Database: OMIMEntry: 108720
LinkDB: 108720
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MIM Entry: 108720
Title:
#108720 ATELOSTEOGENESIS, TYPE I; AOI
;;GIANT CELL CHONDRODYSPLASIA;;
SPONDYLOHUMEROFEMORAL HYPOPLASIA
Text:
A number sign (#) is used with this entry because atelosteogenesis type
I is caused by mutations in the gene encoding filamin B (FLNB; 603381).
CLINICAL FEATURES
Atelosteogenesis is the name given by Maroteaux et al. (1982) to a
lethal chondrodysplasia characterized by distal hypoplasia of the humeri
and femurs, hypoplasia of the mid-thoracic spine, occasionally complete
lack of ossification of single hand bones, and the finding in cartilage
of multiple degenerated chondrocytes which are encapsulated in fibrous
tissue. Rimoin et al. (1980) termed it 'giant cell chondrodysplasia.'
Sillence et al. (1982) reported 2 sporadic cases. The fibulae were
absent. Only the distal phalanges of the hands were ossified. They
termed the disorder 'spondylohumerofemoral hypoplasia.' Hypocellular
areas of growth plate cartilage contained occasional multinuclear giant
cells. The genetics is unclear. Maroteaux et al. (1982) pointed to a
case reported by Kozlowski et al. (1981). Clubfoot and elbow or knee
subluxation may be present. Cleft palate has been observed. The patients
are stillborn or die very early of respiratory distress.
Yang et al. (1983) reported an infant in whom the findings were
consistent with atelosteogenesis. A second case also with giant
chondrocytes on histologic examination of bone, severe laryngeal
stenosis and lethal outcome appeared to have some other skeletal
dysplasia, an as yet unclassified form of spondyloepiphyseal dysplasia.
Yang et al. (1983) concluded, and Sillence and Kozlowski (1983) agreed
on the basis of further observations, that giant chondrocytes are not
specific to one lethal skeletal dysplasia.
According to Whitley et al. (1986), the possible case of de la Chapelle
dysplasia (256050) reported by Salonen (1982) has been reclassified as
atelosteogenesis type I.
Temple et al. (1990) reviewed 10 reported cases, all of which had been
sporadic, and reported an eleventh case, that in an infant with
first-cousin Bengali parents. Polyhydramnios had been a complication of
pregnancy. Multiple joint dislocations and radiological features, of
which the most characteristic were short, distally tapering humeri,
absent or hypoplastic fibulae, deficient vertebral ossification with
coronal clefting, and anarchic ossification of phalanges, were
described.
The disorder that has been called atelosteogenesis type II (Sillence et
al., 1987) may be the same as de la Chapelle dysplasia (256050). Stern
et al. (1990) recommended discarding the term atelosteogenesis type II,
but proposed the term atelosteogenesis III for a distinct condition
(AOIII; 108721).
Hunter and Carpenter (1991) reported a case of atelosteogenesis type I.
They concluded that boomerang dysplasia (112310) and AOI are 'part of a
spectrum, probably reflecting a common etiology.' In a male fetus with a
lethal chondrodysplasia, Greally et al. (1993) documented clinical and
radiologic overlap between AOI and boomerang dysplasia. From histologic
examination, they suggested a defect of cartilage and bone formation as
the basic abnormality.
MOLECULAR GENETICS
In 3 unrelated individuals with sporadically occurring AOI, Krakow et
al. (2004) found heterozygosity for point mutations in FLNB (603381)
that predicted single-residue substitutions in the N-terminal
actin-binding domain of filamin B. They also found 1 individual with
AOIII (108721) who was heterozygous for the same point mutation, 604A-G
(603381.0007), that had been identified in an individual with AOI.
See Also:
Maroteaux et al. (1982); Stevenson and Wilkes (1983)
References:
1. Greally, M. T.; Jewett, T.; Smith, W. L., Jr.; Penick, G. D.; Williamson,
R. A.: Lethal bone dysplasia in a fetus with manifestations of atelosteogenesis
I and boomerang dysplasia. Am. J. Med. Genet. 47: 1086-1091, 1993.
2. Hunter, A. G. W.; Carpenter, B. F.: Atelosteogenesis I and boomerang
dysplasia: a question of nosology. Clin. Genet. 39: 471-480, 1991.
3. Kozlowski, K.; Tsuruta, T.; Kameda, Y.; Kan, A.; Leslie, G.: New
forms of neonatal death dwarfism: report of 3 cases. Pediat. Radiol. 10:
155-160, 1981.
4. Krakow, D.; Robertson, S. P.; King, L. M.; Morgan, T.; Sebald,
E. T.; Bertolotto, C.; Wachsmann-Hogiu, S.; Acuna, D.; Shapiro, S.
S.; Takafuta, T.; Aftimos, S.; Kim, C. A.; and 13 others: Mutations
in the gene encoding filamin B disrupt vertebral segmentation, joint
formation and skeletogenesis. Nature Genet. 36: 405-410, 2004.
5. Maroteaux, P.; Spranger, J.; Stanescu, V.; Le Marec, B.; Pfeiffer,
R. A.; Beighton, P.; Mattei, J. F.: Atelosteogenesis. Am. J. Med.
Genet. 13: 15-25, 1982.
6. Maroteaux, P.; Stanescu, V.; Stanescu, R.: Four recently described
osteochondrodysplasias.In: Papadatos, C. J.; Bartsocas, C. S.: Skeletal
Dysplasias. New York: Alan R. Liss (pub.) 1982. Pp. 345-350.
7. Rimoin, D. L.; Sillence, D. O.; Lachman, R. S.; Jenkins, T.; Riccardi,
V.: Giant cell chondrodysplasia: a second case of a rare lethal newborn
skeletal dysplasia. (Abstract) Am. J. Hum. Genet. 32: 125A only,
1980.
8. Salonen, R.: Neonatal osseous dysplasia I: second report. Prog.
Clin. Biol. Res. 104: 171-172, 1982.
9. Sillence, D.; Kozlowski, K.: 'Giant cell' chondrodysplasia. (Letter) Am.
J. Med. Genet. 15: 627 only, 1983.
10. Sillence, D.; Kozlowski, K.; Rogers, J.; Sprague, P.; Cullity,
G.; Osborn, R.: Atelosteogenesis: evidence for heterogeneity. Pediat.
Radiol. 17: 112-118, 1987.
11. Sillence, D. O.; Lachman, R. S.; Jenkins, T.; Riccardi, V. M.;
Rimoin, D. L.: Spondylohumerofemoral hypoplasia (giant cell chondrodysplasia):
a neonatally lethal short-limb skeletal dysplasia. Am. J. Med. Genet. 13:
7-14, 1982.
12. Stern, H. J.; Graham, J. M., Jr.; Lachman, R. S.; Horton, W.;
Bernini, P. M.; Spiegel, P. K.; Bodurtha, J.; Ives, E. J.; Bocian,
M.; Rimoin, D. L.: Atelosteogenesis type III: a distinct skeletal
dysplasia with features overlapping atelosteogenesis and oto-palato-digital
syndrome type II. Am. J. Med. Genet. 36: 183-195, 1990.
13. Stevenson, R. E.; Wilkes, G.: Atelosteogenesis with survival
beyond the neonatal period. Proc. Greenwood Genet. Center 2: 32-38,
1983.
14. Temple, K.; Hall, C. A.; Chitty, L.; Baraitser, M.: A case of
atelosteogenesis. J. Med. Genet. 27: 194-197, 1990.
15. Whitley, C. B.; Burke, B. A.; Granroth, G.; Gorlin, R. J.: De
la Chapelle dysplasia. Am. J. Med. Genet. 25: 29-39, 1986.
16. Yang, S. S.; Roskamp, J.; Liu, C. T.; Frates, R.; Singer, D. B.
: Two lethal chondrodysplasias with giant chondrocytes. Am. J. Med.
Genet. 15: 615-625, 1983.
Clinical Synopsis:
INHERITANCE:
Isolated cases
GROWTH:
[Height];
Short-limbed dwarfism
HEAD AND NECK:
[Face];
Frontal bossing;
Micrognathia;
Midface hypoplasia;
[Eyes];
Prominent globes;
Edematous eyelids;
[Nose];
Depressed nasal bridge;
Hypoplastic nose;
[Mouth];
Cleft palate;
[Neck];
Short neck
RESPIRATORY:
[Larynx];
Laryngeal stenosis
CHEST:
[External features];
Narrow thoracic cage;
[Ribs, sternum, clavicles, and scapulae];
11 pairs of ribs
GENITOURINARY:
[Internal genitalia, male];
Cryptorchidism
SKELETAL:
[Spine];
Fused cervical vertebrae;
Abnormal segmentation;
Thoracic platyspondyly;
Coronal clefts;
Sagittal clefts;
[Limbs];
Rhizomelic limb shortening;
Elbow dislocation;
Short humeri with proximal clubbing and distal tapering;
Short, bowed radius;
Absent-hypoplastic ulnae;
Short femora with proximal clubbing and distal tapering;
Short, bowed tibiae;
Absent-hypoplastic fibulae;
[Hands];
Brachydactyly;
Poor ossifications of metacarpal and proximal, middle phalanges;
Well-ossified distal phalanges;
Short metacarpals;
[Feet];
Talipes equinovarus;
Short metatarsals
NEUROLOGIC:
[Central nervous system];
Encephalocele
PRENATAL MANIFESTATIONS:
[Amniotic fluid];
Polyhydramnios;
[Delivery];
Stillborn;
Premature delivery
LABORATORY ABNORMALITIES:
Giant cells (degenerating chondrocytes) in resting zone of epiphyseal
cartilage
MISCELLANEOUS:
All cases have been stillborn or immediate neonatal death
MOLECULAR BASIS:
Mutation in the FLNB gene (603381)
Contributors:
Kelly A. Przylepa - revised: 8/20/2002
Creation Date:
John F. Jackson: 6/15/1995
Edit Dates:
joanna: 03/14/2005
alopez: 3/23/2004
joanna: 8/20/2002
Contributors:
Marla J. F. O'Neill - updated: 3/16/2004
Creation Date:
Victor A. McKusick: 6/4/1986
Edit Dates:
carol: 10/25/2006
alopez: 4/2/2004
alopez: 3/23/2004
terry: 3/16/2004
carol: 11/24/1998
mimadm: 4/9/1994
carol: 11/22/1993
supermim: 3/16/1992
carol: 7/9/1991
carol: 2/21/1991
carol: 7/9/1990
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