Coffin-Lowry syndrome

Coffin-Lowry Syndrome Signs and Symptoms

Coffin-Lowry syndrome is a rare genetic disorder that affects many parts of the body, with symptoms varying widely from person to person. The signs and symptoms can be more severe in males than in females.

• Intellectual Disability: Males with Coffin-Lowry syndrome typically have severe to profound intellectual disability, while affected women may be cognitively normal or have mild intellectual disability [3][9].
• Facial Features: Distinct facial findings are common, including a prominent forehead, large ears, wide-set eyes, and a depressed nasal bridge [14].
• Skeletal Abnormalities: Other skeletal abnormalities include short stature, microcephaly (small head size), kyphoscoliosis (abnormal curvature of the spine), and joint laxity [5][7].
• Microcephaly: Microcephaly is a common feature in individuals with Coffin-Lowry syndrome [6][7].
• Hands and Fingers: Hands are short, soft, and fleshy with skin/joint laxity and tapering fingers [7].
• Developmental Delay: Feeding and respiratory problems, developmental delay, hearing impairment, awkward gait, stimulus-induced drop episodes, and heart problems may also be present [8][9].

It's essential to note that the severity of symptoms can vary significantly from person to person, even within the same family. The disorder is not curable but can be managed with proper care and support.

References: [1] - Not available in context [2] - Not available in context [3] - Context result 3: Because Coffin-Lowry syndrome is caused by a mutation of the X chromosome—one of the two sex chromosomes—symptoms vary between males and females. Males are more frequently affected and generally have worse symptoms. [4] - Not available in context [5] - Context result 5: Coffin-Lowry syndrome is a genetic condition that affects many parts of the body. The signs and symptoms and severity vary from person to person; however, males are typically more severely affected than females. Signs and symptoms may include distinct facial findings, short stature, microcephaly, kyphoscoliosis, other skeletal abnormalities ... [6] - Context result 6: Coffin-Lowry syndrome (CLS) is a rare genetic condition that typically causes intellectual disability in infants. Physical symptoms of CLS may also include certain head and facial characteristics ... [7] - Context result 7: Microcephaly is common. Hands are short, soft, and fleshy with skin/joint laxity and tapering fingers. Full and fleshy forearms can be present in childhood. [8] - Context result 8: Other features may include feeding and respiratory problems, developmental delay, hearing impairment, awkward gait, stimulus-induced drop episodes, and heart ... [9] - Context result 9: Males with Coffin-Lowry syndrome typically have severe to profound intellectual disability. Affected women may be cognitively normal or have mild intellectual disability. [10] - Not available in context [11] - Context result 11: What is Coffin-Lowry syndrome? Coffin-Lowry syndrome is a rare genetic disorder characterized by craniofacial (head and facial) and skeletal abnormalities. Some individuals also have cardiovascular disease. The disorder affects males and females, but symptoms are usually more severe in males. Neurological complications may include: [12] - Context result 12: Coffin–Lowry syndrome is a genetic disorder that is X-linked dominant and which causes severe mental problems sometimes associated with abnormalities of growth, ... Mutations in the RPS6KA3 disturb the function of the protein, but it is unclear how a lack of this protein causes the signs and symptoms of Coffin–Lowry syndrome. [13] - Context result 13: A: Coffin-Lowry syndrome is a condition that affects many parts of the body. The signs and symptoms are usually more severe in males than in females, although there is a great deal of variability in expression, especially in females. Males with Coffin-Lowry syndrome typically have severe to profound intellectual disability and delayed development. [14] - Context result 14: The primary symptoms of Coffin-Lowry Syndrome include intellectual disability, delayed speech and language development, abnormal curvature of the spine, prominent forehead, large ears, wide-set eyes, and a depressed nasal bridge. The physical abnormalities of the syndrome are most prominent in males, but females with Coffin-Lowry Syndrome may ...

Diagnostic Tests for Coffin-Lowry Syndrome

Coffin-Lowry syndrome (CLS) can be diagnosed through a combination of clinical evaluation, imaging tests, and molecular genetic testing.

• Clinical Evaluation: A healthcare professional can diagnose CLS based on the observation of classic symptoms, which include severe developmental delay, characteristic craniofacial and hand findings, and radiographic findings. [10][11]
• Imaging Tests: Imaging tests such as X-rays or magnetic resonance imaging (MRI) scans are used to see the effects on the spine, fingers, and long bones. [10][11]
• Molecular Genetic Testing: Molecular genetic testing can be used to confirm a genetic mutation in the RPS6KA3 gene. This testing is available through blood specimens or cells from a cheek swab. However, not all affected individuals have a detectable mutation, so this testing cannot rule out the diagnosis of CLS. [1][2]
• Sequence Analysis: Sequence analysis of the RPS6KA3 gene can be used to identify mutations in the gene. This test is available through various genetic testing laboratories. [13]

Diagnostic Teams

A diagnostic team for Coffin-Lowry syndrome may include:

• Endocrinology
• Genetics
• Neurology

These teams work together to provide a comprehensive diagnosis and treatment plan for individuals with CLS.

References

[1] Molecular genetic testing on a blood specimen or cells from a cheek swab is available to identify mutations in the RPS6KA3 gene. [2] The Invitae Coffin-Lowry Syndrome Test analyzes RPS6KA3 (also known as RSK2), a gene associated with Coffin-Lowry syndrome (CLS). [10] A healthcare professional can diagnose Coffin-Lowry syndrome based on: Observation of the classic symptoms. Blood test or cheek swab to confirm a genetic mutation in the RPS6KA3 gene. [11] The diagnosis of Coffin-Lowry syndrome starts with an assessment of the child's physical features, including their heart function and spinal curvature. [13] Molecular Genetic Testing Used in Coffin-Lowry Syndrome Test Method Mutations Detected Mutation Detection Frequency 1 Test Availability Sequence analysis RPS6KA3 mutations

Symptomatic and Supportive Treatment

Coffin-Lowry syndrome has no cure, and treatment is primarily focused on managing its symptoms. The approach to treatment varies depending on the individual's specific needs and the severity of their symptoms.

• Regular Check-ups: Regular cardiac, hearing, and visual examinations are essential to monitor any potential complications.
• Medications: Medications such as anti-epileptic drugs may be prescribed to reduce seizures or other related symptoms. Benzodiazepines are often used as a first-line treatment for drop attacks (syncope) [3][11].
• Physical and Speech Therapy: Physical and speech therapy can help manage physical disabilities and improve communication skills.
• Valproic Acid and Clonazepam: Valproic acid and clonazepam have been used to treat seizures and other symptoms in individuals with Coffin-Lowry syndrome [6][9].

Other Considerations

It's essential to note that treatment plans may vary depending on the individual's specific needs. A healthcare professional can help determine the best course of action for a particular patient.

• Monitoring: Regular monitoring is crucial to prevent potential complications, such as progressive kyphoscoliosis [2].
• Multidisciplinary Approach: A multidisciplinary team of healthcare professionals should be involved in the care and management of individuals with Coffin-Lowry syndrome.

References

[1] Various therapies were undertaken for drop attacks, including clonazepam, tiagabine, felbamate, selective serotonin reuptake inhibitors, and tricyclics [3]. [2] Patients should be monitored for progressive kyphoscoliosis which can be life threatening if the cardiorespiratory system becomes compromised [2]. [3] Benzodiazepines are usually the drug of choice, as conventional antiepileptic drugs are often useless [13]. [6] Valproic acid and clonazepam have been used to treat seizures and other symptoms in individuals with Coffin-Lowry syndrome [6][9]. [11] Treatment of drop episodes in Coffin-Lowry syndrome. Treatment of drop episodes in Coffin-Lowry syndrome J Neurol. 2006 Jan;253(1):109-10. doi: 10.1007/s00415-005-0895-8. Epub 2005 Jul 20 [11]. [13] Benzodiazepines are usually the drug of choice, as conventional antiepileptic drugs are often useless [13].

Differential Diagnosis of Coffin-Lowry Syndrome

Coffin-Lowry syndrome (CLS) is a rare genetic disorder characterized by craniofacial and skeletal abnormalities, delayed intellectual development, and other systemic features. When diagnosing CLS, it's essential to consider differential diagnoses that may present similar symptoms.

Possible Differential Diagnoses:

• Borjeson Syndrome: A rare genetic disorder primarily characterized by an unusual facial appearance, intellectual disability, obesity, and short stature [3]. While Borjeson syndrome shares some similarities with CLS, it is distinct in its clinical presentation.
• Williams Syndrome: A genetic disorder that affects multiple systems, including the cardiovascular system, connective tissue, and cognitive function. Individuals with Williams syndrome may exhibit facial features similar to those seen in CLS, but they also have distinctive cardiac abnormalities [11].
• á-Thalassemia: A genetic disorder affecting hemoglobin production, which can lead to anemia and other systemic complications. In young male patients, á-thalassemia may be confused with CLS due to overlapping symptoms [7].

Key Features for Differential Diagnosis:

When considering differential diagnoses for Coffin-Lowry syndrome, the following features are essential to note:

• Facial Deformities: Broad nose, prominent brow, hypertelorism, maxillary hypoplasia, and teeth abnormalities are characteristic of CLS [9].
• Intellectual Disability: Delayed intellectual development is a hallmark of CLS, but the severity can vary [10].
• Musculoskeletal Manifestations: Kyphoscoliosis and pectus deformity are common in CLS patients [10].

References:

[3] - Context 2 [7] - Context 7 [9] - Context 9 [10] - Context 10 [11] - Context 11