C syndrome, also known as Opitz trigonocephaly syndrome (OTCS) is a rare combination of several congenital anomalies and intellectual disabilities. It is characterized by trigonocephaly and metopic suture synostosis, dysmorphic facial features, a short neck, skeletal anomalies, and various intellectual disabilities.1
Due to its low occurrence, it frequently remains under-recognised within both the medical community and the public. This rarity poses a considerable challenge in terms of compiling extensive data, doing in-depth research and creating focused solutions. The shortage of cases also contributes to the lack of knowledge regarding C syndrome, making it challenging to provide prompt diagnosis and the proper care for those affected and their families. It becomes clear as we explore the nuances of C syndrome that understanding its complexities is essential for increasing medical knowledge and developing a more educated and inclusive society.2
On many levels, it is crucial to comprehend C syndrome. Understanding the complexities of this uncommon genetic illness from a medical perspective can result in earlier diagnoses, faster interventions, and customized treatment plans. In addition, by highlighting the difficulties faced by people with C syndrome and their families, we may encourage empathy and build a welcoming community that respects the variety of medical problems. Raising awareness of C syndrome not only helps people who are afflicted directly have better lives, but it also demonstrates the compassionate and inclusive nature of medical research and societal advancement.1
Causes of C syndrome
C syndrome is a heterogeneous disorder, which implies that it does not have a single underlying cause.2 Although many cases are sporadic, a mutation in the genetic material (in the CD96 gene) is the root cause of C syndrome.3
Signs and symptoms of C syndrome
C syndrome is characterised by a collection of symptoms that influence many aspects of a person’s well-being. Individuals who are impacted often have cognitive and developmental issues, such as learning problems, developmental delays, and intellectual disabilities. In addition, people with C syndrome may have physical abnormalities, such as distinctive facial features or other distinguishable physical characteristics. These may be accompanied by behavioural and neurological traits that have an impact on social relationships, communication skills and sensory processing.1
The wide spectrum of symptom severity seen among individuals with C syndrome is one noticeable feature of the condition. The complexity of diagnosis and treatment is further compounded by the wide spectrum of symptoms, from minor to severe. Some people may have relatively weaker symptoms of the illness, allowing them to function more independently on the daily. On the other hand, more serious instances can present significant obstacles that call for all-encompassing support and intervention techniques. In order to create effective treatment regimens and promote understanding among the medical community and society at large, it is crucial to recognize and accommodate this variability.4
This disease’s symptoms may first manifest when you are pregnant or with a newborn baby. The age at which symptoms may first develop varies depending on the condition. A single age range may or may not see the first signs of symptoms.2
The diagnosis of C syndrome might be challenging due to a number of issues. Healthcare providers must have a thorough understanding of the disorder because symptoms that are shared by other conditions might cause diagnostic uncertainty. It becomes crucial to distinguish C syndrome from related disorders in order to ensure proper diagnosis. Additionally, because the syndrome has genetic roots, specialised diagnostic techniques, such as DNA sequencing, are required to identify the precise mutations that cause the illness.4
Considering the complexity of C syndrome, multidisciplinary approaches to diagnoses are advised, such as obtaining clinical assessment and genetic testing. Collaboration amongst a variety of medical experts, including geneticists, neurologists, paediatricians, and developmental experts, is required for this. Every professional brings their own skills to diagnostic procedures, ensuring a comprehensive evaluation of the patient’s condition. This method improves diagnostic accuracy and enables a thorough grasp of the patient’s needs, assisting in the creation of individualized treatment regimens.5
Management and treatment options for C syndrome
Unfortunately, there is no cure for this syndrome. The treatment often focuses on the symptoms that are already present, together with supportive care. They include:5
- Therapy: The best outcomes for individuals with C syndrome can be achieved by early intervention. While occupational and physical therapy can address motor impairments and help patients attain greater independence in daily tasks, speech and language therapy can help people improve their communication abilities.
- Addressing cognitive and behavioural challenges: To reach their full potential, individuals with C syndrome need individualized educational support and specialised programs. The quality of their lives can be improved overall by using behavioural therapies to manage issues with social relationships, communication, and sensory processing.
- Medical treatment for specific symptoms: Seizures are one of the health problems that individuals with C syndrome may suffer. Effective seizure management, frequently incorporating medication, is essential to reducing their negative effects on a person’s well-being. In addition, medications to relieve pain can improve the patient’s general comfort.
- Psychosocial support: Suffering from C syndrome can physically and mentally affect patients and their families. Providing psychosocial assistance, knowledge, and resources can help them cope with the challenges and uncertainties brought on by the condition.
How common is C syndrome?
C syndrome is an extremely rare condition. The global medical literature has only documented roughly 60 people with C syndrome.3
Who is most at risk of C syndrome?
C syndrome appears to affect males and females equally. The prevalence of individuals affected with C syndrome is between 1 in 800,000 and 1 in 1,000,000.
How is C syndrome diagnosed?
Since C syndrome is still under-recognised, the reviewed clinical criteria for diagnoses include patients with severe mental retardation who have trigonocephaly and dysmorphic faces due to cerebral defects. 6 The process of diagnosis itself requires a thorough medical history, physical examination, and lab tests since the condition is still relatively uncommon.
What is the average life expectancy for individuals diagnosed with C disease?
Nearly 50% of individuals with C syndromes die during the first year of their life. However, some patients may have a normal quality of life,, such as having a normal IQ and living into early adulthood.7
Can we develop C syndrome later in life?
Conditions associated with C syndrome or Opitz syndrome are usually developed before or soon after birth (congenital).8
Are there any treatment options available for C syndrome?
As for now, there is no specific treatment for C syndrome. The main goals of treatments are symptom management and enhancing the patient’s quality of life. This involves medical care for specific symptoms like seizures, psychosocial support for patients and their families, and treatments to address developmental problems.5
How does C syndrome affect intellectual and developmental abilities?
Cognitive and developmental disorders, such as learning difficulties, developmental delays, and intellectual disabilities, are frequent in individuals with C syndrome. To ensure that these people achieve their full potential, early treatments like speech and language therapy and individualized educational support are essential.
When should I consult a medical professional?
If you suspect that someone you know might have C syndrome or any condition with similar symptoms, it is important to seek medical attention and consult a doctor. Some situations in which you should consider seeing a doctor includes:4
- Physical symptoms: Triangular head shape (trigonocephaly), dysmorphic facial features, or other distinctive physical characteristics that seem unusual or concerning
- Developmental delays: If you notice any developmental delays in a child’s milestones, such as speech, motor skills, or cognitive abilities, that are not progressing as expected
- Intellectual disabilities: Difficulties in learning, understanding, problem-solving, or intellectual functioning that seem unusual or significant in
- Concerns during pregnancy: If you are pregnant and receive information from prenatal testing or ultrasound that suggests possible developmental or genetic concerns
- Seizures or Neurological symptoms: If there are seizures, weird behaviours, and neurological symptoms that require further evaluations
C syndrome, a rare genetic condition known as Opitz trigonocephaly syndrome (OTCS), is characterised by a mix of prenatal abnormalities, intellectual incapacity, and unusual physical traits. Trigonocephaly, a dysmorphic facial characteristic, a short neck, skeletal abnormalities, and varied degrees of cerebral incapacity are some of the symptoms that it exhibits. Due to its rarity, C syndrome is frequently misdiagnosed, making diagnoses and treatment difficult. The condition, which has symptoms ranging from moderate to severe, is caused by mutations in the CD96 gene. The diagnosis is complicated and necessitates a multidisciplinary strategy that includes clinical evaluation and genetic testing. Despite the fact that there is no cure, management focuses on symptom reduction, with therapy to address developmental and cognitive difficulties, medical treatments for particular symptoms like seizures, and psychosocial support for patients and families. C syndrome is incredibly uncommon, involving only 60 known cases, and has a wide range of life expectancies from infancy to early maturity.
- RESERVED IU -- AR. Orphanet: C syndrome [Internet]. www.orpha.net. [cited 2023 Aug 17]. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1308#:~:text=C%20syndrome%20is%20a%20rare
- C syndrome - About the Disease - Genetic and Rare Diseases Information Center [Internet]. rarediseases.info.nih.gov. [cited 2023 Aug 17]. Available from: https://rarediseases.info.nih.gov/diseases/5978/c-syndrome
- C Syndrome - Symptoms, Causes, Treatment | NORD [Internet]. rarediseases.org. Available from: https://rarediseases.org/rare-diseases/c-syndrome/
- Urreizti R, Grinberg D, Balcells S. C syndrome - what do we know and what could the future hold? Expert Opinion on Orphan Drugs. 2019 Mar 4;7(3):91–4.
- Fierro JAA, Avina DAH. Opitz C syndrome: Trigonocephaly, mental retardation and craniofacial dysmorphism. Egyptian Journal of Medical Human Genetics. 2016 Jan;17(1):125–9.
- Travan, L., Pecile, V., Fertz, M., Fabretto, A., Brovedani, P., Demarini, S., & Opitz, J. M. (2011). Opitz trigonocephaly syndrome presenting with sudden unexplained death in the operating room: A case report. Journal of Medical Case Reports, 5, 222. https://doi.org/10.1186/1752-1947-5-222
- Smith Lemli Opitz Syndrome - NORD (National Organization for Rare Disorders) [Internet]. NORD (National Organization for Rare Disorders). NORD; 2015. Available from: https://rarediseases.org/rare-diseases/smith-lemli-opitz-syndrome/
- Kaname, T., Yanagi, K., Chinen, Y., Makita, Y., Okamoto, N., Maehara, H., Owan, I., Kanaya, F., Kubota, Y., Oike, Y., Yamamoto, T., Kurosawa, K., Fukushima, Y., Bohring, A., Opitz, J. M., Yoshiura, K., Niikawa, N., & Naritomi, K. (2007). Mutations in CD96, a member of the immunoglobulin superfamily, cause a form of the C (Opitz trigonocephaly) syndrome. American journal of human genetics, 81(4), 835–841. https://doi.org/10.1086/522014