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A number sign (#) is used with this entry because of the demonstration
that the Hunter-Thompson type of acromesomelic dysplasia is caused by
mutation in cartilage-derived morphogenetic protein-1 (CDMP1; 601146).
The forearms, hands, and feet are predominantly involved. Adult height
is about 120 cm. The radius is curved and its head is often dislocated
posteriorly. The metacarpals, metatarsals, and phalanges are
particularly short. The phalanges are almost square. Despite some
resemblances to pseudoachondroplastic dysplasia, epiphyseal and
metaphyseal changes of pseudoachondroplasia are missing. In 1 case
reported by Maroteaux et al. (1971), the parents were normal and first
cousins. In a second family, 2 sisters were affected. Beighton (1974)
observed the disorder in 5 sisters, the offspring of consanguineous
unaffected parents. Campailla and Martinelli (1971) described 2 sibs
with limb shortening, which was most pronounced in the forearms and
lower legs (as is characteristic of mesomelic dwarfism), associated with
dysplasia of the tubular bones of the hands and feet. In each of 2
sibships, 2 sisters were affected. The parents were double first cousins
in one of these. Intelligence was normal. The nose was somewhat pugged.
Precocious osteoarthritic changes developed in the hips. The patients
were dwarfed. See acrodysostosis (101800) and peripheral dysostosis
(170700). Langer et al. (1977) concluded that the 3 sib pairs reported
as peripheral dysostosis by Hall (1969) and the sisters reported as
recessive peripheral dysostosis by Goodman et al. (1974) actually had
acromesomelic dwarfism.
Langer et al. (1989) described a severe autosomal recessive form of
acromesomelic dysplasia which they called the Hunter-Thompson type
(AMDH). Abnormalities were limited to the limbs, with the middle and
distal segments being most affected and the lower limbs more affected
than the upper. Hunter and Thompson (1976) had reported a patient who
appeared to have had the same condition. In all 3 patients, dislocations
of the elbows and ankles were present; dislocations of the hips and
knees were present in 2. Langer et al. (1989) pointed to a similarity to
Grebe chondrodysplasia (AMDG; 200700), but concluded that radiologic
analysis demonstrated differences. Langer et al. (1989) also considered
the disorder to be distinct from the Maroteaux type (AMDM; 602875). The
distinctness of the Hunter-Thompson form of acromesomelic dysplasia was
proved by the demonstration of a mutation in cartilage-derived
morphogenetic protein-1 (CDMP1; 601146.0001) in the family reported by
Langer et al. (1989); see the report by Thomas et al. (1996), which
described the 22-bp tandem duplication in CDMP1. As indicated by this
report, abnormalities were limited to the limbs; the craniofacial and
axial skeleton was normal. The forearms and hands were relatively
shorter than the upper arms and the lower leg shorter than the thighs.
The feet were very short and the third, fourth, and fifth toes were
ball-shaped and functionless. Joint dislocations involved ankles, hips,
elbows, and knees.
Individuals with either AMDH or AMDG have normal axial skeletons and
missing or fused skeletal elements within the hands and feet. This
contrasts with the radiologic features of the Maroteaux type of
acromesomelic dysplasia. In patients with AMDM, all skeletal elements
are present, but they have abnormal rates of linear growth (Langer and
Garrett, 1980). In addition, axial skeletal involvement occurs in
individuals with AMDM, characterized by wedging of vertebral bodies,
with the dorsal margins being shorter than the ventral margins. These
clinical differences, which serve to distinguish AMDM from AMDH and
AMDG, suggested that AMDM is also genetically distinct. Kant et al.
(1998) demonstrated that AMDM maps to chromosome 9, and not to
chromosome 20 where the CDMP1 gene is located.
Clarke et al. (1995) reported bilateral central corneal opacities in a
patient with clinical and radiographic features consistent with
acromesomelic dysplasia. Transmission electron micrography of the cornea
demonstrated disorganization of collagen bundles secondary to the
accumulation of fibillogranular material, with increased cellularity and
abundant rough-surfaced endoplasmic reticulum in fibrocytes. Both
corneas showed scarring through 20% of the thickness, and the child was
successfully treated by full-thickness keratoplasty and corneal grafting
on the right and lamellar keratoplasty on the left.
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| References |
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Ortop. 22: 180-184, 1971.
- Clarke, W. N.; Munro, S.; Brownstein, S.; Agapitos, P.; Hughes-Benzie,
R.: Ocular findings in acromesomelic dysplasia. Am. J. Ophthal. 118:
797-804, 1995.
- Goodman, R. M.; Weinberg, U.; Hertz, M.; Rosenthal, T.; Hertz,
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- Grebe, H.: Die Achondrogenesis: ein einfach rezessives Erbmerkmal. Folia
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Bard, L. A.; Rissman, E. M.; Rogers, J. G.; Dorst, J. P.; Hall, J.
G.; Sparkes, R. S.; Franken, E. A., Jr.: Acromesomelic dwarfism:
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- Maroteaux, P.; Martinelli, B.; Campailla, E.: Le nanisme acromesomelique. Presse
Med. 79: 1839-1842, 1971.
- Thomas, J. T.; Lin, K.; Nandekar, M.; Camargo, M.; Cervenka, J.;
Luyten, F. P.: A human chondrodysplasia due to a mutation in a TGF-beta
superfamily member. Nature Genet. 12: 315-317, 1996.
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