Frank-Ter Haar syndrome
frank-ter-har sin-drohm
Also known as: FTHS, Ter Haar syndrome
At a Glance
What is Frank-Ter Haar syndrome?
Frank-Ter Haar syndrome is a rare genetic disorder that primarily affects the skeletal system, eyes, and cardiovascular system. It is caused by mutations in the SH3PXD2B gene, which is important for normal development. Children with this condition often have distinctive facial features, such as a prominent forehead and widely spaced eyes. As they grow, they may experience developmental delays and issues with their heart and vision. Early symptoms can include poor feeding and growth, while later symptoms might involve joint abnormalities and vision problems. Early diagnosis is crucial to manage symptoms and improve quality of life. Families may face challenges due to the need for ongoing medical care and support. The prognosis varies, but with appropriate interventions, some individuals can lead relatively normal lives. Daily life for affected individuals often involves regular medical check-ups and therapies to address developmental and physical challenges. Supportive care from a multidisciplinary team can help manage the symptoms effectively. Genetic counseling is recommended for families to understand the inheritance pattern and risks for future pregnancies.
Medical Definition
Frank-Ter Haar syndrome is a genetic disorder characterized by craniofacial dysmorphism, skeletal anomalies, and cardiovascular defects. It is caused by mutations in the SH3PXD2B gene, which plays a role in cellular signaling and development. Histological findings may include abnormal bone and cartilage development. The syndrome is classified under rare genetic disorders with an autosomal recessive inheritance pattern. Epidemiologically, it is extremely rare, with only a few cases reported worldwide. The disease course can vary, but it often involves progressive skeletal and cardiovascular complications requiring medical intervention.
Frank-Ter Haar syndrome Symptoms
Symptoms vary in severity between individuals. Early diagnosis and management can significantly improve outcomes.
Very Common
Craniofacial dysmorphism in Frank-Ter Haar syndrome typically presents as a prominent forehead, widely spaced eyes, and a flat nasal bridge. This is caused by abnormal development of cranial and facial bones due to genetic mutations affecting bone growth. Over time, these features may become more pronounced as the child grows. It can affect the patient's self-esteem and social interactions, but surgical interventions and supportive therapies can help manage these challenges.
Skeletal abnormalities often manifest as joint laxity, short stature, and abnormal curvature of the spine. These issues arise from defects in connective tissue and bone formation, linked to mutations in the SH3PXD2B gene. As the patient ages, these skeletal issues can lead to mobility challenges and chronic pain. Physical therapy and orthopedic interventions can improve mobility and quality of life.
Cardiovascular defects, such as ventricular septal defects, are common in Frank-Ter Haar syndrome. These defects result from improper formation of the heart's septal walls during fetal development. If left untreated, they can lead to heart failure or other complications as the patient grows. Regular cardiac monitoring and surgical correction can mitigate these risks and improve patient outcomes.
Common
Ocular abnormalities may include glaucoma, retinal detachment, and other vision issues. These arise due to malformations in the eye's structure, often linked to connective tissue defects. Vision problems can worsen over time, potentially leading to blindness if not addressed. Regular ophthalmologic evaluations and timely surgical interventions are crucial for preserving vision.
Developmental delay is frequently observed, affecting motor skills, speech, and cognitive development. This delay is often a result of neurological involvement and structural brain anomalies. As the child grows, these delays can impact educational attainment and social integration. Early intervention programs, including speech and occupational therapy, can support developmental progress.
Hearing loss in Frank-Ter Haar syndrome can range from mild to severe and is often due to structural abnormalities in the ear. This symptom is caused by malformations in the ossicles or cochlea, affecting sound transmission. Over time, untreated hearing loss can lead to communication difficulties and social isolation. Hearing aids and other assistive devices can significantly improve auditory function and quality of life.
Less Common
Multiple facial angiofibromas may appear as small, benign tumors on the face. These are caused by overgrowth of fibrous tissue and blood vessels, potentially linked to genetic mutations affecting skin and connective tissue. While they may not pose a significant health risk, they can become more numerous and prominent with age. Dermatological treatments, including laser therapy, can help manage their appearance.
Hydrocephalus, or fluid accumulation in the brain, can occur due to impaired cerebrospinal fluid drainage. This condition results from structural brain anomalies associated with the syndrome. If untreated, it can lead to increased intracranial pressure, headaches, and neurological deficits. Surgical interventions, such as shunt placement, are often necessary to manage this condition and prevent complications.
What Causes Frank-Ter Haar syndrome?
Frank-Ter Haar syndrome is primarily caused by mutations in the SH3PXD2B gene, located on chromosome 5q35.1. The SH3PXD2B gene encodes a protein involved in cytoskeletal organization and cellular signaling pathways. Mutations in SH3PXD2B can lead to a malformed protein that fails to properly interact with other cytoskeletal components. This disruption causes defects in cellular structure and signaling, leading to impaired cell migration and adhesion. Dysfunctional cytoskeletal dynamics affect organelles such as the Golgi apparatus and endosomes, disrupting intracellular transport. These cellular dysfunctions extend to neighboring cells, causing tissue disorganization and developmental anomalies. Neuroinflammation may be triggered as a secondary response to cellular stress and damage. This inflammatory response can exacerbate degeneration of white matter and other neural structures. The specific pattern of symptoms, including craniofacial, skeletal, and cardiovascular anomalies, arises from the widespread impact of cytoskeletal dysfunction during development. Variability in disease severity among patients is likely due to differences in mutation types and their effects on protein function. Some mutations may allow partial protein function, leading to milder phenotypes, while others result in complete loss of function. Additionally, genetic background and environmental factors may influence the clinical presentation. The interplay between disrupted cellular pathways and compensatory mechanisms also contributes to phenotypic variability. Overall, the complex pathophysiology of Frank-Ter Haar syndrome reflects the critical role of SH3PXD2B in cellular and developmental processes.
How is Frank-Ter Haar syndrome Diagnosed?
Typical age of diagnosis: Frank-Ter Haar syndrome is typically diagnosed in infancy or early childhood when characteristic physical features and developmental delays become apparent.
The clinician looks for distinctive craniofacial features such as a prominent forehead, hypertelorism, and a depressed nasal bridge. A detailed family history is important to identify any hereditary patterns. Physical examination findings may include skeletal abnormalities like brachydactyly and joint laxity. This step helps narrow down the differential diagnosis to conditions with similar phenotypic presentations.
Radiographic imaging such as X-rays or CT scans is used to identify skeletal anomalies like vertebral segmentation defects and craniosynostosis. These specific abnormalities help confirm the diagnosis of Frank-Ter Haar syndrome. Imaging findings also assist in excluding other syndromes with overlapping features, such as Marfan syndrome. The presence of characteristic bone and joint abnormalities supports the clinical suspicion of the syndrome.
Routine laboratory tests may include metabolic panels to rule out other conditions. Specific biomarkers are not typically sought in Frank-Ter Haar syndrome. Abnormal results in these tests may guide further genetic testing. The absence of metabolic abnormalities helps focus on genetic causes.
Genetic testing involves sequencing the SH3PXD2B gene, where mutations are known to cause Frank-Ter Haar syndrome. Mutations such as missense or nonsense types are commonly identified. Positive results confirm the diagnosis and provide a basis for genetic counseling. These results are crucial for informing family members about recurrence risks and potential prenatal testing.
Frank-Ter Haar syndrome Treatment Options
NSAIDs are used to manage pain associated with joint abnormalities. They work by inhibiting cyclooxygenase enzymes, reducing inflammation and pain. Commonly used drugs include ibuprofen and naproxen. Clinical evidence supports their efficacy in providing symptomatic relief, although they do not address the underlying genetic cause. Side effects may include gastrointestinal upset and renal impairment with long-term use.
Techniques focus on improving fine motor skills and enhancing daily living activities. The therapeutic goals include increasing joint mobility and muscle strength. Sessions are typically conducted 2-3 times a week for several months. Measurable outcomes include improved functional independence and quality of life. Long-term benefits include better adaptation to physical limitations and enhanced developmental progress.
Surgery is indicated for craniosynostosis to prevent intracranial pressure increase. The procedure involves reshaping the skull to allow for normal brain growth. Expected benefits include improved cranial aesthetics and prevention of neurological complications. Surgical risks include infection and bleeding, necessitating careful monitoring. Post-operative care involves regular follow-up to assess skull growth and neurological status.
The care team typically includes geneticists, orthopedic surgeons, ophthalmologists, and physical therapists. Interventions focus on addressing specific symptoms and improving overall quality of life. Psychosocial support strategies are implemented to assist families in coping with the diagnosis. Family education is provided on the condition's progression and management strategies. A long-term monitoring plan is established to track developmental milestones and emerging complications.
When to See a Doctor for Frank-Ter Haar syndrome
- Severe breathing difficulties — this can indicate a life-threatening respiratory issue requiring immediate medical intervention.
- Sudden loss of vision — this could be a sign of retinal detachment, which needs urgent treatment to prevent permanent vision loss.
- Uncontrolled seizures — these can lead to serious complications and require emergency medical attention.
- Progressive vision changes — could indicate worsening eye conditions and should be evaluated by an ophthalmologist.
- Delayed developmental milestones — may suggest the need for early intervention services and specialist evaluation.
- Frequent headaches — could be a sign of increased intracranial pressure and should be assessed by a healthcare provider.
- Mild joint pain — monitor for any worsening or changes in mobility and consult a doctor if it persists.
- Occasional mild headaches — keep track of frequency and triggers, and discuss with a doctor if they become more frequent.
Frank-Ter Haar syndrome — Frequently Asked Questions
Is this condition hereditary?
Frank-Ter Haar syndrome is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. Parents of an individual with this condition are typically carriers but do not show symptoms. There is a 25% chance with each pregnancy for carrier parents to have an affected child. De novo mutations are rare but possible. Genetic counseling is recommended for families to understand their risks and options.
What is the life expectancy for someone with this condition?
Life expectancy can vary significantly based on the severity of symptoms and the presence of complications. Early onset of severe symptoms may correlate with a poorer prognosis. Mortality is often related to cardiovascular or respiratory complications. Early and ongoing treatment can improve quality of life and potentially extend lifespan. Families should discuss realistic expectations with their healthcare providers.
How is this condition diagnosed and how long does diagnosis take?
Diagnosis typically involves a combination of clinical evaluation, imaging studies, and genetic testing. The time from first symptoms to diagnosis can vary, often taking months to years due to the rarity of the condition. Specialists involved may include geneticists, ophthalmologists, and cardiologists. Delays in diagnosis are common due to symptom overlap with other conditions. Genetic testing confirming mutations in the SH3PXD2B gene is definitive for diagnosis.
Are there any new treatments or clinical trials available?
Research is ongoing, with some promising studies focusing on gene therapy and targeted molecular treatments. Novel approaches aim to address the underlying genetic causes of the syndrome. Clinical trials can be found on ClinicalTrials.gov by searching for Frank-Ter Haar syndrome or related terms. Patients should discuss potential participation in trials with their healthcare providers. New treatments may still be several years away from clinical use.
How does this condition affect daily life and activities?
Frank-Ter Haar syndrome can significantly impact mobility and self-care due to skeletal abnormalities. Educational support may be necessary due to developmental delays. Social and emotional challenges are common, requiring psychological support. The condition can place a considerable burden on families, necessitating external support and resources. Adaptive equipment and therapies can greatly enhance quality of life and independence.
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References
Content generated with support from peer-reviewed literature via PubMed.
- 1.Frank-ter Haar syndrome--additional findings?
Köse TE, İşler C, Şenel ŞN et al. · Dentomaxillofac Radiol · 2016 · PMID: 26582053
- 2.A severe case of Frank-ter Haar syndrome and literature review: Further delineation of the phenotypical spectrum.
Durand B, Stoetzel C, Schaefer E et al. · Eur J Med Genet · 2020 · PMID: 31978614
- 3.Further delineation of Frank-ter Haar syndrome.
Maas SM, Kayserili H, Lam J et al. · Am J Med Genet A · 2004 · PMID: 15523657
- 4.Frank-Ter Haar syndrome in a newborn.
Femitha P, Joy R, Gane BD et al. · Indian J Pediatr · 2012 · PMID: 22037860
- 5.Human Genetics of Ventricular Septal Defect.
Perrot A, Rickert-Sperling S · Adv Exp Med Biol · 2024 · PMID: 38884729
- 6.Multiple facial angiofibromas: A manifestation of Frank-ter Haar syndrome?
Borroni RG, Piscazzi F, Valenti M et al. · Am J Med Genet A · 2023 · PMID: 37141407
- 7.Retinal detachment in a child with Frank-ter Haar syndrome.
Furundaoturan O, Esen Baris M, Ayyıldız Emecen D et al. · Ophthalmic Genet · 2023 · PMID: 36004685
- 8.Identification of two novel SH3PXD2B gene mutations in Frank-Ter Haar syndrome by exome sequencing: Case report and review of the literature.
Zrhidri A, Jaouad IC, Lyahyai J et al. · Gene · 2017 · PMID: 28694206
This content is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment.Last reviewed: 2026-05-07