing, severe ear pain/discharge, progressive limb weakness, or new neurologic symptoms. These can signal MR worsening, arrhythmia, infective endocarditis, acute otitis media/mastoiditis, or spinal cord compromise—conditions that require timely assessment. AHA Journals+1

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What to eat / what to avoid

1. Emphasize fruits, vegetables, whole grains, legumes, nuts, and fish (cardio-protective pattern). AHA Journals

2. Prefer low-sodium choices; read labels; aim for clinician-advised daily sodium goals. AHA Journals

3. Choose lean proteins; oily fish 1–2×/week for omega-3s. AHA Journals

4. Ensure adequate calcium/vitamin D intake for bone health (food first). AAO-HNS

5. Stay hydrated as advised (some with congestion need limits—follow clinician guidance). AHA Journals

6. Limit added sugars and ultra-processed foods to support weight and BP. AHA Journals

7. Avoid excess alcohol; abstain if advised for medications/arrhythmia. AHA Journals

8. Caution with herbal supplements that interact with anticoagulants/antiarrhythmics (e.g., St John’s wort). AHA Journals

9. Keep potassium intake diet-based; avoid OTC potassium if on MRAs/ARNI unless prescribed. AHA Journals

10. Maintain good oral health diet (limit sticky sugars; drink water after snacks) to support endocarditis prevention. www.heart.org

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Frequently asked questions

1) Is CSCF the same as Stickler syndrome?
No. Both can have hearing and skeletal issues, but CSCF prominently features mitral valve disease and bone fusions (carpal/tarsal, cervical) with reported MAP3K7 variants; Stickler is a collagenopathy (e.g., COL2A1/COL11A1) with major ocular risks. PubMed+2Wikipedia+2

2) How rare is CSCF?
Extremely rare—only a handful of families/cases reported worldwide; prevalence is far below 1 per million. AAO-HNS

3) What causes the heart leak (mitral regurgitation)?
Abnormal valve leaflets/chordae from connective-tissue development lead to poor valve coaptation, so blood leaks backward into the atrium during systole. PubMed

4) Can medicines fix the valve?
Medicines ease symptoms and protect the heart but do not repair a severely leaking mitral valve. Definitive treatments are surgical repair/replacement or TEER in selected patients. AHA Journals

5) When is surgery advised?
When MR is severe with symptoms, decreasing LV function, enlarging LV, or pulmonary hypertension—per guideline thresholds and heart-team assessment. AHA Journals

6) Are antibiotics needed before dental work?
Not routinely. They are recommended only for patients with the highest-risk cardiac conditions (e.g., certain prosthetic valves, prior endocarditis). Good oral hygiene is key for everyone. www.heart.org

7) What kind of hearing loss occurs?
Often conductive hearing loss from middle-ear issues; inner-ear abnormalities can also occur. Audiology testing guides management; tubes considered by guideline criteria. AAO-HNS

8) Will children outgrow the heart problem?
Mild MR can stay stable, but progressive or severe MR may require repair. Regular echocardiograms track changes over time. AHA Journals

9) Is genetic testing useful?
Yes—testing for MAP3K7 variants can confirm the diagnosis, inform family screening, and support tailored surveillance. PubMed

10) Can exercise make MR worse?
Appropriate moderate aerobic exercise is usually encouraged; avoid extreme isometric strain and follow cardiology guidance. AHA Journals

11) Are there special anesthesia concerns?
Anesthesiologists should know about MR severity, any anticoagulation, cervical vertebral fusions, and airway/palate features to plan safe intubation and hemodynamic management. AHA Journals

12) Are there clinical trials or registries?
Because CSCF is ultra-rare, families may explore rare-disease networks and academic centers for research opportunities and registries. AAO-HNS

13) Does CSCF affect lifespan?
Prognosis depends on mitral valve severity, timing of repair, and associated complications; with modern imaging and interventions, many outcomes improve. AHA Journals

14) Is pregnancy safe?
Pre-pregnancy counseling is essential. Severe MR can decompensate with increased blood volume; risk depends on baseline valve status and ventricular function. AHA Journals

15) How is CSCF different from OSMED?
OSMED is a collagen XI–related dysplasia with sensorineural hearing loss and skeletal changes, sometimes with valve prolapse, but it represents a distinct genetic entity and spectrum. NCBI+1

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Last Updated: November 11, 2025.

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