Hypochondroplasia

Alternative Names

  • HCH
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations and deformations of the musculoskeletal system

OMIM Number

146000

Mode of Inheritance

Autosomal dominant

Gene Map Locus

4p16.3

Description

Hypochondroplasia is an autosomal dominant skeletal dysplasia sharing many phenotypic features, such as apparent rhizomelia, limitation of elbow extension, tibial bowing, exaggerated lumbar lordosis, metaphyseal flaring, shortening of the pedicles, narrowing of the lumbar interpediculate distance, squared ilia, shortened femoral necks, brachydactyly, macrocephaly, and distinctive facial features, with achondroplasia. However, in hypochondroplasia these features tend to be milder, and some are often subtle or absent. For these reasons, the diagnosis is frequently not made until later in childhood, when growth delay is first noted.

Hypochondroplasia is caused by mutation in the gene for fibroblast growth factor receptor-3 mapped to chromosome 4p16.3. FGFR3 is a member of the tyrosine kinase receptor family. The four known members (FGFR1-4) of this family play important roles in the regulation of proliferation, differentiation, and angiogenesis, as well as other processes involved in growth and development. Structurally, they comprise three extracellular immunoglobulin-like domains (Ig-like domains I-III), one transmembrane domain, and a split intracellular tyrosine kinase domain. FGFR3 is expressed during skeletal growth and endochondral ossification. FGFR3 seems to have a specific role as negative regulator of bone growth, and the known FGFR3 mutations result in a ligand independent activation of the receptor.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
146000.1.1Saudi ArabiaMaleYesNo Disproportionate short stature... NM_000142.5:c.1620C>GHeterozygousAutosomal, DominantMaddirevula et al. 2018
146000.1.2Saudi ArabiaFemaleYesNo Disproportionate short stature... NM_000142.5:c.1620C>GHeterozygousAutosomal, DominantMaddirevula et al. 2018 Relative of 146000.1...
146000.2Saudi ArabiaMaleNo Disproportionate short stature; Relative... NM_000142.5:c.1620C>AHeterozygousAutosomal, DominantMaddirevula et al. 2018 De novo mutation
146000.3.1Saudi ArabiaMaleYesNo Short stature; Delayed speech and langua... NM_000142.5:c.1620C>AHeterozygousAutosomal, DominantMaddirevula et al. 2018
146000.3.2Saudi ArabiaMaleYesNo Short stature; Delayed speech and langua... NM_000142.5:c.1620C>AHeterozygousAutosomal, DominantMaddirevula et al. 2018 Relative of 146000.3...

Other Reports

United Arab Emirates

Al Talabani et al. (1998) studied the pattern of major congenital malformations in 24,233 consecutive live and stillbirth in Corniche hospital, which is the only maternity hospital in Abu Dhabi, between January 1992 to January 1995. A total of 401 babies (16.6/1,000), including 289 Arabs, were seen with major malformation. Single gene disorders accounted for 24% of the cases, 21% were due to autosomal dominant disorders. In their study, Al Talabani et al. (1998) observed two cases of hypochondroplasia in families from the United Arab Emirates. Recurrence was reported in other members of the families. Al Talabani et al. (1998) concluded that this study is very close to representing the true incidence of congenital abnormalities in the whole United Arab Emirates, as this study included over 98% of deliveries in Abu Dhabi, the capital of United Arab Emirates.

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