Fraser Syndrome: Epidemiological Study in a European Population

Abstract

Fraser syndrome is a rare autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, laryngeal, and urogenital malformations. We present a population-based epidemiological study using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network of birth defect registries. Between January 1990 and December 2008, we identified 26 cases of Fraser syndrome in the monitored population of 12,886,464 births (minimal estimated prevalence of 0.20 per 100,000 or 1:495,633 births). Most cases (18/26; 69%) were registered in the western part of Europe, where the mean prevalence is 1 in 230,695 births, compared to the prevalence 1 in 1,091,175 for the rest of Europe (P = 0.0003). Consanguinity was present in 7/26 (27%) families. Ten (38%) cases were liveborn, 14 (54%) pregnancies were terminated following prenatal detection of a serious anomaly, and 2 (8%) were stillborn. Eye anomalies were found in 20/24 (83%), syndactyly in 14/24 (58%), and laryngeal anomalies in 5/24 (21%) patients. Ambiguous genitalia were observed in 3/24 (13%) cases. Bilateral renal agenesis was present in 12/24 (50%) and unilateral in 4/24 (17%) cases. The frequency of anorectal anomalies was particularly high (42%). Most cases of Fraser syndrome (85%) are suspected prenatally, often due to the presence of the association of renal agenesis and cryptophthalmos. In the European population, a high proportion (82%) of pregnancies is terminated, thus reducing the live birth prevalence to a third of the total prevalence rate.

Congenital unilateral renal agenesis: Prevalence, prenatal diagnosis, associated anomalies. Data from two birth‐defect registries

“…Regarding extra‐renal anomalies, we observed in our series that URA was part of a well‐identified syndrome in 30% of cases, of which VACTERL association and Fraser syndromes were the more frequent. These associations are also widely reported in adult series (Dursun et al, ; Akl, ; Barisic et al, ; Cunningham et al, ; Westland et al, ).…”

Oral manifestations and rehabilitation in Fraser syndrome: A case report

“…Fraser syndrome (FS) is a rare autosomal recessive malformation disorder characterized by craniofacial dysmorphism, cryptophthalmos, cutaneous syndactyly, and abnormalities of the larynx. Mental retardation, congenital abnormalities of the urogenital tract, and cardiac abnormalities are also found in some individuals with FS . Mutations in the FRAS1 , FREM2 , and GRIP1 genes have been identified as causes of FS …”

Reconstruction of Unilateral Incomplete Cryptophthalmos in Fraser Syndrome

“…1 While 85% of cases can be detected prenatally with ultrasound, the diagnosis can be made at birth with classic phenotypic features. 1 Cryptophthalmos is thought to arise embryologically from the failure of complete surface ectoderm differentiation in the development of the eyelids and lack of invagination to develop the lens.…”

“…1 While 85% of cases can be detected prenatally with ultrasound, the diagnosis can be made at birth with classic phenotypic features. 1 Cryptophthalmos is thought to arise embryologically from the failure of complete surface ectoderm differentiation in the development of the eyelids and lack of invagination to develop the lens. 6 The normal progression of eyelid development occurs through 5 stages in utero between gestational weeks 6 to 28: creation of eyelid folds, fusion of the eyelids, creation of specialized eyelid adnexal structures, eyelid separation, and maturation.…”

“…Ocular congenital anomalies can occur in up to 83% of patients and manifest most commonly as cryptophthalmos and microphthalmos. 1 While surgical reconstruction to improve visual acuity up to 20/100 has been reported, visual prognosis is typically poor. 2 There are few reports in the literature detailing surgical approaches to managing the ocular and periocular findings in Fraser syndrome.…”