Human HOXA1 Syndromes

Title

Other Names:

Navajo brainstem syndrome; Athabaskan Brainstem Dysgenesis Syndrome; ABDS; Navajo brainstem syndrome; Athabaskan Brainstem Dysgenesis Syndrome; ABDS; Bosley Salih Alorainy syndrome; BSAS; Athabaskan Brainstem Dysgenesis See More

Categories:

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Heart Diseases; Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Heart Diseases; Nervous System Diseases See More

Summary 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]

Last updated: 4/21/2020

Symptoms 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]

Last updated: 4/21/2020

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.

Showing of 8 |

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

Showing of 8 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Cause Cause

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

Last updated: 4/21/2020

Inheritance Inheritance

Human HOXA1 syndromes are inherited in an autosomal recessive pattern.^[2]^[3]^[5] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the gene must be altered to have the condition.

People with autosomal recessive conditions inherit one altered gene from each of their parents. The parents, who each have one gene alteration, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Last updated: 4/21/2020

Diagnosis Diagnosis

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

Last updated: 4/21/2020

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

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

Last updated: 4/21/2020

Statistics Statistics

The exact number of people with Human HOXA1 syndromes is unknown. Only a small number of people with these conditions have been reported in the literature. One estimate suggested that about 1 in 1000 to 1 in 3000 people in the Native American population are born with Human HOXA1 syndromes.^[1]

Last updated: 4/21/2020

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Learn More 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.

News & Events News & Events

News

Rare Disease Day at NIH 2021
March 1, 2021

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References References

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.
Human HOXA1 syndromes. National Organization of Rare Diseases (NORD). Updated 2013; https://rarediseases.org/rare-diseases/human-hoxa1-syndromes/.
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.
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.
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.