Fontaine–Farriaux syndrome: A recognizable craniosynostosis syndrome with nail, skeletal, abdominal, and central nervous system anomalies

Abstract

Craniosynostosis is an etiologically heterogeneous malformation, which may present as an isolated finding or in association with other anomalies. The concurrence of craniosynostosis together with specific central nervous system, abdominal, genital, and limb malformations defines the Fontaine-Farriaux syndrome, described so far in only two patients. We report on a stillborn who mainly presented severe intrauterine growth retardation, bilateral coronal synostosis, generalized nail hypo/aplasia more evident on the posterior side, tapered digits, mild cutaneous syndactyly, abdominal muscle hypoplasia, micropenis and bilateral cryptorchidism. Skeletal radiographs revealed universal platyspondyly and necropsy findings comprised intestinal malrotation, abnormal cortical gyral formation, periventricular heterotopia, and cerebellar hypoplasia. Comparison between the present and the two previously described patients demonstrates that our case shows a combination of features strikingly resembling the original description. Conversely, the second reported patient shows a very atypical phenotype and is, most probably, affected by a distinct clinical entity. The triad of craniosynostosis, anonychia, and abdominal muscle hypo/aplasia emerges as the most consistent core phenotype, although skeletal and brain anomalies are relevant ancillary findings. An in-depth differential diagnosis with other partially overlapping conditions is carried out.

A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopia

“…With the recognition that this condition and FFS could be allelic, if not the same entity, the patient studied here can now no longer be regarded as an example of FFS. The reasoning underlying this contention is that he never manifested anonychia, abdominal wall hypoplasia or death in infancy, all features observed in the other two cases of FFS [Fontaine et al, 1977;Castori et al, 2009]. The genetic aetiology of FFS therefore remains to be elucidated and for the reasons stated above the microdeletion described here does not advance knowledge in this respect.…”

A progeroid syndrome with neonatal presentation and long survival maps to 19p13.3p13.2

“…In several other syndromes, the progeroid phenotype is usually seen at birth. Examples of the latter group include Wiedemann-Rautenstrauch syndrome (WRS; MIM 264090), Petty-Laxova-Wiedemann syndrome (PLWS; MIM 612289), Fontaine-Farriaux syndrome (Castori et al, 2009), Hallerman-Strief syndrome (MIM 234100), and De Barsy syndrome (MIM 219150). Other conditions with neonatal presentation include cutis laxa type 1A (MIM 219100), cutis laxa type IIB (MIM 612940) (Al-Gazali and Ali, 2010), geroderma osteodysplastica (MIM 231070), and some forms of Marfan syndrome (Graul-Neumann et al, 2010;Goldblatt et al, 2011).…”

De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise

“…Fontaine syndrome is an infrequently described human progeroid syndrome characterized by prenatal and postnatal growth retardation, decreased subcutaneous fat tissue, sparse hair, a triangular face, a widely open anterior fontanel, craniosynostosis (in some), a convex and broad nasal ridge, micrognathia, small distal phalanges of the fingers and toes, and early death (in most). [6][7][8][9][10][11][12][13] It was first reported by Fontaine et al in 1977, 6 so we suggest naming the entity Fontaine syndrome. It is likely to be the same entity as described by Petty et al 7 (Petty-type congenital progeroid syndrome [MIM: 612289]).…”

“…Individuals originated from Slovenia, France, Spain, and Italy. Individual 1 is described in detail in the Supplemental Note, and individuals 2, 9 3, 8 and 4 12 have been published before. All presented with prenatal and postnatal growth retardation; an aged appearance characterized by decreased subcutaneous fat, wrinkled skin, and prominent veins; a large anterior fontanel, an abnormal scalp hair pattern, similar facial dysmorphisms (e.g., triangular face, convex nasal ridge, and low-set ears), and small nails and distal phalanges, especially on the ulnar and fibular sides.…”