Clinical Guidance

No genotype-phenotype correlations have been identified. Central hypoventilation has only been reported in individuals with ABDS, and high altitude is a suspected contributing factor .

Source: GeneReviews — "HOXA1-Related Disorders"

Diagnostic Criteria

Suggestive Findings

HOXA1-related disorders should be suspected in probands with the following clinical and imaging findings and family history.

Clinical findings

• Ocular motility disorder: horizontal gaze palsy with or without Duane syndrome (also referred to as Duane retraction syndrome)

• Bilateral sensorineural deafness

• Developmental delay

• Intellectual disability

• Central hypoventilation while awake or asleep requiring supplemental oxygen and/or mechanical ventilatory support

• Congenital heart malformations, cerebrovascular malformations

• Facial paresis, vocal cord paresis, and swallowing dysfunction leading to recurrent aspiration and pneumonia

• Seizure disorder

• Neurobehavioral/psychiatric manifestations

Imaging findings

Source: GeneReviews — "HOXA1-Related Disorders"

Differential Diagnosis

Athabascan brain stem dysgenesis syndrome (ABDS), most commonly reported in individuals of Navajo and Apache descent, must be distinguished from overlapping disorders with horizontal gaze palsy, sensorineural deafness, and/or central hypoventilation. Of note, the differential diagnosis of central hypoventilation includes congenital central hypoventilation syndrome (CCHS) and other conditions associated with central hypoventilation in early infancy such as primary neuromuscular, pulmonary, or cardiac disease; brain stem lesion; hypoxic ischemic encephalopathy, asphyxia, infarction, and infection; and severe prematurity (see CCHS, Differential Diagnosis). Bosley-Salih-Alorainy syndrome (BSAS), most commonly reported in individuals from Middle Eastern populations, must be distinguished from overlapping disorders with sensorineural deafness, horizontal gaze palsy, and/or carotid artery anomalies Table 3. Genes of Interest in the Differential Diagnosis of HOXA1-Related Disorders

Management Guidelines

No clinical practice guidelines for HOXA1-related disorders have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a HOXA1-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. HOXA1-Related Disorders: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "HOXA1-Related Disorders"

Clinical Guidance

It seems prudent to avoid high altitude, especially among individuals with ABDS, based on a few case studies , but this needs further study and confirmation. In addition, practical limitations would make avoiding high altitude challenging. Avoid risk factors leading to stroke (lifestyle and drugs).

Source: GeneReviews — "HOXA1-Related Disorders"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "HOXA1-Related Disorders"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. HOXA1-Related Disorders: Recommended Surveillance

Source: GeneReviews — "HOXA1-Related Disorders"