Thanatophoric dysplasia. Correlation among bone X-ray morphometry, histopathology, and gene analysis

Abstract

The correlated observations of X-ray morphometry, histopathology, and gene analysis prompted the following diagnostic workup for TD: (1) prenatal sonography suspicion of skeletal dysplasia; (2) post-mortem X-ray morphometry for provisional diagnosis; (3) confirmation by genetic tests (hot-spot exons 7, 10, 15, and 19 analysis with 80-90% sensibility); (4) in negative cases if histopathology confirms TD diagnosis, research of rare mutations through sequential analysis of FGFR3 gene.

Perinatal Diagnostic Approach to Fetal Skeletal Dysplasias: Six Years Experience of a Tertiary Center

“…Thanatophoric dysplasia (OMIM 187600) is the most frequent sporadic lethal skeletal dysplasia with a prevalence of about 1 in 17 000-50 000 births [1]. Characteristic features of TD include markedly shortened limbs, narrow thorax with short ribs but normal trunk length, macrocephaly with frontal bossing, and low depressed nasal bridge [1,24]. It has been shown that expected mutations in TD include p.Arg248Cys, p.Tyr373Cys and p.Lys650Glu mutations [23].…”

“…All of the dysplasias display common phenotypic characteristics with different grades of severity [22]. (1) Pulmonary hypoplasia, immature kidneys Osteogenesis imperfecta (1) Cliteromegaly, immature kidneys Jarcho-Levin syndrome (1) Pulmonary hypoplasia Arthrogryposis (1) Agenesis of cerebellum, dilatation of bilateral cerebral ventricules, hypoplasia of psoas muscle Dysostosis (24) Abdominal wall: Omphalocele, gastroschisis Craniofacial: cleft-lip and palate, dysplastic ears, micrognathia, low-set ears, depressed nasal bridge, agenesis of external auditory channel, agenesis of the nose, agenesis of right eye-lid. Categorizing SDs is important because some of them are lethal.…”

Displasias esqueléticas: Reporte de un caso y revisión de la literatura

“…Un estudio publicado en 2014 muestra que la identificación prenatal de displasia del lóbulo temporal podría ayudar en la identificación de DT, demostrado su presencia en el 67% de los casos analizados. Esto ha sido corroborado posteriormente por otros trabajos (17,(19)(20)(21). La tomografía computada 3D prenatal contribuye al diagnóstico y podría tener un rol complementario a la US (22).…”

Thanatophoric dysplasia: A review

“…If hot spot exons are negative, then a search for rare mutations using sequential analysis of FGFR3 gene is performed. [37] The nucleotide sequence of FGFR3 is highly conserved between man and mouse.…”

“…Interplay between mechanical factors and the effects of the underlying mutation are additional factors in this process. [9] …”