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Adams-Oliver syndrome 5(AOS5)

MedGen UID:
863407
Concept ID:
C4014970
Disease or Syndrome
Synonym: AOS5
 
Gene (location): NOTCH1 (9q34.3)
 
Monarch Initiative: MONDO:0014459
OMIM®: 616028

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 (AOS) 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 recurrently seen. 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/616028
From MedlinePlus Genetics
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.

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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/adams-oliver-syndrome

Clinical features

From HPO
Cavernous hemangioma
MedGen UID:
9184
Concept ID:
C0018920
Neoplastic Process
The presence of a cavernous hemangioma. A hemangioma characterized by large endothelial spaces (caverns) is called a cavernous hemangioma.
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.
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
Right ventricular hypertrophy
MedGen UID:
57981
Concept ID:
C0162770
Disease or Syndrome
In this case the right ventricle is more muscular than normal, causing a characteristic boot-shaped (coeur-en-sabot) appearance as seen on anterior- posterior chest x-rays. Right ventricular hypertrophy is commonly associated with any form of right ventricular outflow obstruction or pulmonary hypertension, which may in turn owe its origin to left-sided disease. The echocardiographic signs are thickening of the anterior right ventricular wall and the septum. Cavity size is usually normal, or slightly enlarged. In many cases there is associated volume overload present due to tricuspid regurgitation, in the absence of this, septal motion is normal.
Right atrial enlargement
MedGen UID:
677114
Concept ID:
C0748427
Disease or Syndrome
Increase in size of the right atrium.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Esophageal varix
MedGen UID:
5027
Concept ID:
C0014867
Disease or Syndrome
Extreme dilation of the submucusoal veins in the lower portion of the esophagus.
Portal vein thrombosis
MedGen UID:
56372
Concept ID:
C0155773
Disease or Syndrome
Thrombosis of the portal vein and/or its tributaries, which include the splenic vein and the superior and inferior mesenteric veins.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Hypersplenism
MedGen UID:
9372
Concept ID:
C0020532
Disease or Syndrome
A malfunctioning of the spleen in which it prematurely destroys red blood cells.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Aplasia cutis congenita
MedGen UID:
79390
Concept ID:
C0282160
Congenital Abnormality
Aplasia cutis congenita (ACC) is defined as congenital localized absence of skin. The skin appears as a thin, transparent membrane through which the underlying structures are visible. The location is usually on the scalp (Evers et al., 1995). Approximately 20 to 30% of cases have underlying osseous involvement (Elliott and Teebi, 1997). Autosomal dominant inheritance is most common, but recessive inheritance has also been reported. Cutaneous aplasia of the scalp vertex also occurs in Johanson-Blizzard syndrome (243800) and Adams-Oliver syndrome (AOS; 100300). A defect in the scalp is sometimes found in cases of trisomy 13 and in about 15% of cases of deletion of the short arm of chromosome 4, the Wolf-Hirschhorn syndrome (WHS; 194190) (Hirschhorn et al., 1965; Fryns et al., 1973). Evers et al. (1995) provided a list of disorders associated with aplasia cutis congenita, classified according to etiology. They also tabulated points of particular significance in history taking and examination of patients with ACC.
Congenital livedo reticularis
MedGen UID:
83381
Concept ID:
C0345419
Congenital Abnormality
Isolated and classic cutis marmorata telangiectatica congenita (CMTC) are characterized by congenital skin changes including erythematous-to-violaceous, reticulated, net-like or marbled-appearing patches of skin that do not mostly or completely resolve with warming or any other acute intervention. Individuals with isolated CMTC have no other syndromic features, and skin lesions tend to fade or resolve. Those with classic CMTC may have accompanying hemihypoplasia with body asymmetry, skin atrophy or ulceration, other vascular malformations, and occasional ocular issues (early-onset glaucoma and/or peripheral retinal vascular attenuation) but do not have other malformations, dysmorphic features, or cognitive impairment. The most common location for the CMTC lesions is on the legs. An affected limb may also display weakness or be unusually susceptible to cold compared to an unaffected limb. In more than half of affected individuals, skin lesions will generally fade across a wide range in age (6 weeks to 26 years), most commonly in the first year of life, but may not resolve completely.
Dystrophic toenail
MedGen UID:
318813
Concept ID:
C1833225
Finding
Toenail changes apart from changes of the color of the toenail (nail dyschromia) that involve partial or complete disruption of the various keratinous layers of the nail plate.
Hypoplastic toenails
MedGen UID:
332409
Concept ID:
C1837279
Finding
Underdevelopment of the toenail.
Absent toenail
MedGen UID:
336719
Concept ID:
C1844555
Congenital Abnormality
Congenital absence of the toenail.

Recent clinical studies

Etiology

Stanley KJ, Kalbfleisch KJ, Moran OM, Chaturvedi RR, Roifman M, Chen X, Manshaei R, Martin N, McDermott S, McNiven V, Myles-Reid D, Nield LE, Reuter MS, Schwartz MLB, Shannon P, Silver R, Somerville C, Teitelbaum R, Zahavich L, Bassett AS, Kim RH, Mital S, Chitayat D, Jobling RK
Eur J Hum Genet 2024 Jul;32(7):795-803. Epub 2024 May 22 doi: 10.1038/s41431-024-01629-4. PMID: 38778082Free PMC Article
Helman G, Zarekiani P, Tromp SAM, Andrews A, Botto LD, Bonkowsky JL, Chassevent A, Giorgio E, Pippucci T, Wei S, Smith-Hicks C, Vaula G, Willemsen MAAP, Schimmel M, Vollert K, Shimizu F, Kanda T, Lynch M, Roscioli T, Taft RJ, Simons C, Bugiani M, Kuijpers TW, van der Knaap MS
Ann Neurol 2022 Nov;92(5):895-901. Epub 2022 Aug 20 doi: 10.1002/ana.26477. PMID: 35947102
Dedania VS, Moinuddin O, Lagrou LM, Sathrasala S, Cord Medina FM, Del Monte MA, Chang EY, Bohnsack BL, Besirli CG
Ophthalmol Retina 2019 Sep;3(9):791-801. Epub 2019 May 1 doi: 10.1016/j.oret.2019.03.025. PMID: 31147303
Mesrati H, Amouri M, Chaaben H, Masmoudi A, Boudaya S, Turki H
Int J Dermatol 2015 Dec;54(12):1370-5. Epub 2015 May 27 doi: 10.1111/ijd.12707. PMID: 26016611
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
Saudi Med J 2006 Mar;27 Suppl 1:S69-80. PMID: 16532134

Diagnosis

Stanley KJ, Kalbfleisch KJ, Moran OM, Chaturvedi RR, Roifman M, Chen X, Manshaei R, Martin N, McDermott S, McNiven V, Myles-Reid D, Nield LE, Reuter MS, Schwartz MLB, Shannon P, Silver R, Somerville C, Teitelbaum R, Zahavich L, Bassett AS, Kim RH, Mital S, Chitayat D, Jobling RK
Eur J Hum Genet 2024 Jul;32(7):795-803. Epub 2024 May 22 doi: 10.1038/s41431-024-01629-4. PMID: 38778082Free PMC Article
Dedania VS, Moinuddin O, Lagrou LM, Sathrasala S, Cord Medina FM, Del Monte MA, Chang EY, Bohnsack BL, Besirli CG
Ophthalmol Retina 2019 Sep;3(9):791-801. Epub 2019 May 1 doi: 10.1016/j.oret.2019.03.025. PMID: 31147303
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
Mesrati H, Amouri M, Chaaben H, Masmoudi A, Boudaya S, Turki H
Int J Dermatol 2015 Dec;54(12):1370-5. Epub 2015 May 27 doi: 10.1111/ijd.12707. PMID: 26016611
Becker R, Kunze J, Horn D, Gasiorek-Wiens A, Entezami M, Rossi R, Guschmann M, Sarioglu N
Ultrasound Obstet Gynecol 2002 Nov;20(5):506-10. doi: 10.1046/j.1469-0705.2002.00839.x. PMID: 12423491

Prognosis

Santaniello C, Faversani A, Corsaro L, Melloni G, Motta S, Mandorino E, Sacco D, Stioui S, Ferrara F, Barteselli D, De Vita D, Manuelli D, Costantino L
Genes (Basel) 2024 Apr 24;15(5) doi: 10.3390/genes15050536. PMID: 38790165Free 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
Shamseldin HE, Anazi S, Wakil SM, Faqeih E, El Khashab HY, Salih MA, Al-Qattan MM, Hashem M, Alsedairy H, Alkuraya FS
Am J Med Genet A 2016 May;170A(5):1245-50. Epub 2016 Jan 8 doi: 10.1002/ajmg.a.37550. PMID: 26749485

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
Santaniello C, Faversani A, Corsaro L, Melloni G, Motta S, Mandorino E, Sacco D, Stioui S, Ferrara F, Barteselli D, De Vita D, Manuelli D, Costantino L
Genes (Basel) 2024 Apr 24;15(5) doi: 10.3390/genes15050536. PMID: 38790165Free PMC Article
De Zoysa P, Toubat O, Harvey D, Choi J, Kumar SR
Stem Cells Dev 2021 Jun 15;30(12):611-621. Epub 2021 May 31 doi: 10.1089/scd.2021.0058. PMID: 33899511Free PMC Article
Shamseldin HE, Anazi S, Wakil SM, Faqeih E, El Khashab HY, Salih MA, Al-Qattan MM, Hashem M, Alsedairy H, Alkuraya FS
Am J Med Genet A 2016 May;170A(5):1245-50. Epub 2016 Jan 8 doi: 10.1002/ajmg.a.37550. PMID: 26749485
Stittrich AB, Lehman A, Bodian DL, Ashworth J, Zong Z, Li H, Lam P, Khromykh A, Iyer RK, Vockley JG, Baveja R, Silva ES, Dixon J, Leon EL, Solomon BD, Glusman G, Niederhuber JE, Roach JC, Patel MS
Am J Hum Genet 2014 Sep 4;95(3):275-84. Epub 2014 Aug 14 doi: 10.1016/j.ajhg.2014.07.011. PMID: 25132448Free PMC Article

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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