Ocular findings in Fryns syndrome

Fryns syndrome is a rare, generally lethal, autosomal recessive multiple congenital anomaly (MCA) syndrome first described in 1979. Patients with the syndrome present with the classical findings of cloudy cornea, brain malformations, diaphragmatic defects, and distal limb deformities. Over 70 patients have been reported revealing a wide variety of phenotypic features. Although initially considered a major feature of Fryns syndrome, cloudy cornea has been relegated as a minor diagnostic sign and not commonly reported in patients since the original description. However, eye findings per se are not uncommon. Abnormal eye findings occasionally reported in Fryns syndrome potentially result in amblyopia and blindness, profoundly affecting neurologic outcome of those who survive the neonatal period. We reviewed 77 reported patients with Fryns syndrome and summarized the abnormal eye findings identified in 12 of the reported cases. In addition, we contribute three new patients with Fryns syndrome, one of which demonstrated unilateral microphthalmia and cloudy cornea.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Eye abnormalities in Fryns syndrome

Pierson

Taboada

Butler

2003

“…The remaining 52 cases had at least two or three of the diagnostic guidelines listed by Fryns in Table I [Fitch et al, 1978 (one case); Fryns et al, 1979 (two cases); Goddeeris et al, 1980 (one case); Lubinsky et al, 1983 (two cases); Meinecke and Fryns, 1985 (one case); Samueloff et al, 1987 (four cases); Moerman et al, 1988 (two cases); Aymé et al, 1989 (eight cases); Bamforth et al, 1989 (five cases); Cunniff et al, 1990 (four cases); Rodríguez Gonzalez et al, 1990 (one case); Dix et al, 1991 (one case); Kershisnik et al, 1991 (two cases); Bulas et al, 1992 (one case); Pellissier et al, 1992 (two cases); Gadow et al, 1994 (one case); Langer et al, 1994 (one case); Pinar et al, 1994 (three cases); Barthé et al, 1995 (one case); Bartsch et al, 1995 (two cases); Van Hove et al, 1995 (one case); Manouvrier‐Hanu et al, 1996 (one case); Fryns and Moerman, 1998 (one case); Cursiefen et al, 2000 (one case); Vargas et al, 2000 (two cases); Davis and Samarakkody, 2002 (one case)]. We determined the frequencies of the phenotypic features found in these cases [Tables II–XIII].…”

Section: Methodsmentioning

confidence: 99%

Fryns syndrome: A review of the phenotype and diagnostic guidelines

Slavotinek

2003

105

Fryns syndrome (FS) is the commonest autosomal recessive syndrome associated with congenital diaphragmatic hernia (CDH) and comprises CDH, pulmonary hypoplasia, craniofacial anomalies, distal limb hypoplasia, and internal malformations. Although there have been more than 50 case reports on probands with FS, the diagnostic guidelines were formulated from a review of eight patients and modifications to the guidelines have only once been suggested. Recently, several case reports have described new anomalies in FS and other papers have highlighted the variation in expressivity found in FS. This paper examines the medical literature on FS to define the phenotype and to review the diagnostic guidelines. We conclude that CDH with brachytelephalangy and/or nail hypoplasia is strongly suggestive of the diagnosis and that pulmonary hypoplasia, craniofacial dysmorphism, orofacial clefting, and polyhydramnios are sufficiently frequent to be diagnostically useful. Other distinctive malformations that are consistent with FS include ventricular dilatation or hydrocephalus, agenesis of the corpus callosum, neuronal or cerebellar heterotopias, abnormalities of the aorta, renal cysts, dilatation of the ureters, bicornuate uterus, renal dysplasia, proximal thumbs, and broad clavicles.

“… In addition to patients with a CVM reported on Tables II and III, patients without a CVM were reviewed [Goddeeris et al, 1980; Lubinsky et al, 1983; Meinecke and Fryns, 1985; Young et al, 1986; Samueloff et al, 1987; Willems et al, 1991; Hansen et al, 1992; Di Meglio et al, 1994; Wilgenbus and Majewski, 1994; Van Wymersch et al, 1996; Cursiefen et al, 2000; Davis and Samarakkody, 2002; Mengshol and Ornovold, 2003]. …”

Section: Resultsmentioning

confidence: 99%

Cardiovascular malformations in Fryns syndrome: Is there a pathogenic role for neural crest cells?

Lin

Pober

Mullen

et al. 2005

We performed a comprehensive literature and case report review to characterize the cardiovascular malformations (CVMs) associated with Fryns syndrome (OMIM #229850), a multiple congenital anomaly/mental retardation syndrome consisting of diaphragmatic defects, significant pulmonary hypoplasia, distinctive facial appearance, distal digital hypoplasia, and numerous other external and internal anomalies. A total of 112 patients meeting diagnostic guidelines for Fryns syndrome were identified, of whom 82 met narrowly defined criteria (Group I) and 30 met broader diagnostic criteria (Group II). Twelve patients reported as having Fryns syndrome with atypical features (Group III) were also analyzed. A CVM was reported in 51% (42 of 82) of Group I patients, most commonly an atrial or ventricular septal defect (VSD) (23 of 42, 55%). Conotruncal and aortic arch CVMs were common (11 of 42, 26%), but not significantly so compared to the general population of infants to age 1 year [Ferencz et al., 1997]. Recognizing that minor septal defects associated with congenital diaphragmatic hernia (CDH) may occur in response to altered hemodynamics (instead of being a bonafide CVM), we excluded four patients reported as having hemodynamically insignificant VSDs. Following these exclusions, conotruncal CVMs were found more commonly than in the general population (11 of 38, 29%, P < or = 0.025). In Group II, 9 of 30 (30%) had a CVM with no predominant type among the small number of cases reviewed. Among the atypical Fryns syndrome patients in Group III, half (6 of 12, 50%) had a CVM; most (4 of 6, 67%) were conotruncal, in particular, type B interrupted aortic arch (3 of 4). Patients with Fryns syndrome have a high rate of CVMs, warranting thorough cardiac evaluation including echocardiogram (fetal and/or postnatal) in all patients, similar to the evaluation for other patients with diaphragmatic hernia. The possible association between conotruncal CVMs and Fryns syndrome may provide additional support for an etiologic role of genes related to neural crest cell development in the pathogenesis of Fryns syndrome and hence, congenital diaphragmatic hernia.