Congenital malformations, deformations and chromosomal abnormalities
Congenital malformations and deformations of the musculoskeletal system
Autosomal dominant
4p16.3
Achondroplasia is the most common form of human dwarfism. It is characterised by rhizomelic short stature, macrocephaly with an abnormal cranial base, midface hypoplasia, lumbar lordosis and short limbs. The condition is caused by mutations in the FGFR3 gene. About 80% of affected individuals result from sporadic mutations without positive family histories.
| Subject ID | Country | Sex | Family History | Parental Consanguinity | HPO Terms | Variant | Zygosity | Mode of Inheritance | Reference | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|
| 100800.1.1 | Arab | Unknown | No | Disproportionate short stature; Macroce... Disproportionate short stature; Macrocephaly; Abnormality of the skull base; Midface retrusion; Depressed nasal bridge; Hyperlordosis; Small hand; Limited elbow extension  | NM_000142.5:c.1138G>A | Heterozygous | Autosomal, Dominant | Falik-Zaccai et al. 2000 | ||
| 100800.2 | Lebanon | Unknown | Yes | | NM_000142.4:c.2419T>G | Heterozygous | Autosomal, Dominant | Jalkh et al. 2019 | ||
| 100800.3 | United Arab Emirates | Male | No | Yes | Global developmental delay; Short stature Global developmental delay; Short stature | NM_000142.5:c.1138G>A | Heterozygous | Saleh et al. 2021 | de novo mutation | |
| 100800.4 | Saudi Arabia | Male | Yes | Delayed speech and language development;... Delayed speech and language development; Short stature; Relative macrocephaly | NM_000142.5:c.1138G>A | Heterozygous | Autosomal, Dominant | Maddirevula et al. 2018 | De novo mutation | |
| 100800.5 | Saudi Arabia | Male | No | Short stature; Frontal bossing; Trigonoc... Short stature; Frontal bossing; Trigonocephaly; Rhizomelia; Osteopenia; Kyphosis | NM_000142.5:c.1138G>A | Heterozygous | Autosomal, Dominant | Maddirevula et al. 2018 | De novo mutation | |
| 100800.6 | Saudi Arabia | Female | No | Short stature; Macrocephaly Short stature; Macrocephaly | NM_000142.5:c.1138G>A | Heterozygous | Autosomal, Dominant | Maddirevula et al. 2018 | De novo mutation | |
| 100800.7 | Saudi Arabia | Female | Depressed nasal bridge; Relative macroce... Depressed nasal bridge; Relative macrocephaly; Frontal bossing; Midface retrusion | NM_000142.5:c.1138G>A | Heterozygous | Autosomal, Dominant | Maddirevula et al. 2018 | Mutation is de novo.... | ||
| 100800.8 | Saudi Arabia | Female | Yes | Macrocephaly; Short stature; Global deve... Macrocephaly; Short stature; Global developmental delay; Midface retrusion | NM_000142.5:c.1138G>A | Heterozygous | Autosomal, Dominant | Maddirevula et al. 2018 | De novo mutation | |
| 100800.G.1 | Arab; Algeria; Iraq; M... | Unknown | No | Disproportionate short stature; Macroce... Disproportionate short stature; Macrocephaly; Abnormality of the skull base; Midface retrusion; Depressed nasal bridge; Hyperlordosis; Small hand; Limited elbow extension | NM_000142.4:c.1138G>C | Heterozygous | Autosomal, Dominant | Falik-Zaccai et al. 2000 | Group comprising of ... |
Al-Gazali et al. (2003) defined the pattern and birth prevalence of the different types of osteochondrodysplasias in the United Arab Emirates. The cohort consisted of 88% Arabs.
Kozma (2006) described some of the earliest biological evidence of dwarfism from ancient Egypt, dating as far back as 4500 BCE.
Pusch et al. (2004), reported the screening of ancient bone samples for diagnostic achondroplasia mutations. The FGFR3 mutation c.1138G>A was detected in a dry mummy of short stature from the Semerchet tomb, dating approximately 4890-5050 BP.
Bittar (1998) studied 3865 consecutive newborns delivered between 1991 and 1993 and found major congenital anomalies in 64 cases. Many of these cases had achondroplasia.
Eapen et al. (1998) carried out a screening program for learning disorders in Al-Ain and identified one case with achondroplasia.
Hosani and Czeizel (2000) reported that out of a total of 4,861 births recorded between March and May of 1998, achondroplasia was identified in one neonate, resulting in an incidence rate of 0.21 per 1,000 births.