Adams-Oliver syndrome is a genetic disorder defined by aplasia cutis congenita and defects of the skull and limbs [1] [2]. While the etiology of Adams-Oliver syndrome is unclear [1], the mode of inheritance may be autosomal dominant (most common), autosomal recessive, or sporadic [3] [4]. Note that this disease manifests in various degrees of severity [5].

Aplasia cutis congenita in affected patients is characterized by bald areas on the scalp that are remarkable for scarring and ulcers. The underlying cutaneous vessels may be abnormally dilated and prone to hemorrhage [1]. The scalp lesions heal spontaneously in infancy.

Affected patients may exhibit missing segments in their skull and malformation of their hands, feet, and/or digits [1]. Specifically, some or all bones in affected areas may be hypoplastic or absent. These findings are typically more pronounced in the lower extremities.

Adams-Oliver syndrome may include intracranial features ranging from periventricular calcifications to cortical dysplasia and other severe manifestations [1] [6]. Additionally, cardiac manifestations such as septal defects and aortic coarctation may be present [1]. Moreover, some patients exhibit renal anomalies, cryptorchidism, cleft palate, abnormal lymphatics, and so forth [1]. A congenital hepatic shunt has been described in the literature [1] [7]. A developmental delay may also be noticeable [1].

Scalp lesions may bleed and lead to infection and even meningitis. Also, affected individuals experience physical disabilities as a consequence of deformed extremities. Finally, long-term sequelae from cardiac involvement may result in heart failure and other comorbidities.

Inspection of the scalp allows the clinician to visualize atrophic hairless plaques which are commonly located on the vertex of the head [8]. Also, digits appear to be short and telangiectasias may be observed on the limbs and abdomen [9].

• Epilepsy

  Now, he is 3 years old, and has microcephaly, moderate mental retardation, left spastic hemiplegia, and epilepsy. [ncbi.nlm.nih.gov]

  Review of these cases is initially suggestive of an increased frequency of both central nervous system involvement as well as epilepsy in the autosomal recessive variant of AOS. [doi.org]

• Weakness

  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 [rarediseases.info.nih.gov]

• Congestive Heart Failure

  Signs and Symptoms of Congestive Heart Failure: Successful Treatment with Coil Embolization J Kosutic, P Minic, A Sovtic, S Prijic Journal of Vascular and Interventional Radiology 18 (2), 299-302, 2007 6 2007 Levosimendan treatment of severe acute congestive [scholar.google.com]

  A moderately-sized defect may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body (congestive heart failure). [rarediseases.org]

• Fever

  Because preventing fever after TTM is relatively benign and fever may be associated with harm, preventing fever is suggested. [eccguidelines.heart.org]

  Because of fever and unfavorable general conditions and with high suspicion of osteomyelitis, the patient was moved to the pediatric ward. [advbiores.net]

• Asymptomatic

  Individuals who are carriers for the recessive type of Adams-Oliver syndrome do not have any symptoms (asymptomatic) and do not know they are carriers unless they have had a child with the syndrome. [encyclopedia.com]

  Probands are marked by the black arrows, and asymptomatic carriers are indicated with black dots. For de novo mutations, paternity was confirmed by microsatellite analysis (data not shown). + indicates wild-type allele; and –, mutant allele. [doi.org]

• Heart Disease

  Also, our patient had congenital heart disease, confirming that heart lesions are a manifestation in this syndrome. The major manifestations of this disorder are summarized. [ncbi.nlm.nih.gov]

  - sometimes: congenital heart disease (20%) (tetralogy of Fallot, pulmonary atresia, coarctation of the aorta), esophageal atresia, hepato-portal sclerosis, congenital cataract and other ocular anomalies (DOCK6 mutations), retineal vascularization anomaly [sites.uclouvain.be]

  Vojnosanitetski pregled 68 (11), 979-984, 2011 5 2011 Low-bandwidth teleconsultations for patients with complex congenital heart diseases J Kosutic, ML Rigby, D Mijin, G Weatherburn, V Jowett, V Vukomanovic, ... [scholar.google.com]

  Congenital heart disease has also been reported in individuals with this condition. The exact cause of the condition is not well-understood. There is extreme variability in the severity of problems between families with AOS. [encyclopedia.com]

• Blister

  It has a documented role in epithelial-cell-matrix interactions in Drosophila, in which deficiency of its ortholog causes wing blistering. [ncbi.nlm.nih.gov]

  […] of cellular processes including intracellular signaling, transcription, and protein stability. 10 Drosophila Eogt mutants display defects in the apical extracellular matrix (aECM), including separation of the epidermis from the chitin layers and wing blistering [doi.org]

• Hyperpigmentation

  Besides these he had bilateral clubfoot, cortical fissure and nail hypoplasia in the hands, scrotal hyperpigmentation and generalized cutis marmorata telangiectatica congenita. He was operated on the 3rd day of life. [ncbi.nlm.nih.gov]

• Skin Thickening

  The lesions of cutis marmorata may fade with time during first year of life due to skin thickening and maturation. Copyright 1999-2015 Indian Pediatrics [indianpediatrics.net]

• Foot Deformity

  Allen, Visual Diagnosis: A Baby with a Scalp Lesion, Rash, and Left-Foot Deformity, Pediatrics in Review, 38, 6, (e20), (2017). Krystal M. Jones, Annika Silfvast‐Kaiser, David R. Leake, Lucia Z. Diaz and Moise L. [doi.org]

• Seizure

  Recently reports suggest an increased frequency of seizures and central nervous system involvement in autosomal recessive Adams-Oliver syndrome. [ncbi.nlm.nih.gov]

  CMTC and cardiac malformations are common (20%), while ophthalmological abnormalities occur in 2 Neurological deficits are uncommon, but more severe vascular phenotypes may have developmental problems and seizures. 3 Different inheritance patterns are [casereports.bmj.com]

  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 [rarediseases.info.nih.gov]

• Global Developmental Delay

  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 [rarediseases.info.nih.gov]

The diagnosis is based on the physical exam, a thorough family history, and the appropriate studies.

TORCH infections (toxoplasmosis, rubella, cytomegalovirus, herpes simplex) and varicella-zoster virus infection should be ruled out with the pertinent serologic studies [1].

Skeletal radiography should include evaluation of the skull, hands, and feet [8]. Typically acrania is observed corresponding to sites of scalp lesions [1]. Additionally, other skeletal findings may include a partial or complete absence of bones in limbs and digits [1] [8].

Findings on computed tomography (CT) of the head may include features such as periventricular calcifications and abnormalities of the sulci and gyri [1]. Note that a head CT will also identify skull defects.

Magnetic resonance imaging (MRI) of the brain may display a hypoplastic corpus callosum [1], cystic cortical dysplasia [9], sinus thrombosis [1], and/or infarcts [10]. Very importantly, an MRI angiogram demonstrates the presence of extrahepatic portosystemic shunts [1].

Patients with Adams-Oliver syndrome also warrant a cardiac assessment with echocardiography and possibly cardiac catheterization [1] [8] [9]. Chest studies with radiography and CT scanning with contrast are also performed to evaluate for the presence of arteriovenous malformations (AVM) [9].

Other indicated imaging modalities include Doppler ultrasonography to evaluate for vasculature malformations [9], intravenous pyelography, abdominal ultrasound, and pelvic ultrasound [8]. Finally, skin biopsy with special staining could also be useful [8].

Routine prenatal ultrasonography may detect the range of the above deformities in an affected fetus.

Management and treatment Limb and scalp defects require orthopedic treatment. Management requires a comprehensive multidisciplinary approach. The documents contained in this web site are presented for information purposes only. [orpha.net]

Mortality rates associated with both conservative treatment and with surgical repair are around 20% [3]. [pfond.cmmt.ubc.ca]

Both treatment modalities proved successful in these cases. [ncbi.nlm.nih.gov]

(Outcomes/Resolutions) The long term prognosis of Adams Oliver Syndrome is not described adequately due to the limited number of cases reported worldwide and limited extended follow-up of affected individuals However, the prognosis depends on the major [dovemed.com]

DOCK6 mutations were strongly associated with structural brain abnormalities, ocular anomalies, and intellectual disability, thus suggesting that DOCK6-linked disease represents a variant of AOS with a particularly poor prognosis. © 2015 WILEY PERIODICALS [ncbi.nlm.nih.gov]

Overall the prognosis for children with AOS is excellent. Inheritance patterns and prenatal diagnosis Is there support? There is no support group for Adams-Oliver syndrome in the UK. [cafamily.org.uk]

The etiology of this syndrome has remained largely unknown but defective Notch signaling during vascular formation has been suggested. Here we describe a sporadic Japanese newborn case with clinically diagnosed AOS. [ncbi.nlm.nih.gov]

Etiology The etiopathogenesis remains unclear. Genetic counseling Most cases are transmitted as an autosomal dominant trait, but some show autosomal recessive transmission with familial or sporadic occurrence. [orpha.net]

Summary Epidemiology The prevalence is unknown. Clinical description The severity of the disorder varies greatly among affected individuals. [orpha.net]

Sirenomelia: an epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research, and literature review. Am J Med Genet C Semin Med Genet. 2011;157c:358–73. [degruyter.com]

While pulmonary hypertension is usually not associated with AOS, the abnormal endothelial regulation of vascular tone seen in the pulmonary vasculature may enhance current pathophysiologic concepts of vascular abnormalities in AOS. [ncbi.nlm.nih.gov]

The underlying pathophysiologic mechanism is still unknown. References Adams FM, Oliver CP (1945,). "Hereditary deformities in man due to arrested development". J Hered. 36 : 3–7. Check date values in: |year= ( help ) Whitley CB, Gorlin RJ (1991). [wikidoc.org]

Pathophysiology Many genes have been implicated in the development of AOS. [dermatologyadvisor.com]

Skin grafting is the safest way, preventing hemorrhage and infection, in the operative treatment of aplasia cutis in these babies. [ncbi.nlm.nih.gov]

"Ultimately, this knowledge may lead us to develop better ways of treating children with these kind of abnormalities, and one day we may even be able to prevent them from developing in the first place." [news-medical.net]

Since povidone-iodine dressings could lead to wound desiccation, they should be avoided to prevent fatal complication of bleeding [3]. [pfond.cmmt.ubc.ca]

With conservative therapy to prevent secondary infection and consequent tissue damage, most small defects of scalp heal well during the first few months of life. Larger and obvious scars can be treated with plastic surgical reconstruction. [indianpediatrics.net]

1. Pérez-García C, Martín YR, del Hoyo AA, Rodríguez CM, Domínguez MC. Adams-Oliver Syndrome with Unusual Central Nervous System Findings and an Extrahepatic Portosystemic Shunt. Pediatric Rep. 2017;9(2):7211.
2. Adams FH, Oliver CR. Hereditary deformities in man: due to arrested development. J Hered. 1945;36:3-7.
3. McGoey RR, Lacassie Y. Adams-Oliver syndrome in siblings with central nervous system findings, epilepsy, and developmental delay: refining the features of a severe autosomal recessive variant. Am J Med Genet. 2008;146A(4):488–491.
4. Koiffmann CP, Wajntal A, Huyke BJ, Castro RM. Congenital scalp skull defects with distal limb anomalies (Adams-Oliver syndrome--McKusick 10030): further suggestion of autosomal recessive inheritance. Am J Med Genet. 1988;29(2):263–268.
5. Renfree KJ, Dell PC. Distal limb defects and aplasia cutis: Adams-Oliver syndrome. J Hand Surg Am. 2016;41(7): e207-e210.
6. Balasubramanian M, Collins AL. Aplasia cutis congenita, terminal limb defects and periventricular leukomalacia in one sibling with minor findings in the other-probable autosomal recessive Adams-Oliver Syndrome. Eur J Med Genet. 2009;52(4):234-238.
7. Gallego C, Miralles M, Marin C, et al. Congenital hepatic shunts. Radiographics. 2004;24(3):755-772.
8. Bakry O, Attia A, El Shafey EN. Adams-Oliver Syndrome. A case with isolated aplasia cutis congenita and skeletal defects. J Dermatol Case Rep. 2012;6(1):25-28.
9. D'Amico A, Melis D, D'Arco F, et al. Adams Oliver syndrome: Description of a new phenotype with cerebellar abnormalities in a family. Pol J Radiol. 2013; 78(4):83-87.
10. Stittrich AB, Lehman A, Bodian DL, et al. Mutations in NOTCH1 cause Adams-Oliver syndrome. Am J Hum Genet 2014;95(3):275-284.