Adams-Oliver syndrome
Encyclopedia
Adams–Oliver syndrome is a rare congenital disorder
characterized by defects of the scalp
and cranium (cutis aplasia congenita), transverse defects of the limbs, and mottling of the skin.
, cleft lip and/or palate, abnormal renal system, and mental retardation
are observed in a fraction of affected individuals. Variable defects in blood vessels have also been described, including hypoplastic aortic arch
, middle cerebral artery
, pulmonary arteries. Other vascular abnormalities described in AOS include absent portal vein, portal sclerosis, arteriovenous malformations, abnormal umbilical vein
s, and dilated renal vein
s.
and reduced penetrance
of the disease-causing allele
. Subsequently, it was reported that some cases of AOS appear to have autosomal recessive inheritance, perhaps with somewhat more severe phenotypic effects.
.
So far, the disease-causing genetic defect in AOS has not been definitively identified. In rare cases, AOS can be associated with chromosomal translocation
s. A panel of candidate gene
s (including ALX4
, CART1, MSX1
, MSX2
, P63
, RUNX2
and HOXD13
) have been tested but no disease-causing mutations have been identified.
The combination of two major criteria would be sufficient for the diagnosis of AOS, while a combination of one major and one minor feature would be suggestive of AOS. There is currently no genetic testing that can be performed in order to confirm or rule out this condition.
, leading to long-term disability.
or overall prevalence
of AOS is unknown. Approximately 100 individuals with this disorder have been reported in the medical literature.
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
characterized by defects of the scalp
Scalp
The scalp is the anatomical area bordered by the face anteriorly and the neck to the sides and posteriorly.-Layers:It is usually described as having five layers, which can conveniently be remembered as a mnemonic:...
and cranium (cutis aplasia congenita), transverse defects of the limbs, and mottling of the skin.
Characteristics
One of the specific features of AOS is cutis aplasia congenita (missing hair and/or skin) affecting the posterior part of the skull, with or without an underlying defect of the cranial bone. The size of the lesion is variable and may range from solitary round hairless patches to complete exposure of the cranial contents. There may also be varying degrees of terminal transverse defects (for example, shortened digits) of either the upper extremities, lower extremities, or both. Individuals with AOS may have mild growth deficiency, with height in the lower normal percentiles. The skin is frequently observed to have a mottled appearance (cutis marmorata). Other congenital anomalies, including cardiovascular malformationsCongenital heart defect
A congenital heart defect is a defect in the structure of the heart and great vessels which is present at birth. Many types of heart defects exist, most of which either obstruct blood flow in the heart or vessels near it, or cause blood to flow through the heart in an abnormal pattern. Other...
, cleft lip and/or palate, abnormal renal system, and mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
are observed in a fraction of affected individuals. Variable defects in blood vessels have also been described, including hypoplastic aortic arch
Aortic arch
The arch of the aorta or the transverse aortic arch is the part of the aorta that begins at the level of the upper border of the second sternocostal articulation of the right side, and runs at first upward, backward, and to the left in front of the trachea; it is then directed backward on the left...
, middle cerebral artery
Middle cerebral artery
-External links:*...
, pulmonary arteries. Other vascular abnormalities described in AOS include absent portal vein, portal sclerosis, arteriovenous malformations, abnormal umbilical vein
Umbilical vein
The umbilical vein is a vein present during fetal development that carries oxygenated blood from the placenta to the growing fetus.The blood pressure inside the umbilical vein is approximately 20 mmHg.-Development:...
s, and dilated renal vein
Renal vein
The renal veins are veins that drain the kidney. They connect the kidney to the inferior vena cava.It is usually singular to each kidney, except in the condition "multiple renal veins".It also divides into 2 divisions upon entering the kidney:...
s.
Genetics
AOS was initially described as having autosomal dominant inheritance due to the reports of families with multiple affected family members in more than one generation. The severity of the condition can vary between family members, suggestive of variable expressivityExpressivity
Expressivity is a term used in genetics to refer to variations in a phenotype among individuals carrying a particular genotype. The term can be used to characterize qualitatively or quantitatively the extent of phenotypic variation given a particular genotype. The term is analogous to the...
and reduced penetrance
Penetrance
Penetrance in genetics is the proportion of individuals carrying a particular variant of a gene that also express an associated trait . In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms...
of the disease-causing allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
. Subsequently, it was reported that some cases of AOS appear to have autosomal recessive inheritance, perhaps with somewhat more severe phenotypic effects.
Mechanism
The precise mechanism underlying the congenital abnormalities observed in AOS is unknown. Similar terminal transverse limb anomalies and cardiovascular malformations are seen in animal models of hypoxic insults during the first trimester. Combined with the common association of cardiac and vascular abnormalities in AOS, it has been hypothesized that the spectrum of defects observed in AOS could be due to a disorder of vasculogenesisVasculogenesis
Vasculogenesis is the process of blood vessel formation occurring by a de novo production of endothelial cells.-Process:Though similar to angiogenesis, the two are different in one aspect: The term angiogenesis denotes the formation of new blood vessels from pre-existing ones, whereas...
.
So far, the disease-causing genetic defect in AOS has not been definitively identified. In rare cases, AOS can be associated with chromosomal translocation
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
s. A panel of candidate gene
Candidate gene
A candidate gene is a gene, located in a chromosome region suspected of being involved in the expression of a trait such as a disease, whose protein product suggests that it could be the gene in question...
s (including ALX4
ALX4
Homeobox protein aristaless-like 4 is a protein that in humans is encoded by the ALX4 gene.-Interactions:ALX4 has been shown to interact with Lymphoid enhancer-binding factor 1.-External links:*...
, CART1, MSX1
MSX1
Msh homeobox 1, also known as MSX1, is a protein that in humans is encoded by the MSX1 gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue that produces both TSHß- and a-subunits and...
, MSX2
MSX2
MSX2 may refer to:* Msh homeobox 2, a human gene* The second generation of the MSX home computers...
, P63
TP73L
Tumor protein p63 also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.TP63 also known as the p63 gene was discovered 20 years after the discovery of the p53 tumor suppressor gene and along with p73 constitutes the p53 gene family based on their...
, RUNX2
Runx2
Runt-related transcription factor 2 also known as core-binding factor subunit alpha-1 is a protein that in humans is encoded by the RUNX2 gene RUNX2 is a key transcription factor associated with osteoblast differentiation....
and HOXD13
HOXD13
Homeobox protein Hox-D13 is a protein that in humans is encoded by the HOXD13 gene.This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms...
) have been tested but no disease-causing mutations have been identified.
Diagnosis
The diagnosis of AOS is a clinical diagnosis based on the specific features described above. A system of major and minor criteria was proposed.| Major features | Minor features |
|---|---|
| Terminal transverse limb defects | Cutis marmorata |
| Aplasia cutis congenita | Congenital heart defect |
| Family history of AOS | Vascular anomaly |
The combination of two major criteria would be sufficient for the diagnosis of AOS, while a combination of one major and one minor feature would be suggestive of AOS. There is currently no genetic testing that can be performed in order to confirm or rule out this condition.
Management
Management of AOS is largely symptomatic and aimed at treating the various congenital anomalies present in the individual. When the scalp and/or cranial bone defects are severe, early surgical intervention with grafting is indicated.Prognosis
The overall prognosis is excellent in most cases. However, individuals with more severe scalp and cranial defects may experience complications such as hemorrhage and meningitisMeningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
, leading to long-term disability.
Epidemiology
AOS is a rare genetic disorder and the annual incidenceIncidence
Incidence may refer to:* Incidence , a measure of the risk of developing some new condition within a specified period of time* Incidence , the binary relations describing how subsets meet...
or overall prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
of AOS is unknown. Approximately 100 individuals with this disorder have been reported in the medical literature.