Lethal neonatal chondrodysplasias in the west of scotland 1970–1983 with a description of a thanatophoric, dysplasialike, autosomal recessive disorder, glasgow variant

Abstract

Complete ascertainment of lethal neonatal short-limb chondrodysplasias was attempted in the West of Scotland for the period 1970-1983. Forty-three cases were identified, representing a minimum incidence of 1 in 8,900. The differential diagnosis included 11 well-delineated skeletal dysplasias, one case of warfarin embryopathy, and one apparently new condition with presumed autosomal recessive inheritance that has radiographic similarities to those of thanatophoric dysplasia (TD). In this series TD had an incidence of 1 in 42,221, which is consistent with new dominant mutation at a rate of 11.8 +/- 4.1 X 10(-6) mutations per gene per generation. Ultrasonic measurement of fetal long bone length was performed in eight subsequent pregnancies at risk. Five unaffected fetuses were predicted correctly and three affected fetuses were detected during the second trimester (one with rhizomelic chondrodysplasia punctata-second trimester prenatal diagnosis not previously reported; one with achondrogenesis type II; and one with the new lethal condition).

Length of life and treatment intensity in infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal

“…First, we elicited the expert opinion of knowledgeable clinicians (three perinatologists, three neonatologists, one geneticist and two genetics counselors) who reviewed International Classification of Diseases, Ninth Revision codes (ICD-9 codes 740 to 759) 5 and identified the congenital diagnoses they considered lethal. We then performed MEDLINE and Google searches of the diagnoses listed by two-thirds or more of the clinicians, reviewed articles, [6][7][8][9][10][11][12][13][14][15][16] reference texts 17 and websites, 18,19 and retained those diagnoses that were consistently reported to be associated with death before a year of life in nearly all (X85%, when statistics were available) cases. We excluded conjoined twins because of the confounding effect of one infant's condition on the other.…”

Perinatal lethal skeletal dysplasia: a case report

“…The three most common lethal skeletal dysplasias are thanatophoric dysplasia (TD, 29 percent), 3 osteogenesis imperfect Type 2 (14 percent), and achondrogenesis (9 percent), 4 which account for 40 to 60 percent of all lethal skeletal dysplasias. 1 Perinatal type hypophosphatasia, chondroectodermal dysplasia, campomelic dysplasia, and Jeune asphyxiating thoracic dysplasia are also among the more common lethal skeletal dysplasias.…”

Tibial Agenesis and Gollop-Wolfgang Complex in Three Siblings Born to an Epileptic Woman Treated with Carbamazepine: Teratogenicity

“…The management of epilepsy during pregnancy requires a balance between control of the mother and the risks involved in uncontrolled seizures, versus the teratogenecity of antiepileptic drugs [13]. Furthermore, folate supplementation has been shown to reduce congenital defects [14]. Sodium valproate has been implicated in most of these cases of congenital malformations [13][14][15] but till date, carbamazepine has not been directly implicated in GWC.…”

“…Furthermore, folate supplementation has been shown to reduce congenital defects [14]. Sodium valproate has been implicated in most of these cases of congenital malformations [13][14][15] but till date, carbamazepine has not been directly implicated in GWC.…”