Campomelic Dysplasia: Echographic Suspicion in the First Trimester of Pregnancy and Final Diagnosis of Two Cases

Abstract

Objective: Campomelic dysplasia (CD) is a rare skeletal dysplasia characterized by marked femoral and tibial angulations, hypoplasic scapulae, normal upper limbs and sex reversal in 3/4 of 46,XY fetuses. Most cases are lethal in the neonatal period. Heterozygous mutations in the SOX9 gene are responsible for CD. The diagnosis is not usually made until the mid-second trimester or later. Methods: We describe 2 cases of CD suspected by ultrasonography in the first trimester. Results: The 2 cases presented with hygroma colli along with anomalies in the lower but not the upper limbs. Terminations of pregnancy were obtained at 14+3 and 20+6 gestational weeks. Fetopathological examinations confirmed sonographic findings. Conclusion: When first trimester hygroma colli is accompanied by specific findings of the lower limbs, the diagnosis of CD can be investigated through SOX9 mutation analysis.

Early ultrasound suspect of thanatophoric dysplasia followed by first trimester molecular diagnosis

“…Despite the high number of clinically defined bone dysplasias, only a limited collection of them may present in the early prenatal period with abnormal ultrasound. After careful scrutiny of the literature, we were able to identify first trimester prenatally diagnosed cases belonging to TDs [Ferreira et al, 2004;De Biasto et al, 2005;Beuke et al, 2010;Tonni et al, 2010], atelosteogenesis group (i.e., atelosteogenesis type 1, 2, and 3, and boomerang dysplasia) [Fernandez-Aguilar et al, 2005;Cordier et al, 2008], perinatal/ lethal hypophosphatasia [Tongsong and Pongsatha, 2000], campomelic dysplasia [Michel-Calemard et al, 2004;Massardier et al, 2008], achondrogenesis type 1A and B and 2 [Soothill et al, 1993;Meizner and Barnhard, 1995], short rib (-polydactyly) group (i.e., short rib-polydactyly type I, II, III, and IV, Ellis-van Creveld syndrome, Jeune syndrome and severe forms of oro-facial-digital syndromes) [Hill and Leary, 1998;Den Hollander et al, 2001;Dugoff et al, 2001;R€ osing et al, 2008], and Blomstrand dysplasia [Den Hollander et al, 1997]. In theory, other lethal osteocondrodysplasias, such as some platyspondylic lethal chodrodysplasias, Schneckenbecken and Greenberg dysplasias, are so severe to determine first trimester fetal anomalies, but we failed to identify such cases in the literature.…”

A rare case of lethal campomelic dysplasia

“…The head is macrocephalic with a flattened face and nasal bridge, high forehead, low-set ears often with associated deafness, hypertelorism, long philtrum, small mouth, and micrognathia. 3 Cardiac diseases like ventricular and atrial septal defects, tetralogy of Fallot, and patent ductus arteriosus can also be detected. In addition, a group of respiratory anomalies that includes lungs and chest of a small size, narrow air-passages, tracheomalacia, laryngomalacia associated with cleft palate, micrognathia, and hypotonia may be present.…”

“…There is no sex discrimination, as the male-tofemale ratio of campomelic dysplasia incidence is 1:1; however, 75% of genotypic XY males show female or indefinite genitalia. 3 To date there are only a few reports on the skeletal features of campomelic syndrome in the literature. 12 To our knowledge, all reported cases of CD are the results of natural conception while in our case this pregnancy was achieved by assisted reproductive technology.…”

“…In addition, hydrocephalus, hydronephrosis, and congenital heart disease (ventriculoseptal defect, atrioseptal defect, aortic stenosis, and/or tetralogy of Fallot) are also present. 3 Another feature of CD is male-to-female sex reversal, which occurs in about twothirds of patients with an XY karyotype. 3 Antenatal ultrasound scanning at about 18 to 20 weeks of gestation permits the detection of large number of major fetal structural anomalies.…”

“…3 Another feature of CD is male-to-female sex reversal, which occurs in about twothirds of patients with an XY karyotype. 3 Antenatal ultrasound scanning at about 18 to 20 weeks of gestation permits the detection of large number of major fetal structural anomalies. 4 A considerable proportion of males requiring intracytoplasmic sperm injection (ICSI) have a very low sperm count, which is associated with a greater risk of chromosomal abnormalities.…”