40 Facts About Ogden Syndrome

What is Ogden Syndrome?

Ogden Syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic disorder. It presents a wide range of symptoms, primarily affecting males. Here are some key facts to understand this condition better.

1. Name Origin: Named after the hometown of the first family identified with the condition, Ogden Syndrome honors their hometown.

2. Genetic Cause: Caused by mutations in the NAA10 gene, specifically a recurrent missense variant Ser37Pro.

3. X-linked Disorder: Inherited in an X-linked recessive pattern, meaning it primarily affects males. Females can be carriers but typically do not exhibit severe symptoms unless they inherit two mutated copies of the gene.

Symptoms and Clinical Features

Ogden Syndrome manifests through various clinical features, making it a complex condition to manage.

4. Severe Phenotypes: Characterized by severe global developmental delays, craniofacial anomalies, hypotonia, cardiac arrhythmias, and eventually cardiomyopathy, leading to mortality during infancy in males.

5. Facial Features: Common facial features include large spaces between the bones of the skull, wrinkled forehead, prominent eyes, hypertelorism (widely spaced eyes), thick eyebrows, long eyelashes, relatively large ears, flared or prominent nostrils, upturned nose, protruding upper lip, small jaw or micrognathia, narrow palate, and small hands and feet.

6. Cardiac Issues: Individuals often have heart abnormalities, including prolonged QT intervals that cause irregular heart rhythms or congenital heart defects like atrial septal defects and ventricular septal defects.

7. Respiratory Problems: Reports of respiratory issues such as respiratory distress in infancy, pneumonia, frequent respiratory infections, apnea, pulmonary hypertension, and bronchiolitis.

8. Gastrointestinal Symptoms: Most individuals experience feeding difficulties during infancy. Other gastrointestinal problems include difficulty swallowing (dysphagia), aspiration issues, gastroesophageal reflux disease (GERD), vomiting, constipation, and diarrhea. Some may require a feeding tube.

9. Genitourinary Anomalies: Over half of affected males have genitourinary malformations, including inguinal hernia, small testes, and undescended testes (cryptorchidism). Less frequently, there have been reports of cystic renal dysplasia that can block urine flow and scar tissue in the kidneys (glomerulosclerosis).

10. Growth Delays: Affected individuals may be short for their height, have low weight, and have smaller head circumference in the first year of life.

Variability and Inheritance Patterns

The presentation of Ogden Syndrome can vary widely, even among individuals with the same genetic mutation.

11. Variable Phenotype: The condition presents with a wide spectrum of symptoms and severity. Females with one disease-causing variant in the NAA10 gene can vary from having no symptoms to having the same features as an affected male.

12. X-linked Dominant Pattern: While primarily X-linked recessive, there is evidence suggesting that some females can exhibit symptoms due to X-linked dominant inheritance patterns.

13. Rare Condition: Ogden syndrome is very rare, with around 20 cases reported in medical literature.

Developmental and Physical Characteristics

Understanding the developmental and physical characteristics can help in early diagnosis and management.

14. Developmental Delay: The primary symptom is severe global developmental delay, which affects various aspects of development.

15. Hypotonia: Affected individuals often exhibit hypotonia, which is characterized by low muscle tone.

16. Premature Aging Appearance: Patients typically present with a prematurely aged appearance due to reduced subcutaneous adipose tissue and redundant skin.

17. Skeletal Anomalies: Skeletal anomalies such as scoliosis and broad great toes are common.

18. Cardiac Arrhythmias: Cardiac arrhythmias are a significant feature, often leading to structural cardiac anomalies and early lethality.

Biochemical and Genetic Insights

Research into the biochemical and genetic aspects of Ogden Syndrome provides deeper insights into its mechanisms.

19. N-terminal Acetyltransferase Deficiency: The condition is also known as N-terminal acetyltransferase deficiency due to the role of the NAA10 gene in this process.

20. NatA Complex Formation: The S37P mutant in hNaa10 displays reduced catalytic activity and a reduced ability to form a NatA complex when co-expressed with hNaa15 in yeast.

21. Frameshift Mutations in hNAA15: De novo putative frameshift mutations in hNAA15 have been associated with congenital heart defects, consistent with minor cardiac anomalies seen in Ogden syndrome.

22. Truncated Naa10 Protein: An hNAA10 mutation resulting in a truncated Naa10 protein was found in a single family with Lenz microphthalmia syndrome, showing very little overlap with the Ogden syndrome phenotype.

23. Missense Mutations in hNAA10: De novo missense mutations in hNAA10 have been identified and suggested to be involved in two unrelated individuals with global developmental delays.

24. Hemizygous Hypomorphic Mutation: The hemizygous hypomorphic mutation in male infants with Ogden syndrome leads to decreased Nt-acetylation of key substrates important for physiological processes dysregulated in Ogden syndrome.

25. Impaired NatA-S37P Complex Formation: Impaired NatA-S37P complex formation and catalytic capacity of human proteins lead to reduced in vivo Nt-acetylation of a subset of proteins in cells from an Ogden syndrome family.

26. Altered Proliferation, Growth, and Migration: Ogden syndrome fibroblasts display altered proliferation, growth, and migration patterns due to the impaired Nt-acetylation.

Diagnosis and Management

Diagnosing and managing Ogden Syndrome involves a combination of genetic testing and symptomatic treatment.

27. Symptomatic Treatment: There is no cure or specific treatment for Ogden syndrome. All treatment is symptomatic, focusing on managing the various clinical features.

28. Diagnostic Confirmation: The only way to confirm a diagnosis is through whole exome sequencing, which identifies the pathogenic variants in the NAA10 gene.

Research and Resources

Ongoing research and available resources provide valuable information for families and healthcare providers.

29. Genetic Research: Further research is needed to understand the full spectrum of symptoms and the underlying mechanisms of Ogden syndrome.

30. Clinical Features Table: A clinical features table has been compiled to summarize the various signs and symptoms associated with Ogden syndrome, including facial differences, heart issues, respiratory problems, gastrointestinal symptoms, genitourinary anomalies, growth delays, and skeletal anomalies.

31. OMIM Summary: The Online Mendelian Inheritance in Man (OMIM) has a summary of published research about Ogden syndrome, including references from the medical literature.

32. Orphanet Summary: Orphanet provides a summary about Ogden syndrome that may include information on diagnosis, care, and treatment as well as other resources. Some information is available in languages other than English.

33. GARD Disease Summary: The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition.

34. MONDO Disease Ontology: The MONDO Disease Ontology provides information on Ogden syndrome, including its classification and related terms.

35. Rare Diseases Report: The National Organization for Rare Disorders (NORD) has a detailed report on Ogden syndrome, including its symptoms, causes, and treatment options.

36. Patient Worthy Information: Patient Worthy provides an overview of Ogden syndrome, including its symptoms, causes, diagnosis, and treatment options.

37. NCBI PMC Articles: The National Center for Biotechnology Information (NCBI) has several PMC articles discussing Ogden syndrome in detail, including biochemical and cellular analyses.

38. American Journal of Medical Genetics Part A: An article published in the American Journal of Medical Genetics Part A confirms Ogden syndrome as an X-linked recessive fatal disorder due to a recurrent NAA10 variant and reviews the literature.

39. Confirmation of X-linked Recessive Disorder: The confirmation of Ogden syndrome as an X-linked recessive fatal disorder due to a recurrent NAA10 variant has been supported by multiple studies, including an independent recurrence of the Ser37Pro variant.

40. Clinical Course and Expansion of Clinical Signs: The clinical course and expansion of clinical signs of Ogden syndrome have been documented through various studies, providing a comprehensive understanding of the condition.

Understanding Ogden Syndrome

Ogden syndrome, a rare genetic disorder, stems from mutations in the NAA10 gene. This condition, primarily affecting males due to its X-linked recessive inheritance, presents with severe developmental delays, distinct facial features, and serious heart issues. Symptoms like hypotonia, respiratory problems, and gastrointestinal difficulties further complicate the lives of those affected. While females can be carriers, they usually exhibit milder symptoms unless they inherit two mutated copies. Diagnosing this condition requires whole exome sequencing. Currently, there's no cure, and treatment focuses on managing symptoms. Research continues to uncover more about this complex disorder, aiming to improve diagnostic and therapeutic strategies. Understanding and awareness are crucial for supporting affected individuals and their families.