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Human HOXA1 syndromes(ABDS)

MedGen UID:
330410
Concept ID:
C1832215
Disease or Syndrome
Synonyms: ABDS; Athabaskan brainstem dysgenesis; Athabaskan brainstem dysgenesis syndrome; Navajo brainstem syndrome
SNOMED CT: Athabaskan brainstem dysgenesis syndrome (720518006); Athabascan brainstem dysgenesis syndrome (720518006); Navajo brainstem syndrome (720518006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): HOXA1 (7p15.2)
 
Monarch Initiative: MONDO:0011099
OMIM®: 601536
Orphanet: ORPHA69739

Definition

Homozygous loss-of-function mutations in the HOXA1 gene result in disorders with variable phenotypic expressivity that span a spectrum. Two related, but somewhat distinctive, phenotypes have been described in different populations: the Athabaskan brainstem dysgenesis syndrome (ABDS) in Native Americans, and Bosley-Salih-Alorainy syndrome (BSAS) in individuals from the Middle East, including Turkey and Saudi Arabia. Features common to both disorders include Duane retraction syndrome with variable gaze palsies, sensorineural deafness associated with inner ear abnormalities, and delayed motor development. More variable features, observed in both disorders, include conotruncal cardiac malformations, cerebral vascular malformations, and impaired intellectual development with autism. Unique to ABDS are central hypoventilation, often resulting in early death, facial weakness, and more severe cognitive deficits. These features are thought to be due to a more severe malformation of the hindbrain in ABDS compared to BSAS (summary by Tischfield et al., 2005). [from OMIM]

Clinical features

From HPO
Internal carotid arteries, hypoplasia of
MedGen UID:
383757
Concept ID:
C1855736
Finding
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Central hypoventilation
MedGen UID:
812169
Concept ID:
C3805839
Finding
Duane retraction syndrome
MedGen UID:
4413
Concept ID:
C0013261
Disease or Syndrome
Duane syndrome is a strabismus condition clinically characterized by congenital non-progressive limited horizontal eye movement accompanied by globe retraction which results in narrowing of the palpebral fissure. The lateral movement anomaly results from failure of the abducens nucleus and nerve (cranial nerve VI) to fully innervate the lateral rectus muscle; globe retraction occurs as a result of abnormal innervation of the lateral rectus muscle by the oculomotor nerve (cranial nerve III). At birth, affected infants have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction), though the limitations may not be recognized in early infancy. In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. Many individuals with Duane syndrome have strabismus in primary gaze but can use a compensatory head turn to align the eyes, and thus can preserve binocular vision and avoid diplopia. Individuals with Duane syndrome who lack binocular vision are at risk for amblyopia. The majority of affected individuals with Duane syndrome have isolated Duane syndrome (i.e., they do not have other detected congenital anomalies). Other individuals with Duane syndrome fall into well-defined syndromic diagnoses. However, many individuals with Duane syndrome have non-ocular findings that do not fit a known syndrome; these individuals are included as part of the discussion of nonsyndromic Duane syndrome.
Horizontal supranuclear gaze palsy
MedGen UID:
870350
Concept ID:
C4024794
Disease or Syndrome
A supranuclear gaze palsy is an inability to look in a horizontal direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHuman HOXA1 syndromes
Follow this link to review classifications for Human HOXA1 syndromes in Orphanet.

Recent clinical studies

Etiology

Khalilian S, Mohajer Z, Hosseini Imani SZ, Ghafouri-Fard S
Pathol Res Pract 2023 Sep;249:154730. Epub 2023 Jul 29 doi: 10.1016/j.prp.2023.154730. PMID: 37549517
MacKinnon S, Oystreck DT, Andrews C, Chan WM, Hunter DG, Engle EC
Ophthalmology 2014 Jul;121(7):1461-8. Epub 2014 Mar 6 doi: 10.1016/j.ophtha.2014.01.006. PMID: 24612975Free PMC Article
Qu Y, Dang S, Hou P
Clin Chim Acta 2013 Sep 23;424:53-65. Epub 2013 May 10 doi: 10.1016/j.cca.2013.05.002. PMID: 23669186
Schaaf CP, Sabo A, Sakai Y, Crosby J, Muzny D, Hawes A, Lewis L, Akbar H, Varghese R, Boerwinkle E, Gibbs RA, Zoghbi HY
Hum Mol Genet 2011 Sep 1;20(17):3366-75. Epub 2011 May 30 doi: 10.1093/hmg/ddr243. PMID: 21624971Free PMC Article
Ingram JL, Stodgell CJ, Hyman SL, Figlewicz DA, Weitkamp LR, Rodier PM
Teratology 2000 Dec;62(6):393-405. doi: 10.1002/1096-9926(200012)62:6<393::AID-TERA6>3.0.CO;2-V. PMID: 11091361

Diagnosis

Lyu P, Zhai Z, Hao Z, Zhang H, He J
Eur J Clin Invest 2021 Jun;51(6):e13487. Epub 2021 Apr 27 doi: 10.1111/eci.13487. PMID: 33410156
Oystreck DT
J Binocul Vis Ocul Motil 2018 Jan-Mar;68(1):31-33. Epub 2018 Jan 31 doi: 10.1080/2576117X.2017.1416242. PMID: 30196776
Abu-Amero KK, Hagr Aa, Almomani MO, Azad TA, Alorainy IA, Oystreck DT, Bosley TM
Can J Neurol Sci 2014 Jul;41(4):448-51. doi: 10.1017/s0317167100018473. PMID: 24878468
Qu Y, Dang S, Hou P
Clin Chim Acta 2013 Sep 23;424:53-65. Epub 2013 May 10 doi: 10.1016/j.cca.2013.05.002. PMID: 23669186
Rankin JK, Andrews C, Chan WM, Engle EC
J AAPOS 2010 Feb;14(1):78-80. doi: 10.1016/j.jaapos.2009.11.007. PMID: 20227628Free PMC Article

Therapy

Niederreither K, Vermot J, Le Roux I, Schuhbaur B, Chambon P, Dollé P
Development 2003 Jun;130(11):2525-34. doi: 10.1242/dev.00463. PMID: 12702665

Prognosis

Khalilian S, Mohajer Z, Hosseini Imani SZ, Ghafouri-Fard S
Pathol Res Pract 2023 Sep;249:154730. Epub 2023 Jul 29 doi: 10.1016/j.prp.2023.154730. PMID: 37549517
Zhang TJ, Xu ZJ, Wen XM, Gu Y, Ma JC, Yuan Q, Lin J, Zhou JD, Qian J
Leukemia 2022 Oct;36(10):2488-2498. Epub 2022 Jul 29 doi: 10.1038/s41375-022-01659-1. PMID: 35906386

Clinical prediction guides

Zhang TJ, Xu ZJ, Wen XM, Gu Y, Ma JC, Yuan Q, Lin J, Zhou JD, Qian J
Leukemia 2022 Oct;36(10):2488-2498. Epub 2022 Jul 29 doi: 10.1038/s41375-022-01659-1. PMID: 35906386
Lyu P, Zhai Z, Hao Z, Zhang H, He J
Eur J Clin Invest 2021 Jun;51(6):e13487. Epub 2021 Apr 27 doi: 10.1111/eci.13487. PMID: 33410156
MacKinnon S, Oystreck DT, Andrews C, Chan WM, Hunter DG, Engle EC
Ophthalmology 2014 Jul;121(7):1461-8. Epub 2014 Mar 6 doi: 10.1016/j.ophtha.2014.01.006. PMID: 24612975Free PMC Article
Abu-Amero KK, Faletra F, Gasparini P, Parentin F, Pensiero S, Alorainy IA, Hellani AM, Catalano D, Bosley TM
Ophthalmic Genet 2011 Nov;32(4):212-6. Epub 2011 Apr 21 doi: 10.3109/13816810.2011.574186. PMID: 21510772
Ingram JL, Stodgell CJ, Hyman SL, Figlewicz DA, Weitkamp LR, Rodier PM
Teratology 2000 Dec;62(6):393-405. doi: 10.1002/1096-9926(200012)62:6<393::AID-TERA6>3.0.CO;2-V. PMID: 11091361

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