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].

• Coarctation of the Aorta

  García‐Patos, Aplasia cutis associated with coarctation of the aorta: could this be an incomplete form of Adams–Oliver syndrome?, British Journal of Dermatology, 157, 4, (836-837), (2007). [doi.org]

  - 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]

  “Aplasia cutis associated with coarctation of the aorta: could this be an incomplete form of Adams-Oliver syndrome”. Br J Dermatol. vol. 157. 2007. pp. 836-7. [dermatologyadvisor.com]

• Varicella-Zoster Virus Infection

  TORCH infections (toxoplasmosis, rubella, cytomegalovirus, herpes simplex) and varicella-zoster virus infection should be ruled out with the pertinent serologic studies. Skeletal radiography should include evaluation of the skull, hands, and feet. [symptoma.com]

• Pleural Effusion

  We report on a patient with Adams-Oliver syndrome and report new findings: a chylous pleural effusion and juvenile chronic myelogenous leukemia. [ncbi.nlm.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.

• Thrombocytosis

  Claudio Graziano, Michèle David, Pamela Magini, Andrea Superti‐Furga and Marco Seri, An additional family with association of hereditary thrombocytosis and transverse limb deficiency: Confirmation of a rare clinical spectrum, American Journal of Medical [doi.org]

• Occipital Encephalocele

  The present girl had occipital encephalocele, large scalp defects, aplasia cutis congenita, terminal transverse limb defects and bilateral cleft lip and palate. [ncbi.nlm.nih.gov]

• Pleural Effusion

  We report on a patient with Adams-Oliver syndrome and report new findings: a chylous pleural effusion and juvenile chronic myelogenous leukemia. [ncbi.nlm.nih.gov]

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]

(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]

Ancillary sonographic features: presence of a single umbilical artery presence of oligohydramnios 6 Treatment and prognosis The condition is often fatal and incompatible with life (contrary to popular fairy tales). [radiopaedia.org]

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]

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]

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]

The etiology is unknown, and the outcome for the affected fetus is rather uncertain. [dovepress.com]

While the etiology of Adams-Oliver syndrome is unclear, the mode of inheritance may be autosomal dominant (most common), autosomal recessive, or sporadic. Note that this disease manifests in various degrees of severity. [symptoma.com]

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

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]

However prevention is possible and should be the goal. [afrjpaedsurg.org]

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.