Disease Profile

Human HOXA1 Syndromes

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset

Infancy

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ICD-10

-

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other Names (AKA)

Navajo brainstem syndrome; Athabaskan Brainstem Dysgenesis Syndrome; ABDS;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Heart Diseases;

Summary

Human HOXA1 syndromes are very rare disorders present at birth mainly affecting the development of the ears, eyes, and cardiovascular system. The main symptoms include inability to move the eyes to the sides (horizontal gaze paralysis), deafness, and birth defects involving blood flow in and out of the heart. Human HOXA1 syndromes have been described in Native American populations (primarily the Navajo and Apache Indians) and in a few Saudi Arabian and Turkish families. Symptoms may vary by population. Human HOXA1 syndromes are caused by genetic changes (DNA variants) in the HOXA1 gene and inherited in an autosomal recessive pattern. Diagnosis is made based on the symptoms and confirmed by genetic testing. Treatment is based on managing the specific symptoms.[1][2][3][4][5]

Symptoms

The following list includes the most common signs and symptoms in people with Human HOXA1 syndromes. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list also does not include every symptom or feature that has been described in this condition. 

Symptoms may include:[2][5]

  • Horizontal eye movement disorder
  • Profound deafness
  • Inner ear abnormalities
  • Blood vessel defects or abnormalities involving blood flow to and from the heart
  • Breathing abnormalities
  • Facial weakness or asymmetry

The symptoms of Human HOXA1 syndromes are present in infancy. Some people with this condition have been reported to have intellectual and motor delays, and autistic-like behavior. Because this condition is so rare, not much is understood about how the symptoms change over time.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
1%-4% of people have these symptoms
Central hypoventilation
0007110
Delayed gross motor development
Delayed motor skills
0002194
Internal carotid artery hypoplasia
Decreased size of internal carotid artery
Small internal carotid artery

[ more ]

0005290
Seizure
0001250
Sensorineural hearing impairment
0000407
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Duane anomaly
0009921
Horizontal supranuclear gaze palsy
0007817

Cause

Human HOXA1 syndromes are caused by genetic changes (DNA variants) in the HOXA1 gene.[2][5]

Diagnosis

Human HOXA1 syndromes are diagnosed based on a clinical examination, the symptoms, and confirmed by genetic testing.[2]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

Treatment for Human HOXA1 syndromes is based on managing the symptoms. Some children may require breathing support, especially while sleeping. Some of the specialists that may be involved in the care of someone with a Human HOXA1 syndrome include:[2][3]

  • Pediatricians
  • Surgeons
  • Cardiologists (heart specialists)
  • Pulmonologists (lung and breathing specialists)
  • Dental specialists
  • Speech pathologists
  • Audiologists (specialists who assess and treat hearing problems)
  • Ophthalmologists (eye specialists)
  • Developmental and behavioral specialists

Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Human HOXA1 Syndromes. Click on the link to view a sample search on this topic.

References

  1. Higley MJ, Walkiewicza TW, Millera JH, Currana JG, Towbin RB. Bilateral complete labyrinthine aplasia with bilateral internal carotid artery aplasia, developmental delay, and gaze abnormalities: a presumptive case of a rare HOXA1 mutation syndrome. AJNR Am J Neuroradiol. Feb 2011; 32(2):E23-E25. https://pubmed.ncbi.nlm.nih.gov/20075099.
  2. Human HOXA1 syndromes. National Organization of Rare Diseases (NORD). Updated 2013; https://rarediseases.org/rare-diseases/human-hoxa1-syndromes/.
  3. Tischfield MA, Bosley TM, Salih MAM, Alorainy IA, Sener EC, Nester MJ, Oystreck DT, Chan W-C, Andrews C, Erickson RP, Engle EC. Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development. Nature Genetics. Oct 2005; 37(10):1035-1037. https://pubmed.ncbi.nlm.nih.gov/16155570.
  4. Bosley TM, Salih MA, Alorainy IA, Oystreck DT, Nester M, at al. Clinical characterization of the HOXA1 syndrome BSAS variant. Neurology. Sept 18, 2007; 69(12):1245-1253. https://pubmed.ncbi.nlm.nih.gov/17875913.
  5. Bosley TM, Alorainy IA, Salih MA, Aldhalaan HM, Abu-Amero KK, Oystreck DT et al. The Clinical Spectrum of Homozygous HOXA1 Mutations. Am J Med Genet A. 2008 May 15; 146A(10): 1235–1240. May 15, 2008; 146A(10):1235-1240.