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Adams-Oliver syndrome 6(AOS6)

MedGen UID:
908556
Concept ID:
C4225271
Disease or Syndrome
Synonym: AOS6
 
Gene (location): DLL4 (15q15.1)
 
Monarch Initiative: MONDO:0014703
OMIM®: 616589

Definition

Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies. [from GeneReviews]

Additional descriptions

From OMIM
Adams-Oliver syndrome is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly). In addition, vascular anomalies such as cutis marmorata telangiectatica congenita, pulmonary hypertension, portal hypertension, and retinal hypervascularization are recurrent findings. Congenital heart defects have been estimated to be present in 20% of AOS patients; reported malformations include ventricular septal defects, anomalies of the great arteries and their valves, and tetralogy of Fallot (summary by Stittrich et al., 2014). For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (100300).  http://www.omim.org/entry/616589
From MedlinePlus Genetics
In some cases, people with Adams-Oliver syndrome have neurological problems, such as developmental delay, learning disabilities, or abnormalities in the structure of the brain.

Some affected infants have a condition called cutis marmorata telangiectatica congenita. This disorder of the blood vessels causes a reddish or purplish net-like pattern on the skin. In addition, people with Adams-Oliver syndrome can develop high blood pressure in the blood vessels between the heart and the lungs (pulmonary hypertension), which can be life-threatening. Other blood vessel problems and heart defects can occur in affected individuals.

Abnormalities of the hands and feet are also common in people with Adams-Oliver syndrome. These most often involve the fingers and toes and can include abnormal nails, fingers or toes that are fused together (syndactyly), and abnormally short or missing fingers or toes (brachydactyly or oligodactyly). In some cases, other bones in the hands, feet, or lower limbs are malformed or missing.

Most people with Adams-Oliver syndrome have aplasia cutis congenita, a condition characterized by localized areas of missing skin typically occurring on the top of the head (the skull vertex). In some cases, the bone under the skin is also underdeveloped. Individuals with this condition commonly have scarring and an absence of hair growth in the affected area.

Adams-Oliver syndrome is a rare condition that is present at birth. The primary features are an abnormality in skin development (called aplasia cutis congenita) and malformations of the limbs. A variety of other features can occur in people with Adams-Oliver syndrome.  https://medlineplus.gov/genetics/condition/adams-oliver-syndrome

Clinical features

From HPO
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Syndactyly
MedGen UID:
52619
Concept ID:
C0039075
Congenital Abnormality
Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are referred to as "symphalangism".
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Foot oligodactyly
MedGen UID:
923973
Concept ID:
C4281601
Anatomical Abnormality
A developmental defect resulting in the presence of fewer than the normal number of toes.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Portal hypertension
MedGen UID:
9375
Concept ID:
C0020541
Disease or Syndrome
Increased pressure in the portal vein.
Tricuspid regurgitation
MedGen UID:
11911
Concept ID:
C0040961
Disease or Syndrome
Failure of the tricuspid valve to close sufficiently upon contraction of the right ventricle, causing blood to regurgitate (flow backward) into the right atrium.
Persistent truncus arteriosus
MedGen UID:
52867
Concept ID:
C0041207
Congenital Abnormality
A single arterial trunk arises from the cardiac mass. The pulmonary arteries, aorta and coronary arteries arise from this single trunk with no evidence of another outflow tract.
Esophageal varix
MedGen UID:
5027
Concept ID:
C0014867
Disease or Syndrome
Extreme dilation of the submucusoal veins in the lower portion of the esophagus.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Calvarial skull defect
MedGen UID:
871299
Concept ID:
C4025787
Anatomical Abnormality
A localized defect in the bone of the skull resulting from abnormal embryological development. The defect is covered by normal skin. In some cases, skull x-rays have shown underlying lytic bone lesions which have closed before the age of one year.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Cutis marmorata
MedGen UID:
78093
Concept ID:
C0263401
Disease or Syndrome
A reticular discoloration of the skin with cyanotic (reddish-blue appearing) areas surrounding pale central areas due to dilation of capillary blood vessels and stagnation of blood within the vessels. Cutis marmorata generally occurs on the legs, arms and trunk and is often more severe in cold weather.
Hypoplastic toenails
MedGen UID:
332409
Concept ID:
C1837279
Finding
Underdevelopment of the toenail.
Aplasia cutis congenita of scalp
MedGen UID:
343411
Concept ID:
C1855698
Congenital Abnormality
A developmental defect resulting in the congenital absence of skin on the scalp.

Professional guidelines

PubMed

Browning JC
Dermatol Ther 2013 Nov-Dec;26(6):439-44. doi: 10.1111/dth.12106. PMID: 24552406

Recent clinical studies

Etiology

van Nisselrooij AEL, Herling L, Clur SA, Linskens IH, Pajkrt E, Rammeloo LA, Ten Harkel ADJ, Hazekamp MG, Blom NA, Haak MC
Prenat Diagn 2021 May;41(6):754-765. Epub 2021 Feb 26 doi: 10.1002/pd.5907. PMID: 33480066Free PMC Article
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Ophthalmol Retina 2019 Sep;3(9):791-801. Epub 2019 May 1 doi: 10.1016/j.oret.2019.03.025. PMID: 31147303
Salih MA, Murshid WR, Al-Salman MM, Abdel-Gader AG, Al-Jarallah AA, Alorainy IA, Hassan HH, Kentab AY, Van Maldergem L, Othman SA, El-Desouki MI, Elgamal EA
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Pousti TJ, Bartlett RA
Plast Reconstr Surg 1997 Nov;100(6):1491-6. doi: 10.1097/00006534-199711000-00018. PMID: 9385961

Diagnosis

Pillai MR, Pabolu C, R R, Chaudhary S, Sr K, Puthuran GV
J AAPOS 2024 Aug;28(4):103950. Epub 2024 Jun 10 doi: 10.1016/j.jaapos.2024.103950. PMID: 38866321
Meyer BI, Williams PJ, Hanif AM, Lenhart PD, Hubbard GB 3rd, Jain N
Retin Cases Brief Rep 2022 Nov 1;16(6):762-765. doi: 10.1097/ICB.0000000000001073. PMID: 33323896
Meester JAN, Sukalo M, Schröder KC, Schanze D, Baynam G, Borck G, Bramswig NC, Duman D, Gilbert-Dussardier B, Holder-Espinasse M, Itin P, Johnson DS, Joss S, Koillinen H, McKenzie F, Morton J, Nelle H, Reardon W, Roll C, Salih MA, Savarirayan R, Scurr I, Splitt M, Thompson E, Titheradge H, Travers CP, Van Maldergem L, Whiteford M, Wieczorek D, Vandeweyer G, Trembath R, Van Laer L, Loeys BL, Zenker M, Southgate L, Wuyts W
Hum Mutat 2018 Sep;39(9):1246-1261. Epub 2018 Jul 4 doi: 10.1002/humu.23567. PMID: 29924900Free PMC Article
Schouten JN, Verheij J, Seijo S
Orphanet J Rare Dis 2015 May 30;10:67. doi: 10.1186/s13023-015-0288-8. PMID: 26025214Free PMC Article
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Am J Med Genet A 2013 Jun;161A(6):1386-9. Epub 2013 Apr 23 doi: 10.1002/ajmg.a.35864. PMID: 23613382

Therapy

Sezgin B, Sibar S, Findikcioglu K, Sencan A, Emmez H, Baykaner K, Ozmen S
J Wound Care 2017 Jun 2;26(6):342-345. doi: 10.12968/jowc.2017.26.6.342. PMID: 28598754
Kalina MA, Kalina-Faska B, Paprocka J, Jamroz E, Pyrkosz A, Marszał E, Małecka-Tendera E
Clin Genet 2010 Sep;78(3):227-35. Epub 2010 May 22 doi: 10.1111/j.1399-0004.2010.01470.x. PMID: 20560985

Prognosis

Lukas ML, Harald G, Sanz J, Trippel M, Sabina G, Jochen R
Am J Med Genet A 2022 Nov;188(11):3318-3323. Epub 2022 Sep 4 doi: 10.1002/ajmg.a.62961. PMID: 36059114Free PMC Article
van Nisselrooij AEL, Herling L, Clur SA, Linskens IH, Pajkrt E, Rammeloo LA, Ten Harkel ADJ, Hazekamp MG, Blom NA, Haak MC
Prenat Diagn 2021 May;41(6):754-765. Epub 2021 Feb 26 doi: 10.1002/pd.5907. PMID: 33480066Free PMC Article
Huang S, Yang L, Zhao L, Xu R, Wu Y
DNA Cell Biol 2020 May;39(5):783-789. Epub 2020 Mar 4 doi: 10.1089/dna.2019.5200. PMID: 32129674
Sukalo M, Tilsen F, Kayserili H, Müller D, Tüysüz B, Ruddy DM, Wakeling E, Ørstavik KH, Snape KM, Trembath R, De Smedt M, van der Aa N, Skalej M, Mundlos S, Wuyts W, Southgate L, Zenker M
Hum Mutat 2015 Jun;36(6):593-8. Epub 2015 Apr 21 doi: 10.1002/humu.22795. PMID: 25824905
Pousti TJ, Bartlett RA
Plast Reconstr Surg 1997 Nov;100(6):1491-6. doi: 10.1097/00006534-199711000-00018. PMID: 9385961

Clinical prediction guides

Perrot A, Rickert-Sperling S
Adv Exp Med Biol 2024;1441:505-534. doi: 10.1007/978-3-031-44087-8_27. PMID: 38884729
Meyer BI, Williams PJ, Hanif AM, Lenhart PD, Hubbard GB 3rd, Jain N
Retin Cases Brief Rep 2022 Nov 1;16(6):762-765. doi: 10.1097/ICB.0000000000001073. PMID: 33323896
Huang S, Yang L, Zhao L, Xu R, Wu Y
DNA Cell Biol 2020 May;39(5):783-789. Epub 2020 Mar 4 doi: 10.1089/dna.2019.5200. PMID: 32129674
Sukalo M, Tilsen F, Kayserili H, Müller D, Tüysüz B, Ruddy DM, Wakeling E, Ørstavik KH, Snape KM, Trembath R, De Smedt M, van der Aa N, Skalej M, Mundlos S, Wuyts W, Southgate L, Zenker M
Hum Mutat 2015 Jun;36(6):593-8. Epub 2015 Apr 21 doi: 10.1002/humu.22795. PMID: 25824905
Verdyck P, Holder-Espinasse M, Hul WV, Wuyts W
Eur J Hum Genet 2003 Jun;11(6):457-63. doi: 10.1038/sj.ejhg.5200980. PMID: 12774039

Recent systematic reviews

van Nisselrooij AEL, Herling L, Clur SA, Linskens IH, Pajkrt E, Rammeloo LA, Ten Harkel ADJ, Hazekamp MG, Blom NA, Haak MC
Prenat Diagn 2021 May;41(6):754-765. Epub 2021 Feb 26 doi: 10.1002/pd.5907. PMID: 33480066Free PMC Article

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