The population‐based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US

Abstract

There have been no large population-based studies of the prevalence of achondroplasia and thanatophroic dysplasia in the United States. This study compared data from seven population-based birth defects monitoring programs in the United States. We also present data on the association between older paternal age and these birth defects, which has been described in earlier studies. The prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 livebirths (1/27,780-1/16,670 livebirths). The prevalence of thanatophoric dysplasia ranged from 0.21 to 0.30 per 10,000 livebirths (1/33,330-1/47,620 livebirths). In Texas, fathers that were 25-29, 30-34, 35-39, and > or =40 years of age had significantly increased rates of de novo achondroplasia among their offspring compared with younger fathers. The adjusted prevalence odds ratios were 2.8 (95% CI; 1.2, 6.7), 2.8 (95% CI; 1.0, 7.6), 4.9 (95% CI; 1.7, 14.3), and 5.0 (95% CI; 1.5, 16.1), respectively. Using the same age categories, the crude prevalence odds ratios for de novo cases of thanatophoric dysplasia in Texas were 5.8 (95% CI; 1.7, 9.8), 3.9 (95% CI; 1.1, 6.7), 6.1 (95% CI; 1.6, 10.6), and 10.2 (95% CI; 2.6, 17.8), respectively. These data suggest that thanatophoric dysplasia is one-third to one-half as frequent as achondroplasia. The differences in the prevalence of these conditions across monitoring programs were consistent with random fluctuation. Birth defects monitoring programs may be a good source of ascertainment for population-based studies of achondroplasia and thanatophoric dysplasia, provided that diagnoses are confirmed by review of medical records.

Development in children with achondroplasia: a prospective clinical cohort study

“…1 The primary biomechanical and anatomical differences seen in individuals with achondroplasia, which include marked limb shortening (more evident proximally than distally), macrocephaly, ligamentous laxity, and hypotonia, are known to contribute to developmental delays in motor skills, particularly during the first 2 years. [2][3][4][5][6][7] The delays seen in achievement of motor milestones indicate a clear need for achondroplasia-specific developmental trajectories against which to measure milestone attainment, allowing children to be compared directly with their peers.…”

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.…”

Prenatal diagnosis ultrasonographic thanatophoric dysplasia: report of a case

“…La displasia tanatofórica es una forma letal de enanismo, en la que la muerte ocurre generalmente en el período perinatal, debido a la insuficiencia respiratoria [1][2][3][4][5][6][7] al igual que el paciente descrito en este artículo. Es una enfermedad potencialmente diagnosticada durante el embarazo 1-7 y en este caso, las características determinadas en la exploración fetal permitieron el reconocimiento.…”

“…En casos sospechosos o en caso de duda, todavía existe la posibilidad de hacer el diagnóstico molecular basado en material obtenido por amniocentesis o muestreo de sangre fetal 9 . Al examinar al paciente al nacer, por lo general se observa hipotonía, macrocefalia, amplia fontanela anterior, abombamiento frontal, cara plana con ojos saltones y puente nasal bajo, tórax estrecho, con costillas cortas, abdomen protuberante, marcado acortamiento de las extremidades (micromelia) con pliegues cutáneos redundantes, manos en tridente (braquidáctil) y fémures cortos [1][2][3][4][5][6][7] . Por otro lado, los rayos X por lo general muestran cráneo en formato de hoja de trébol, platispondilia, el acortamiento de miembros orhizomelia por irregularidad en la metáfisis de los huesos largos sobre todo el fémur y anormalidades del sistema nervioso central tales como malformación del lóbulo temporal, hidrocefalia, hipoplasia del tallo cerebral, trastornos de la migración neuronal y foramen magno pequeño con la consiguiente compresión del tronco cerebral [1][2][3][4][5][6][7] .…”