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Disease Profile

Autosomal dominant deafness-onychodystrophy 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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.8

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.

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)

Deafness and onychodystrophy, dominant form; Familial ectodermal dysplasia with sensori-neural deafness and other anomalies; DDOD;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Nervous System Diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 79499

Definition
Dominant deafness-onychodystrophy (DDOD) syndrome is a multiple congenital anomalies syndrome characterized by congenital hearing impairment, small or absent nails on the hands and feet, and small terminal phalanges.

Epidemiology
The prevalence is unknown but it has been reported in 22 individuals from ten families to date.

Clinical description
The main clinical characteristics of DDOD syndrome are severe sensorineural hearing loss or deafness and onychodystrophy (small or absent fingernails and toenails, sometimes limited to the nails of the first and fifth digits). Brachydactyly, long, finger-like or tri-phalangeal thumbs as well as conical, hypoplastic teeth or oligodontia (see this term) have also been reported in several patients. Syndactyly, minor facial dysmorphism (mild hypotelorism, deep set eyes and midface hypoplasia), and epilepsy have been seen in individual cases. Unlike DOORS syndrome (see this term), DDOD patients follow a normal development and have normal intelligence.

Etiology
DDOD syndrome is caused, in some cases, by heterozygous mutations in the ATP6V1B2 gene (8p21.3) encoding a vacuolar ATPase (V-ATPase) involved in protein translocation. It is at present unknown whether there can be genetic heterogeneity or not, as not all known families have been tested.

Diagnostic methods
Diagnosis is based on the presence of characteristic clinical findings. X-rays of the hands and feet and a brain stem auditory evoked response (BAER) test for hearing loss should be performed. Molecular genetic testing identifying a ATP6V1B2 mutation may confirm the diagnosis but as it is at present uncertain whether DDOD syndrome is genetically heterogeneous, the absence of a mutation will not mean that a diagnosis of DDOD syndrome is incorrect.

Differential diagnosis
The main differential diagnosis is DOORS syndrome and Coffin-Siris syndrome (see these terms). The limb anomalies seen in DDOD syndrome can also be found in several other entities including Zimmermann-Laband syndrome, Adams-Oliver syndrome, Temple-Baraitser syndrome and progeroid syndrome, Petty type (see these terms).

Antenatal diagnosis
Prenatal diagnosis of DDOD syndrome has not been performed to date.

Genetic counseling
DDOD syndrome is inherited autosomal dominantly so if the clinical diagnosis has been established reliably, genetic counseling is possible.

Management and treatment
Treatment is supportive and involves special education for the hearing impaired as well as regular follow-up. Corrective surgery is in principle possible for those with syndactyly, although generally not necessary.

Prognosis
The disease is not life threatening. The main influence on quality of life is hearing loss.

Visit the Orphanet disease page for more resources.

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
Severe sensorineural hearing impairment
0008625
30%-79% of people have these symptoms
Absent toenail
0001802
Oligodontia
Failure of development of more than six teeth
0000677
Triphalangeal thumb
Finger-like thumb
0001199
5%-29% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Absent fifth fingernail
Absent nail of fifth finger
0200104
Absent thumbnail
0012554
Aplasia cutis congenita
Absence of part of skin at birth
0001057
Conical tooth
Cone shaped tooth
Shark tooth

[ more ]

0000698
Dolichocephaly
Long, narrow head
Tall and narrow skull

[ more ]

0000268
High forehead
0000348
Hypoplastic toenails
Underdeveloped toenails
0001800
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Poor speech
0002465
Seizure
0001250
Selective tooth agenesis
0001592
Short thumb
Short thumbs
Small thumbs

[ more ]

0009778
Small, conical teeth
Small, cone shaped teeth
0200141
Percent of people who have these symptoms is not available through HPO
Anonychia
Absent nails
Aplastic nails

[ more ]

0001798
Autosomal dominant inheritance
0000006
Brachydactyly
Short fingers or toes
0001156
Congenital onset
Symptoms present at birth
0003577
Hidrotic ectodermal dysplasia
0007529
Nail dystrophy
Poor nail formation
0008404
Sensorineural hearing impairment
0000407
Small nail
Small nails
0001792
Toe syndactyly
Fused toes
Webbed toes

[ more ]

0001770

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.

Organizations Supporting this Disease

    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.

    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 Autosomal dominant deafness-onychodystrophy syndrome. Click on the link to view a sample search on this topic.