Neonatal Dwarfism Research Articles

A rare case of neonatal dwarfism – Question

A rare case of neonatal dwarfism – Question

A CASE OF THANATOPHORIC DYSPLASIA TYPE I: THE FIRST CLINICOPATHOLOGIC REPORT FROM ETHIOPIA

ABSTRACTThanatophoric dysplasia (TD) is a short-limb neonatal dwarfism syndrome that is usually lethal in the perinatal period1. It is characterized by markedly underdeveloped skeleton and short-limb dwarfism. TD is caused by a mutation of the fibroblast growth factor receptor 3 gene (FGFR3), which is located on the short arm of chromosome 42,3.This study reports a neonate born at Tikur Anbessa Teaching Hospital with features of thanatophoric dysplasia which was proven radiologically and pathomorphologically. The mother presented to the hospital at 39 +1 weeks of gestational age with ultrasound diagnosis of achondroplasia. She developed cephalopelvic disproportion and underwent caesarian section. Outcome was an alive anomalous female neonate with a weight of 2900 gms of 4, 2, 2 & 0 in the 1st, 5th, 10th & 20th minute APGAR scores, respectively. The neonate expired due to severe respiratory distress despite resuscitation. The parturient died following pulmonary thromboembolism diagnosed on her second postoperative day.CONCLUSION: Thanatophoric dysplasia is a lethal skeletal anomaly which should be diagnosed and managed in the second trimester of pregnancy. Missing this case in the mid-trimester costed note only the physical, psychological and the economic burden but also the life of the mother. KEY WORDS: Thanatophoric dysplasia, fibroblast growth factor receptor 3 gene (FGFR3) (Ethiopian Journal of Reproductive Health 2018; 10; 3: 65-70)

Identification of a novel insertion mutation in FGFR3 that causes thanatophoric dysplasia type 1.

Thanatophoric dysplasia is a type of short-limbed neonatal dwarfism that is usually lethal in the perinatal period. It is characterized by short limbs, a narrow, bell-shaped thorax, macrocephaly with a prominent forehead, and flattened vertebral bodies. These malformations result from autosomal dominant mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. In this report, we describe a novel FGFR3 insertion mutation in a fetus with shortened limbs, curved femurs, and a narrow thorax. The diagnosis of thanatophoric dysplasia type 1 was suspected clinically, and FGFR3 sequencing showed a c.742_743insTGT variant, which predicts p.R248delinsLC. In vivo studies in zebrafish demonstrated that this mutation resulted in the overexpression of zebrafish Fgfr3, leading to the over-activation of downstream signaling and dorsalized embryos. To date, no insertions or deletions in FGFR3 have been reported to cause thanatophoric dysplasia types 1 or 2; therefore, this represents the first report to describe such a mutation. © 2016 Wiley Periodicals, Inc.

A case of thanatophoric dysplasia type I with an R248C mutation in theFGFR3gene

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.

Japanese Cases of Type 1 Thanatophoric Dysplasia Exclusively Carry a C to T Transition at Nucleotide 742 of the Fibroblast Growth Factor Receptor 3 Gene

Type I thanatophoric dysplasia (TD) is typically a lethal neonatal dwarfism, but a limited number of cases of type I TD cases survive more than one year, suggesting genetic heterogeneity. In this study, we analyzed the fibroblast growth factor receptor 3 (FGFR3) gene in 5 Japanese cases of type I TD with clinical symptoms ranging from lethal to long-survival. In every case, nucleotide sequence analysis of cDNA revealed a C to T transition at nucleotide 742 (C742T) in one allele of the FGFR3 gene, suggesting that type I TD is a rather homogeneous genetic condition, irrespective of clinical course. No association was found between C742T and C882T, although both nucleotides changes were from CpG dinucleotide in a near location.

Dysspondyloenchondromatosis in the newborn

Dysspondyloenchondromatosis is a rare form of generalised enchondromatosis with hypoplastic/dysplastic changes in the lower thoracic and upper lumbar spine. The disease presents at birth as neonatal dwarfism and is characterised later in life by marked shortening of stature, unequal length of the extremities and early development of kyphoscoliosis. We report four newborn babies--three boys and a girl--with dysspondyloenchondromatosis, who had skeletal survey performed shortly after birth. The condition can be established in the newborn, as the radiographic examination (skeletal survey) shows diagnostic radiographic findings.

Lethal neonatal short-limbed dwarfism

Lethal neonatal short-limbed dwarfism

A new neonatal short limbed dwarfism

Two siblings with the same short limbed neonatal dwarfism are reported. The patients died from pulmonary hypoplasia.

A Case of Short Rib Polydactyly

A patient with neonatal dwarfism had many characteristics of the Majewski syndrome, except for a cleft lip and abnormalities of internal organs. Absence of these anomalies and presence of more severe pathological changes in bone suggest either a wider spectrum for this disorder or a separate entity.

Ultrasonic Diagnosis of Thanatophoric Dwarfismin Utero

There are several types of short-limbed neonatal dwarfism. Before the delineation of thanatophoric dwarfism many dwarfs who died early in infancy were labeled "achondroplastic." Intrauterine radiological diagnosis is possible and the clinician may be alerted to the possibility of the condition by noting short squat limbs with a relatively large head on ultrasound examination, especially in cases of hydramnios.

Five cases of fatal neonatal dwarfism.

Five cases of fatal neonatal dwarfism.