Femoral‐facial syndrome: A review of the literature and 14 additional patients including a monozygotic discordant twin pair

Abstract

Femoral-facial syndrome (FFS, OMIM 134780), also known as femoral hypoplasia-unusual face syndrome, is a rare sporadic syndrome associated with maternal diabetes, and comprising femoral hypoplasia/agenesis and a distinct facies characterized by micrognathia, cleft palate, and other minor dysmorphisms. The evaluation of 14 unpublished Brazilian patients, prompted us to make an extensive literature review comparing both sets of data. From 120 previously reported individuals with FFS, 66 were excluded due to: not meeting the inclusion criteria (n = 21); not providing sufficient data to ascertain the diagnosis (n = 29); were better assigned to another diagnosis (n = 3); and, being fetuses of the second trimester (n = 13) due to the obvious difficult to confirm a typical facies. Clinical-radiological and family information from 54 typical patients were collected and compared with the 14 new Brazilian patients. The comparison between the two sets of patients did not show any relevant differences. Femoral involvement was most frequently hypoplasia, observed in 91.2% of patients, and the typical facies was characterized by micrognathia (97%), cleft palate (61.8%), and minor dysmorphisms (frontal bossing 63.6%, short nose 91.7%, long philtrum 94.9%, and thin upper lip 92.3%). Clubfoot (55.9%) was commonly observed. Other observed findings may be part of FFS or may be simply concurrent anomalies since maternal diabetes is a common risk factor. While maternal diabetes was the only common feature observed during pregnancy (50.8%), no evidence for a monogenic basis was found. Moreover, a monozygotic discordant twin pair was described reinforcing the absence of a major genetic factor associated with FFS.

Skeletal dysplasias in Latin America

“…BrSD has made important contributions in the literature to the knowledge of SD and dysostosis (Araújo et al, 2016; Barbosa‐Buck et al, 2012; Gomes et al, 2018; Lacarrubba‐Flores et al, 2018; Medina et al, 2020; Silveira et al, 2015; Silveira, Leal, & Cavalcanti, 2016; Silveira, Moreno, & Cavalcanti, 2017). Among these works, three are particularly worthy of mention—the epidemiology of SD (Barbosa‐Buck et al, 2012), the confirmation of the Beemer‐Langer syndrome as a skeletal ciliopathy (Silveira et al, 2017) and the identification of a cluster of Pycnodysostosis in Brazil (Araújo et al, 2016).…”

Biallelic and De Novo Variants in DONSON Reveal a Clinical Spectrum of Cell Cycle‐opathies with Microcephaly, Dwarfism and Skeletal Abnormalities

“…FFS syndrome has been reported in more than 100 patients to date and except for two patients described in the literature, the syndrome was observed to be sporadic. A recent report of sporadic FFS occurring in one of two monozygotic twins would seem to support the potential role of de novo mutations in this condition (Lacarrubba‐Flores et al, ), making FFS another notable exception to the previously described recessive inheritance pattern of most MPDs. These findings suggest that defects in DONSON could lead to both dominant and recessive traits, similar to that reported for several loci, such as EMC1 (OMIM 616875), MAB21L2 (OMIM 615877), ATAD3A (OMIM 617183), and LMNA (OMIM 176670) (Harel et al, ; Harel et al, ; Rainger et al, ; Verstraeten et al, ).…”

The Clinical Manifestations of Femoral-Facial Syndrome in an Orthopaedic Patient

“…Majority of the documented cases report cleft palate, abnormal vertebral size, short limbs, micrognathia and retrognathia, and micromelia (especially concerning the femur) [5,14]. Clinical manifestations reported as somewhat frequent are talipes equinovarus, xoa vara, abnormal fibular morphogenesis with hypoplasia or aplasia, hip dysplasia of the iliac or ischial bones, enlarged obturator foramen, low set ears with microtia and anotia, thin lips and elongated philtrum, upslanted fissures of the eyes, and fused sacrum and coccyx [5,14,15]. The literature also reports very rare findings such as rib fusion, sprengel anomaly, preaxial polydactyly, radioulnar synostosis, or scoliosis [2,5,14], with the latter three present in our case.…”