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Atelosteogenesis type II(AO2)

MedGen UID:
338072
Concept ID:
C1850554
Disease or Syndrome
Synonyms: AO2; Atelosteogenesis type 2; Neonatal osseous dysplasia 1; NEONATAL OSSEOUS DYSPLASIA I
SNOMED CT: Atelosteogenesis type 2 (254055004); Atelosteogenesis de la Chapelle type (254055004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SLC26A2 (5q32)
 
Monarch Initiative: MONDO:0009727
OMIM®: 256050
Orphanet: ORPHA56304

Disease characteristics

Excerpted from the GeneReview: SLC26A2-Related Atelosteogenesis
Clinical features of SLC26A2-related atelosteogenesis include rhizomelic limb shortening with normal-sized skull, hitchhiker thumbs, small chest, protuberant abdomen, cleft palate, and distinctive facial features (midface retrusion, depressed nasal bridge, epicanthus, micrognathia). Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. SLC26A2-related atelosteogenesis is usually lethal at birth or shortly thereafter due to pulmonary hypoplasia and tracheobronchomalacia. However, it exists in a continuous phenotypic spectrum with SLC26A2-related diastrophic dysplasia, and long-term survivors have been reported. [from GeneReviews]
Authors:
Andrea Superti-Furga  |  Sheila Unger   view full author information

Additional description

From MedlinePlus Genetics
Atelosteogenesis type 2 is a severe disorder of cartilage and bone development. Infants born with this condition have very short arms and legs, a narrow chest, and a prominent, rounded abdomen. This disorder is also characterized by an opening in the roof of the mouth (a cleft palate), distinctive facial features, an inward- and upward-turning foot (clubfoot), and unusually positioned thumbs (hitchhiker thumbs).

The signs and symptoms of atelosteogenesis type 2 are similar to those of another skeletal disorder called diastrophic dysplasia; however, atelosteogenesis type 2 is typically more severe. As a result of serious health problems, infants with this disorder are usually stillborn or die soon after birth from respiratory failure. Some infants, however, have lived for a short time with intensive medical support.  https://medlineplus.gov/genetics/condition/atelosteogenesis-type-2

Clinical features

From HPO
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Micromelia
MedGen UID:
10031
Concept ID:
C0025995
Congenital Abnormality
The presence of abnormally small extremities.
Limb undergrowth
MedGen UID:
116086
Concept ID:
C0239399
Finding
Limb shortening because of underdevelopment of one or more bones of the extremities.
Hitchhiker thumb
MedGen UID:
609206
Concept ID:
C0431887
Congenital Abnormality
With the hand relaxed and the thumb in the plane of the palm, the axis of the thumb forms an angle of at least 90 degrees with the long axis of the hand.
Flat acetabular roof
MedGen UID:
373340
Concept ID:
C1837485
Finding
Flattening of the superior part of the acetabulum, which is a cup-shaped cavity at the base of the hipbone into which the ball-shaped head of the femur fits. The acetabular roof thereby appears horizontal rather than arched, as it normally does.
Sandal gap
MedGen UID:
374376
Concept ID:
C1840069
Finding
A widely spaced gap between the first toe (the great toe) and the second toe.
Short middle phalanx of finger
MedGen UID:
337690
Concept ID:
C1846950
Finding
Short (hypoplastic) middle phalanx of finger, affecting one or more fingers.
Dumbbell-shaped femur
MedGen UID:
870603
Concept ID:
C4025052
Anatomical Abnormality
The femur is shortened and displays flaring (widening) of the metaphyses.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Cervical kyphosis
MedGen UID:
107898
Concept ID:
C0575170
Finding
Exaggerated convexity of the cervical vertebral column, causing the cervical spine to bow outwards and take on a rounded appearance.
Lumbar hyperlordosis
MedGen UID:
263149
Concept ID:
C1184923
Finding
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Coronal cleft vertebrae
MedGen UID:
320483
Concept ID:
C1834954
Finding
Frontal schisis (cleft or cleavage) of vertebral bodies.
Thoracic hypoplasia
MedGen UID:
373339
Concept ID:
C1837482
Congenital Abnormality
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Horizontal sacrum
MedGen UID:
342531
Concept ID:
C1850558
Finding
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Short greater sciatic notch
MedGen UID:
401058
Concept ID:
C1866689
Finding
The sacroiliac joint in the bony pelvis connects the sacrum and the ilium of the pelvis, which are joined by strong ligaments. The notch is located directly superior to the joint. This term refers to a reduction in the height of the notch.
Abnormal pelvic girdle bone morphology
MedGen UID:
866545
Concept ID:
C4020847
Anatomical Abnormality
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Increased intervertebral space
MedGen UID:
868122
Concept ID:
C4022513
Finding
An increase in the vertical distance between adjacent vertebral bodies, observed as an increase in the intervertebral disc space.
Bifid humerus
MedGen UID:
871080
Concept ID:
C4025545
Anatomical Abnormality
Clefting affecting the humerus.
Lacunar halos around chondrocytes
MedGen UID:
1710079
Concept ID:
C5397935
Finding
Concentric rings around the chondrocytes.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
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.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Biji IK, Yadav S, Kulshrestha S, Saxena R, Kohli S, Verma IC, Kumar B, Puri RD
Eur J Med Genet 2022 Oct;65(10):104595. Epub 2022 Aug 22 doi: 10.1016/j.ejmg.2022.104595. PMID: 36007841
Dwyer E, Hyland J, Modaff P, Pauli RM
Am J Med Genet A 2010 Dec;152A(12):3043-50. doi: 10.1002/ajmg.a.33736. PMID: 21077202

Recent clinical studies

Etiology

Wessels A, Wainwright HC, Beighton P
Pediatr Dev Pathol 2011 Nov-Dec;14(6):496-500. Epub 2011 Oct 10 doi: 10.2350/11-01-0969-CR.1. PMID: 21985323
Miyake A, Nishimura G, Futami T, Ohashi H, Chiba K, Toyama Y, Furuichi T, Ikegawa S
J Hum Genet 2008;53(8):764-768. Epub 2008 Jun 14 doi: 10.1007/s10038-008-0305-z. PMID: 18553123
Macías-Gómez NM, Mégarbané A, Leal-Ugarte E, Rodríguez-Rojas LX, Barros-Núñez P
Am J Med Genet A 2004 Aug 30;129A(2):190-2. doi: 10.1002/ajmg.a.30149. PMID: 15316973
Brodie SG, Lachman RS, Crandall BF, Fox MA, Rimoin DL, Cohn DH, Wilcox WR
Am J Med Genet 1998 Nov 16;80(3):247-51. PMID: 9843047
Sillence D, Worthington S, Dixon J, Osborn R, Kozlowski K
Pediatr Radiol 1997 May;27(5):388-96. doi: 10.1007/s002470050154. PMID: 9133349

Diagnosis

Biji IK, Yadav S, Kulshrestha S, Saxena R, Kohli S, Verma IC, Kumar B, Puri RD
Eur J Med Genet 2022 Oct;65(10):104595. Epub 2022 Aug 22 doi: 10.1016/j.ejmg.2022.104595. PMID: 36007841
Wessels A, Wainwright HC, Beighton P
Pediatr Dev Pathol 2011 Nov-Dec;14(6):496-500. Epub 2011 Oct 10 doi: 10.2350/11-01-0969-CR.1. PMID: 21985323
Miller E, Blaser S, Miller S, Keating S, Thompson M, Unger S, Toi A, Berger H, Chong K
Pediatr Radiol 2008 Dec;38(12):1345-9. Epub 2008 Aug 21 doi: 10.1007/s00247-008-0974-y. PMID: 18716767
Schrander-Stumpel C, Havenith M, Linden EV, Maertzdorf W, Offermans J, van der Harten J
Clin Dysmorphol 1994 Oct;3(4):318-27. PMID: 7632220
Nores JA, Rotmensch S, Romero R, Avila C, Inati M, Hobbins JC
Prenat Diagn 1992 Sep;12(9):741-53. doi: 10.1002/pd.1970120907. PMID: 1279661

Prognosis

Biji IK, Yadav S, Kulshrestha S, Saxena R, Kohli S, Verma IC, Kumar B, Puri RD
Eur J Med Genet 2022 Oct;65(10):104595. Epub 2022 Aug 22 doi: 10.1016/j.ejmg.2022.104595. PMID: 36007841
Wessels A, Wainwright HC, Beighton P
Pediatr Dev Pathol 2011 Nov-Dec;14(6):496-500. Epub 2011 Oct 10 doi: 10.2350/11-01-0969-CR.1. PMID: 21985323
Dwyer E, Hyland J, Modaff P, Pauli RM
Am J Med Genet A 2010 Dec;152A(12):3043-50. doi: 10.1002/ajmg.a.33736. PMID: 21077202
Hästbacka J, Superti-Furga A, Wilcox WR, Rimoin DL, Cohn DH, Lander ES
Am J Hum Genet 1996 Feb;58(2):255-62. PMID: 8571951Free PMC Article
Schrander-Stumpel C, Havenith M, Linden EV, Maertzdorf W, Offermans J, van der Harten J
Clin Dysmorphol 1994 Oct;3(4):318-27. PMID: 7632220

Clinical prediction guides

Biji IK, Yadav S, Kulshrestha S, Saxena R, Kohli S, Verma IC, Kumar B, Puri RD
Eur J Med Genet 2022 Oct;65(10):104595. Epub 2022 Aug 22 doi: 10.1016/j.ejmg.2022.104595. PMID: 36007841
Wessels A, Wainwright HC, Beighton P
Pediatr Dev Pathol 2011 Nov-Dec;14(6):496-500. Epub 2011 Oct 10 doi: 10.2350/11-01-0969-CR.1. PMID: 21985323
Dwyer E, Hyland J, Modaff P, Pauli RM
Am J Med Genet A 2010 Dec;152A(12):3043-50. doi: 10.1002/ajmg.a.33736. PMID: 21077202
Macías-Gómez NM, Mégarbané A, Leal-Ugarte E, Rodríguez-Rojas LX, Barros-Núñez P
Am J Med Genet A 2004 Aug 30;129A(2):190-2. doi: 10.1002/ajmg.a.30149. PMID: 15316973
Sillence D, Worthington S, Dixon J, Osborn R, Kozlowski K
Pediatr Radiol 1997 May;27(5):388-96. doi: 10.1007/s002470050154. PMID: 9133349

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