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Adams-Oliver syndrome

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Other Names:
Limb scalp and skull defects; AOS; Congenital scalp defects with distal limb anomalies; Limb scalp and skull defects; AOS; Congenital scalp defects with distal limb anomalies; Congenital scalp defects with distal limb reduction anomalies; Limb, scalp and skull defects; Adams Oliver syndrome See More
Categories:
Adams-Oliver syndrome (AOS) is a rare disease characterized by an abnormality of skin development (areas of missing skin on the scalp called aplasia cutis congenita) and malformations of the hands and feet (terminal transverse limbs defects). The aplasia cutis may involve only the skin or include the skull under the skin. The terminal transverse limb defects may include webbed fingers or toes (syndactyly) and short or missing fingers or toes (brachydactyly or oligodactyly, respectively). Other signs and symptoms may include additional skeletal abnormalities of the limbs; cutis marmorata telangiectatica congenita (a blood vessel disorder); pulmonary hypertension; heart defects; and neurological problems.[1] Severity can vary greatly among people with the syndrome and may be lethal in some cases.[2] AOS is caused by mutations in any of six known genes. It may be inherited in an autosomal dominant or autosomal recessive manner, depending on the genetic cause. In some cases, the genetic cause is unknown.[1] Treatment depends on the severity and specific features in each person, and often involves a team of specialists.[3]
Last updated: 3/13/2017

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.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Absent hand 0004050
Absent toe 0010760
Aplasia cutis congenita
Absence of part of skin at birth
0001057
Calvarial skull defect
Cranial defect
Skull defect
[ more ] 		0001362
Cutis marmorata 0000965
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Sparse hair 0008070
30%-79% of people have these symptoms
Abnormal pulmonary valve morphology 0001641
Abnormality of the metacarpal bones
Abnormality of the long bone of hand
0001163
Brachydactyly
Short fingers or toes
0001156
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Finger syndactyly 0006101
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Microphthalmia
Abnormally small eyeball
0000568
Pulmonary artery atresia 0004935
Short distal phalanx of finger
Short outermost finger bone
0009882
Split hand
Claw hand
Claw hand deformities
Claw hands
Claw-hand deformities
Split-hand
[ more ] 		0001171
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Talipes 0001883
Tetralogy of Fallot 0001636
5%-29% of people have these symptoms
Absent fingernail 0001817
Alopecia
Hair loss
0001596
Aplastic/hypoplastic toenail
Absent/small toenails
Absent/underdeveloped toenails
[ more ] 		0010624
Arteriovenous malformation 0100026
Ascites
Accumulation of fluid in the abdomen
0001541
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Congenital hepatic fibrosis
Excessive buildup of connective tissue and scarring of liver at birth
0002612
EEG abnormality 0002353
Encephalocele 0002084
Esophageal varix
Enlarged vein in esophagus
0002040
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Hemiparesis
Weakness of one side of body
0001269
Hypertonia 0001276
Hypoplastic fingernail
Small fingernail
Underdeveloped fingernail
[ more ] 		0001804
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Leukopenia
Decreased blood leukocyte number
Low white blood cell count
[ more ] 		0001882
Periventricular leukomalacia 0006970
Porencephalic cyst
Cavity within brain
0002132
Portal hypertension 0001409
Premature birth
Premature delivery of affected infants
Preterm delivery
[ more ] 		0001622
Pulmonary arterial hypertension
Increased blood pressure in blood vessels of lungs
0002092
Seizure 0001250
Thrombocytopenia
Low platelet count
0001873
Percent of people who have these symptoms is not available through HPO
Aortic valve stenosis
Narrowing of aortic valve
0001650
Aplasia cutis congenita on trunk or limbs 0007589
Aplasia cutis congenita over posterior parietal area 0007590
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ] 		0001631
Autosomal dominant inheritance 0000006
Bicuspid aortic valve
Aortic valve has two leaflets rather than three
0001647
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Cortical dysplasia 0002539
Esotropia
Inward turning cross eyed
0000565
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Global developmental delay 0001263
Hypertension 0000822
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Hypoplastic left heart
Underdeveloped left heart
0004383
Imperforate hymen 0030011
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Muscular hypotonia
Low or weak muscle tone
0001252
Pachygyria
Fewer and broader ridges in brain
0001302
Polymicrogyria
More grooves in brain
0002126
Pulmonary artery stenosis
Narrowing of lung artery
0004415
Pulmonic stenosis
Narrowing of pulmonic valve
0001642
Small nail
Small nails
0001792
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot
[ more ] 		0001762
Toe syndactyly
Fused toes
Webbed toes
[ more ] 		0001770
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Ventriculomegaly 0002119
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Last updated: 7/1/2020
Adams-Oliver syndrome (AOS) may be inherited in an autosomal dominant or autosomal recessive manner, depending on the gene mutation.[1]

When AOS is caused by a mutation in the ARHGAP31, DLL4, NOTCH1, or RBPJ gene, the syndrome is inherited in an autosomal dominant manner.[1] This means that having a mutation in only one copy of the responsible gene in each cell is enough to cause signs and symptoms of AOS. In most cases, a person inherits the mutated gene from a parent with the syndrome. In other cases, the mutation is sporadic, which means that it occurs for the first time in a person with no family history of AOS. When a person with an autosomal dominant form of AOS has children, each child has a 50% (1 in 2) chance to inherit the disease-causing mutation.

When AOS is caused by mutations in the DOCK6 or EOGT gene, the syndrome is inherited in an autosomal recessive manner.[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. People with AOS inherit one mutated copy of the gene from each parent. If the parent does not have AOS, then he or she is referred to as a carrier. Carriers of an autosomal recessive disease typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive disease have children, each child has a 25% (1 in 4) chance to be affected, a 50% (1 in 2) chance to be an unaffected carrier like each parent, and a 25% chance to be unaffected AND not be a carrier.
Last updated: 3/13/2017
Adams-Oliver syndrome (AOS) should be suspected when the following signs and symptoms are present:[4]
  • Aplasia cutis congenital, which may be severe and includes the skull under the area of the missing scalp, or mild and characterized by hairless patches of different size
  • Terminal transverse limb defects (TTLD) spectrum, which can include small distal phalanges, short bones of the tips of the fingers or toes (distal phalanges), short and webbed fingers (brachysyndactyly), or absence of some fingers
  • Heart and vascular defects
The diagnosis of Adams-Oliver syndrome is established with one of the following:[4]
  • The clinical findings of both aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD)
  • Either ACC or TTLD and a first-degree relative with findings consistent with AOS
  • Either ACC or TTLD and either a mutation of an AOS-related gene
In some cases, it may be possible to detect defects of the skull and/or limbs before birth (during the prenatal period) through the ultrasound.[5]
Last updated: 3/13/2017
The long-term outlook (prognosis) for people with Adams-Oliver syndrome (AOS) varies depending on the specific signs and symptoms present in each person and the degree of severity of these signs and symptoms. In some cases the prognosis is excellent, although surgery often is needed to close the skull or scalp defects that may expose the brain.[6] It seems likely that mild forms (for example, those with only skin and/or skeletal abnormalities) are associated with a better prognosis and a normal life expectancy.[7] However, when people with AOS have congenital heart defects or severe problems with other organs or systems, the condition can be very severe.[8][7]
Last updated: 3/13/2017

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

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

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

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

  • Genetics Home Reference (GHR) contains information on Adams-Oliver syndrome. This website is maintained by the National Library of Medicine.
  • More information on limb abnormalities can be found at the following link from MedlinePlus, the National Library of Medicine Web site designed to help you research your health questions.
  • 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 Adams-Oliver syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • What is the life expectancy of children with this genetic disorder? See answer


  1. Adams-Oliver syndrome. Genetics Home Reference. November, 2015; http://ghr.nlm.nih.gov/condition/adams-oliver-syndrome.
  2. Seo JK & cols. A Case of Adams-Oliver Syndrome. Ann Dermatol. February, 2010; 22(1):96-98. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883411/.
  3. Adams Oliver syndrome. Orphanet. November, 2006; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=974.
  4. Lehman A, Wuyts W & Patel MS. Adams-Oliver Syndrome. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/books/NBK355754/?report=reader.
  5. Adams Oliver syndrome. NORD. 2009; https://rarediseases.org/rare-diseases/adams-oliver-syndrome/.
  6. Beryl R. Benacerraf. Limb Abnormalities. Ultrasound of Fetal Syndromes, Second Edition. Canada: Elsevier, Inc; 2008; 223.
  7. Nadia Iftikhar et. al. Adams-Oliver Syndrome. Journal of the College of Physicians and Surgeons Pakistan. 2014; 24 (Special Supplement 2):S76-S77.
  8. Southgate L, et. al. Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome With Variable Cardiac Anomalies. Circ Cardiovasc Genet. August, 2015; 8(4):572-581.