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Achondrogenesis, type IA(ACG1A)

MedGen UID:
78546
Concept ID:
C0265273
Congenital Abnormality
Synonyms: ACG1A; Achondrogenesis Houston-Harris type; Achondrogenesis type 1A
SNOMED CT: Achondrogenesis, type IA (42725006)
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): TRIP11 (14q32.12)
 
Monarch Initiative: MONDO:0008701
OMIM®: 200600
Orphanet: ORPHA93299

Definition

The term achondrogenesis has been used to characterize the most severe forms of chondrodysplasia in humans, invariably lethal before or shortly after birth. Achondrogenesis type I is a severe chondrodystrophy characterized radiographically by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death (Maroteaux and Lamy, 1968; Langer et al., 1969). In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues. Classification of Achondrogenesis Achondrogenesis was traditionally divided into 2 types: type I (Parenti-Fraccaro) and type II (Langer-Saldino). Borochowitz et al. (1988) suggested that achondrogenesis type I of Parenti-Fraccaro should be classified into 2 distinct disorders: type IA, corresponding to the cases originally published by Houston et al. (1972) and Harris et al. (1972), and type IB (600972), corresponding to the case originally published by Fraccaro (1952). Analysis of the case reported by Parenti (1936) by Borochowitz et al. (1988) suggested the diagnosis of achondrogenesis type II, i.e., the Langer-Saldino type (200610). Type IA would be classified as lethal achondrogenesis, Houston-Harris type; type IB, lethal achondrogenesis, Fraccaro type; and type II, lethal achondrogenesis-hypochondrogenesis, Langer-Saldino type. Superti-Furga (1996) suggested that hypochondrogenesis should be considered separately from achondrogenesis type II because the phenotype can be much milder. Genetic Heterogeneity of Achondrogenesis Achondrogenesis type IB (ACG1B; 600972) is caused by mutation in the DTDST gene (606718), and achondrogenesis type II (ACG2; 200610) is caused by mutation in the COL2A1 gene (120140). [from OMIM]

Additional description

From MedlinePlus Genetics
Achondrogenesis type 1B, also known as the Parenti-Fraccaro type, is characterized by extremely short limbs, a narrow chest, and a prominent, rounded abdomen. The fingers and toes are short and the feet may turn inward and upward (clubfeet). Affected infants frequently have a soft out-pouching around the belly-button (an umbilical hernia) or near the groin (an inguinal hernia).

Achondrogenesis type 1A, which is also called the Houston-Harris type, is the least well understood of the three forms. Affected infants have extremely short limbs, a narrow chest, short ribs that fracture easily, and a lack of normal bone formation (ossification) in the skull, spine, and pelvis.

Infants with achondrogenesis type 2, which is sometimes called the Langer-Saldino type, have short arms and legs, a narrow chest with short ribs, and underdeveloped lungs. This condition is also associated with a lack of ossification in the spine and pelvis. Distinctive facial features include a prominent forehead, a small chin, and, in some cases, an opening in the roof of the mouth (a cleft palate). The abdomen is enlarged, and affected infants often have a condition called hydrops fetalis, in which excess fluid builds up in the body before birth.

Researchers have described at least three forms of achondrogenesis, designated as type 1A, type 1B, and type 2. The types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. However, types 1A and 1B are often hard to tell apart without genetic testing.

Achondrogenesis is a group of severe disorders that affect cartilage and bone development. These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of serious health problems, infants with achondrogenesis usually die before birth, are stillborn, or die soon after birth from respiratory failure. However, some infants have lived for a short time with intensive medical support.  https://medlineplus.gov/genetics/condition/achondrogenesis

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.
Hypoplasia of the radius
MedGen UID:
672334
Concept ID:
C0685381
Congenital Abnormality
Underdevelopment of the radius.
Severe limb shortening
MedGen UID:
331977
Concept ID:
C1835446
Finding
Abnormal hand bone ossification
MedGen UID:
866888
Concept ID:
C4021244
Finding
An abnormality of the formation and mineralization of any bone of the skeleton of hand.
Abnormal femoral metaphysis morphology
MedGen UID:
870591
Concept ID:
C4025040
Anatomical Abnormality
An anomaly of the femoral metaphysis.
Protuberant abdomen
MedGen UID:
340750
Concept ID:
C1854928
Finding
A thrusting or bulging out of the abdomen.
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.
Barrel-shaped chest
MedGen UID:
120497
Concept ID:
C0264172
Finding
A rounded, bulging chest that resembles the shape of a barrel. That is, there is an increased anteroposterior diameter and usually some degree of kyphosis.
Multiple rib fractures
MedGen UID:
75784
Concept ID:
C0272567
Injury or Poisoning
More than one fracture of the ribs. Callus formation around multiple rib fractures can produce a row of multiple rounded expansions (beadlike prominences) giving the appearance of beaded ribs. Note that rachitic rosary would have one bead per rib (a swelling at the costochondral junction), while beaded ribs in the context of multiple rib fractures have multiple beads (fractures) along the same rib.
Short thorax
MedGen UID:
140876
Concept ID:
C0426789
Finding
Reduced inferior to superior extent of the thorax.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Short clavicles
MedGen UID:
96529
Concept ID:
C0426799
Congenital Abnormality
Reduced length of the clavicles.
Broad clavicles
MedGen UID:
98091
Concept ID:
C0426801
Finding
Increased width (cross-sectional diameter) of the clavicles.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
Bowing of the arm
MedGen UID:
488899
Concept ID:
C0426863
Finding
A bending or abnormal curvature affecting a long bone of the arm.
Decreased skull ossification
MedGen UID:
609330
Concept ID:
C0432073
Congenital Abnormality
A reduction in the magnitude or amount of ossification of the skull.
Hypoplastic scapulae
MedGen UID:
337579
Concept ID:
C1846434
Finding
Underdeveloped scapula.
Disproportionate short-trunk short stature
MedGen UID:
337580
Concept ID:
C1846435
Finding
A type of disproportionate short stature characterized by a short trunk but a average-sized limbs.
Flaring of rib cage
MedGen UID:
381496
Concept ID:
C1854780
Finding
The presence of wide, concave anterior rib ends.
Hypoplastic ischia
MedGen UID:
347146
Concept ID:
C1859447
Finding
Underdevelopment of the ischium, which forms the lower and back part of the hip bone.
Unossified vertebral bodies
MedGen UID:
349749
Concept ID:
C1860202
Finding
A lack of ossification of the vertebral bodies.
Bell-shaped thorax
MedGen UID:
351320
Concept ID:
C1865186
Finding
The rib cage has the shape of a wide mouthed bell. That is, the superior portion of the rib cage is constricted, followed by a convex region, and the inferior portion of the rib cage expands again to have a large diameter.
Hypoplastic sacrum
MedGen UID:
370356
Concept ID:
C1970816
Finding
Abnormal foot bone ossification
MedGen UID:
892416
Concept ID:
C4021241
Anatomical Abnormality
An abnormality of the formation and mineralization of any bone of the skeleton of foot.
Turricephaly
MedGen UID:
1726910
Concept ID:
C5399823
Congenital Abnormality
Tall head relative to width and length.
Bowing of the legs
MedGen UID:
1807399
Concept ID:
C5574706
Finding
A bending or abnormal curvature affecting a long bone of the leg.
Crescent-shaped iliac bone
MedGen UID:
1054883
Concept ID:
CN377485
Finding
Deficient mineralization of the iliac wings, giving a paraglider/crescent shape to the iliac bone.
Abnormal ischium ossification
MedGen UID:
1053907
Concept ID:
CN377486
Finding
An abnormality of the formation and mineralization of ischial bones.
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.
Protruding tongue
MedGen UID:
66831
Concept ID:
C0241442
Finding
Tongue extending beyond the alveolar ridges or teeth at rest.
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.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Flat face
MedGen UID:
342829
Concept ID:
C1853241
Finding
Absence of concavity or convexity of the face when viewed in profile.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Hypoplastic nasal bridge
MedGen UID:
356319
Concept ID:
C1865597
Finding
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Hydrops fetalis
MedGen UID:
6947
Concept ID:
C0020305
Disease or Syndrome
The abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema.
Absence of stomach bubble on fetal sonography
MedGen UID:
869203
Concept ID:
C4023625
Finding
By the 14th week of gestation it is nearly always possible to visualized the fluid-filled fetal stomach bubble on prenatal sonography. This term refers to the absence of a normal fetal stomach bubble on fetal ultrasonography performed at around 16 to 20 weeks' gestation.
Increased nuchal translucency
MedGen UID:
869253
Concept ID:
C4023676
Finding
Nuchal translucency is the sonographic appearance of subcutaneous accumulation of liquid in the back of the fetal neck in the first trimester of pregnancy (11-14 gestational weeks of pregnancy).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAchondrogenesis, type IA

Recent clinical studies

Diagnosis

Qian Y, Hu G, Chen M, Liu B, Yan K, Zhou C, Yu Y, Dong M
Am J Med Genet A 2021 Aug;185(8):2482-2487. Epub 2021 May 20 doi: 10.1002/ajmg.a.62260. PMID: 34014608
Vandevijver N, De Die-Smulders CE, Offermans JP, Van Der Linden ES, Arends JW, Sastrowijoto SH, Moerman P, Fryns JP
Genet Couns 1998;9(3):205-9. PMID: 9777343

Prognosis

Vandevijver N, De Die-Smulders CE, Offermans JP, Van Der Linden ES, Arends JW, Sastrowijoto SH, Moerman P, Fryns JP
Genet Couns 1998;9(3):205-9. PMID: 9777343

Clinical prediction guides

Ramírez-García SA, García-Cruz D, Cervantes-Aragón I, Bitar-Alatorre WE, Dávalos-Rodríguez IP, Dávalos-Rodríguez NO, Corona-Rivera JR, Sánchez-Corona J
Cir Cir 2019;86(1):81-89. doi: 10.24875/CIRUE.M18000013. PMID: 30951048

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