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Adams-Oliver syndrome 2(AOS2)

MedGen UID:
481812
Concept ID:
C3280182
Disease or Syndrome
Synonym: AOS2
 
Gene (location): DOCK6 (19p13.2)
 
Monarch Initiative: MONDO:0013635
OMIM®: 614219

Authors:
Anna Lehman  |  Wim Wuyts  |  Millan S Patel   view full author information

Additional descriptions

From OMIM
Adams-Oliver syndrome-2 (AOS2) is an autosomal recessive multiple congenital anomaly syndrome characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects, in association with variable involvement of the brain, eyes, and cardiovascular systems (summary by Shaheen et al., 2011). For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (100300).  http://www.omim.org/entry/614219
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
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Short middle phalanx of finger
MedGen UID:
337690
Concept ID:
C1846950
Finding
Short (hypoplastic) middle phalanx of finger, affecting one or more fingers.
Absent distal phalanges
MedGen UID:
396111
Concept ID:
C1861339
Finding
Aplasia (absence) of the distal phalanges.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Polymicrogyria
MedGen UID:
78605
Concept ID:
C0266464
Congenital Abnormality
Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Retrocerebellar cyst
MedGen UID:
335172
Concept ID:
C1845370
Finding
Lateral ventricle dilatation
MedGen UID:
383904
Concept ID:
C1856409
Pathologic Function
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Low anterior hairline
MedGen UID:
331280
Concept ID:
C1842366
Finding
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella.
Narrow palpebral fissure
MedGen UID:
382506
Concept ID:
C2675021
Finding
Reduction in the vertical distance between the upper and lower eyelids.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
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.
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
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.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
Developmental cataract
MedGen UID:
3202
Concept ID:
C0009691
Congenital Abnormality
A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

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
Dugan SL, Botto LD, Hedlund GL, Bale JF Jr
Semin Pediatr Neurol 2018 Jul;26:135-139. Epub 2017 Apr 2 doi: 10.1016/j.spen.2017.03.022. PMID: 29961505
Aarabi M, Sniezek O, Jiang H, Saller DN, Bellissimo D, Yatsenko SA, Rajkovic A
Hum Genet 2018 Feb;137(2):175-181. Epub 2018 Feb 1 doi: 10.1007/s00439-017-1860-1. PMID: 29392406
Southgate L, Sukalo M, Karountzos ASV, Taylor EJ, Collinson CS, Ruddy D, Snape KM, Dallapiccola B, Tolmie JL, Joss S, Brancati F, Digilio MC, Graul-Neumann LM, Salviati L, Coerdt W, Jacquemin E, Wuyts W, Zenker M, Machado RD, Trembath RC
Circ Cardiovasc Genet 2015 Aug;8(4):572-581. Epub 2015 May 11 doi: 10.1161/CIRCGENETICS.115.001086. PMID: 25963545Free PMC Article
Piazza AJ, Blackston D, Sola A
Am J Med Genet A 2004 Oct 1;130A(2):172-5. doi: 10.1002/ajmg.a.30210. PMID: 15372524

Diagnosis

Alzahem T, Alsalamah AK, Mura M, Alsulaiman SM
Ophthalmic Genet 2020 Aug;41(4):377-380. Epub 2020 Jun 5 doi: 10.1080/13816810.2020.1776339. PMID: 32498638
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
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
Garzon MC, Schweiger E
Semin Cutan Med Surg 2004 Jun;23(2):99-106. doi: 10.1016/j.sder.2004.01.003. PMID: 15295919

Therapy

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

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
Kyriakou G, Gialeli E, Vryzaki E, Georgiou S
Acta Dermatovenerol Croat 2020 Dec;28(4):247-248. PMID: 33835001
Alzahem T, Alsalamah AK, Mura M, Alsulaiman SM
Ophthalmic Genet 2020 Aug;41(4):377-380. Epub 2020 Jun 5 doi: 10.1080/13816810.2020.1776339. PMID: 32498638
Dugan SL, Botto LD, Hedlund GL, Bale JF Jr
Semin Pediatr Neurol 2018 Jul;26:135-139. Epub 2017 Apr 2 doi: 10.1016/j.spen.2017.03.022. PMID: 29961505
Cohen I, Silberstein E, Perez Y, Landau D, Elbedour K, Langer Y, Kadir R, Volodarsky M, Sivan S, Narkis G, Birk OS
Eur J Hum Genet 2014 Mar;22(3):374-8. Epub 2013 Jul 17 doi: 10.1038/ejhg.2013.159. PMID: 23860037Free PMC Article

Clinical prediction guides

Kyriakou G, Gialeli E, Vryzaki E, Georgiou S
Acta Dermatovenerol Croat 2020 Dec;28(4):247-248. PMID: 33835001
Schröder KC, Duman D, Tekin M, Schanze D, Sukalo M, Meester J, Wuyts W, Zenker M
Am J Med Genet A 2019 Nov;179(11):2246-2251. Epub 2019 Jul 31 doi: 10.1002/ajmg.a.61313. PMID: 31368252
Southgate L, Sukalo M, Karountzos ASV, Taylor EJ, Collinson CS, Ruddy D, Snape KM, Dallapiccola B, Tolmie JL, Joss S, Brancati F, Digilio MC, Graul-Neumann LM, Salviati L, Coerdt W, Jacquemin E, Wuyts W, Zenker M, Machado RD, Trembath RC
Circ Cardiovasc Genet 2015 Aug;8(4):572-581. Epub 2015 May 11 doi: 10.1161/CIRCGENETICS.115.001086. PMID: 25963545Free PMC Article
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
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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