Djeho, the Egyptian God's dancer with dwarfism from the thirtieth dynasty.

This manuscript presents some artistic and medical considerations about a representation of an individual with apparent dwarfism. He was found in Saqqara by the British Egyptologist James Edward Quibell, in 1910/11. The naked figure of this individual, Djeho, is carved in profile on the lid of his sarcophagus. He has a height of 120 cm and has characteristic clinical features suggesting achondroplasia.

Unique association of hypochondroplasia with craniosynostosis and cleft palate in a Mexican family.

Hypochondroplasia (HCH) is a skeletal dysplasia caused by an abnormal function of the fibroblast growth factor receptor 3. Although believed to be relatively common, its prevalence and phenotype are not well established owing to its clinical, radiological, and genetic heterogeneity. Here we report on a molecularly proven HCH family with an affected father and two children. The siblings (male and female) with HCH also had craniosynostosis and cleft palate, respectively. The present report supports the conclusion that the full clinical spectrum of HCH is not completely delineated. It also suggests that secondary, as yet unknown, modifying factors can influence the final phenotype.

Association of achondroplasia with sagittal synostosis and scaphocephaly in two patients, an underestimated condition?

We report on two patients with an unusual combination of achondroplasia and surgically treated sagittal synostosis and scaphocephaly. The most common achondroplasia mutation, p.Gly380Arg in fibroblast growth factor receptor 3 (FGFR3), was detected in both patients. Molecular genetic testing of FGFR1, FGFR2, FGFR3 and TWIST1 genes failed to detect any additional mutations. There are several reports of achondroplasia with associated craniosynostosis, but no other cases of scaphocephaly in children with achondroplasia have been described. Recently it has been demonstrated that FGFR3 mutations affect not only endochondral ossification but also membranous ossification, providing new explanations for the craniofacial hallmarks in achondroplasia. Our report suggests that the association of isolated scaphocephaly and other craniosynostoses with achondroplasia may be under recognized.

Increased first-trimester nuchal translucency associated with thanatophoric dysplasia type 1.

Thanatophoric dysplasia (TD) is the most frequent form of lethal skeletal dysplasia. Prenatal diagnosis is commonly accomplished in the second-trimester scan, but occasionally TD is found to be associated with increased nuchal translucency (NT) at first-trimester screening for aneuploidies. TD may not be clearly distinguished from the other skeletal dysplasias. A definite diagnosis can be established by molecular genetic analysis to find out the abnormal mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We reported a case of TD type 1 detected by first-trimester NT measurement, and confirmed by molecular analysis of FGFR3 gene using high-resolution melting analysis.

Improvement of molecular-genetic diagnostics of the most common skeletal dysplasias.

UNLABELLED: achondroplasia (ACH) and hypochondroplasia (HCH) into the routine practice. BACKGROUND: Both disorders are usually caused by de novo gain-of-function type mutations in FGFR3 gene encoding the fibroblast growth factor receptor 3, which plays an important role in the metabolism of connective tissues. More than 99% of ACH cases are caused by the glycine-to-arginine substitution at codon 380 and about 70% of HCH cases result from the asparagine-to-lysine/-serine/-threonine substitutions at codon 540 in the consequence of the four different possible nucleotide changes occurred at the same codon. METHODS: Exons 10 and 13 of the FGFR3 gene were analysed by PCR-RFLP and sequencing analysis. The exon 13 sequencing was necessary for mutation type specification. RESULTS: We confirmed the diagnosis of ACH due to 1138G→A transition in 7 patients and we identified 1620C→A transversion responsible for HCH in 2 patients. CONCLUSION: Due to serious limitations in recently used methods, we had to modify the molecular-genetic diagnostics approach. We developed the reliable diagnostics and made it available for achondroplasia and hypochondroplasia suspected patients (Tab. 1, Ref. 5, Ref. 17).

Achondroplasia: Clinical, Radiological and Molecular Profile from Rare Disease Centre, India.

Achondroplasia is the most common autosomal dominant form of skeletal dysplasia and is caused by heterozygous mutations of the fibroblast growth factor receptor 3 ( FGFR3 ) gene at region 4p16.3. This study highlights the data of achondroplasia cases, clinical spectrum, and their outcome from small cities and the region around Rajasthan. The data for analysis were collected retrospectively from genetic records of rare disease clinic in Rajasthan. Clinical profile, radiographic features, molecular test results, and outcome were collected. There were 15 cases, including eight males and seven females, in this cohort. All had facial hypoplasia, depressed nasal bridge, prominent forehead, and characteristic radiographic features. A total of 14 cases were sporadic and one case was inherited from the mother. Mutation analysis showed 13 out of 15 cases with the p.Gly380Arg mutation in the FGFR3 gene. Hydrocephalus was developed in three cases, required shunting in two cases.

Heterozygous variant in FGFR3 underlying severe phenotypes in the second trimester: a case report.

BACKGROUND: Achondroplasia is a congenital skeletal system malformation caused by missense variant of FGFR3 gene with an incidence of 1 per 20,000-30,000 newborns, which is an autosomal dominant inheritance disease. Despite similar imaging features, the homozygous achondroplasia is absolutely lethal due to thoracic stenosis, whereas heterozygous achondroplasia does not lead to fetal death. CASE PRESENTATION: A fetus with progressive rhizomelic short limbs and overt narrow chest was detected by prenatal ultrasound in the second trimester. Gene sequencing results of amniotic fluid sample indicated a rare missense variant NM_000142.4: c.1123G > T(p.Gly375Cys), leading to a glycine to cysteine substitution. Re-sequencing confirmed that it was a heterozygous variant, and thoracic stenosis was then confirmed in the corpse by radiological examination. CONCLUSIONS: We identified a heterozygous variant of the FGFR3 gene as the rare pathogenic variant of severe achondroplasia in a fetus. Heterozygous variants of p.Gly375Cys may have a severe phenotype similar to homozygote. It's crucial to combine prenatal ultrasound with genetic examination to differentiate heterozygous from homozygous achondroplasia. The p.Gly375Cys variant of FGFR3 gene may serve as a vital target for the diagnosis of severe achondroplasia.

Does the co-occurrence of FGFR3 gene mutation in hypochondroplasia, medial temporal lobe dysgenesis, and focal epilepsy suggest a syndrome?

BACKGROUND: Hypochondroplasia is a rare skeletal dysplasia characterized by disproportionately short stature, lumbar lordosis, and limited extension of the elbow caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that plays a role in controlling nervous system development. Hypochondroplasia with FGFR3 mutation associated with bilateral medial temporal lobe anomalies and focal epilepsy was previously reported in several patients. PATIENT: We report clinical, electroclinical, and neuroradiological findings of one patient affected by hypochondroplasia. RESULTS: Clinical diagnosis was confirmed by molecular analysis of the FGFR3 gene, which showed a N540 K mutation. The patient had normal psychomotor development and showed early-onset focal seizures with left temporal localization on interictal and ictal electroencephalograph. The seizures were well controlled, and the patient has been seizure-free since infancy. Magnetic resonance imaging showed abnormal anteriorly posteriorly infolding in the hippocampus and abnormally oriented parahippocampus sulci, and additional cortical rim dysplasia with gray-white matter junction blurring in the hippocampus. CONCLUSIONS: The present case of hypochondroplasia and FGFR3 mutation in Asn540Lys associated with characteristic abnormalities involving bilaterally medial temporal lobe structures, probable hippocampal cortex focal dysplasia, and early onset of focal epilepsy underscores the possibility of a rare syndrome.

A case of thanatophoric dysplasia type I with an R248C mutation in the FGFR3 gene.

Thanatophoric dysplasia (TD) is a short-limb neonatal dwarfism syndrome that is usually lethal in the perinatal period. It is characterized by shortening of the limbs, severely small thorax, large head with a prominent forehead, macrocephaly, curved femur, and flattened vertebral bodies. These malformations result from the mutation in fibroblast growth factor receptor 3 (FGFR-3) gene which is located on the short arm of chromosome 4. A definite diagnosis should be established by molecular genetic analysis to find out the abnormal mutations in the FGFR3 gene. We confirmed by detection of a R248C mutation in the FGFR3 gene in DNA analysis.