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Disease Profile

Xia-Gibbs syndrome

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.

Unknown

Age of onset

#N/A

ICD-10

#N/A

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)

AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome; Autosomal dominant intellectual disability 25

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Xia-Gibbs syndrome is a rare disorder of intellectual disability.[1][2][3] People with this syndrome usually present with developmental delay (especially delays in speech), low muscule tone (hypotonia), failure to thrive, mildly unusual facial features (broad forehead, widely-spaced eyes (hypertelorism), big and low-set ears, flat nasal bridge, and thin upper lip), and breathing difficulties when sleeping (sleep apnea). The sleep apnea may be due to a collapse of the airway when breathing (tracheomalacia). Other signs and symptoms may include autistic features, seizures, lack of coordination (ataxia), behavioral problems, crossed-eyes (strabismus), and an abnormal lateral curvature of the spine (scoliosis).[1][4][3] Males usually have more severe symptoms than females. Brain MRI may show several structural brain defects, such as thinning of the corpus callosum and posterior fossa cysts.[1][4]

Xia-Gibbs syndrome is caused by variants (mutations) in the AHDC1 gene.[2] Inheritance is autosomal dominant but all reported cases to date have been due to new mutations (de novo), in individuals with no family history.[5][4][3] Treatment and management is supportive, and ideally, should involve several specialists. This may include careful monitoring of the airways, continuous positive airway pressure at night, frequent growth assessments, physical therapy and early interventions to maximize developmental potential.[4]

Symptoms

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
80%-99% of people have these symptoms
Global developmental delay
0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Muscular hypotonia
Low or weak muscle tone
0001252
30%-79% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Ataxia
0001251
Delayed ability to walk
0031936
Expressive language delay
0002474
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

[ more ]

0001388
Obstructive sleep apnea
0002870
Seizure
0001250
Upbeat nystagmus
0011477
Upper airway obstruction
0002781
5%-29% of people have these symptoms
Autism
0000717
Cerebral visual impairment
0100704
Craniosynostosis
0001363
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye

[ more ]

0000490
Delayed myelination
0012448
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
EEG abnormality
0002353
Esotropia
Inward turning cross eyed
0000565
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Laryngomalacia
Softening of voice box tissue
0001601
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Mild myopia
0025573
Protruding ear
Prominent ear
Prominent ears

[ more ]

0000411
Respiratory failure requiring assisted ventilation
0004887
Retrocerebellar cyst
0006951
Scoliosis
0002650
Small earlobe
Small earlobes
0000385
Snoring
0025267
Tracheomalacia
Floppy windpipe
0002779
Uplifted earlobe
Lobe, uplifted
Upturned earlobe

[ more ]

0009909
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Simplified gyral pattern
0009879

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Social Networking Websites

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

In-Depth Information

  • 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 Xia-Gibbs syndrome. Click on the link to view a sample search on this topic.

References

  1. Xia F, Bainbridge MN, Tan TY, et al. De Novo Truncating Mutations in AHDC1 in Individuals with Syndromic Expressive Language Delay, Hypotonia, and Sleep Apnea. American Journal of Human Genetics. 2014; 94(5):784-789. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067559/.
  2. AHDC1 gene. Genetics Home Reference. 2018; https://ghr.nlm.nih.gov/gene/AHDC1.
  3. Yang H, Douglas G, Monaghan KG, et al. De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif-containing protein 1 are associated with intellectual disability and developmental delay. Cold Spring Harbor Molecular Case Studies. 2015; 1(1):https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850891/.
  4. Jiang Y, Wangler MF, McGuire AL & cols. The phenotypic spectrum of Xia-Gibbs syndrome. Am J Med Genet A. June, 2018; 176(6):1315-1326. https://www.ncbi.nlm.nih.gov/pubmed/29696776.
  5. Xia-Gibbs syndrome. OMIM. 2014; https://www.omim.org/entry/615829.