Femoral-facial syndrome: Report of 2 fetal cases

Abstract

Femoral-facial syndrome (FFS) is a congenital disorder, characterized by facial dysmorphism and femoral hypoplasia. We describe the prenatal ultrasound and autopsy findings of FFS in 2 female fetuses born to diabetic mothers. Prenatal ultrasound showed micrognathia, low-set dysplastic ears and very short femora. Autopsy also demonstrated cleft palate, hypoplastic genitalia and visceral malformations including interventricular communication and posthemorrhagic hydrocephalus. Histologic study showed hyperplasia of the islets of Langerhans and femoral cartilage abnormalities. The growth plate displayed poor columnar organization of the growth plate with small zones of chondrocyte hypertrophy. Our case reports and the previously published cases of FFS allow discussing the variable expression of this challenging condition, its strong association with maternal diabetes mellitus and the main differential diagnoses.

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

“…Johnson et al [5] expand the diagnostic criteria so that, for a diagnosis of FFS to be made, femoral hypoplasia along with two out of the four facial features must be present: long philtrum with thin lip, mandible/mouth hypoplasia, upslanting palpebral fissures, or undeveloped nasal alae. When describing the femoral hypoplasia, Darouich et al describe that it had been reported as symmetric in females, as in our case, but asymmetric in males [2]. 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.…”

“…Other system clinical manifestations can include cardiovascular, neurological, or genitourinary with features such as enlarged penis, ventriculomegaly, polycystic kidney dysplasia, or renal hypoplasia [16]. While genitourinary anomalies are most commonly documented, accounting for 53% of cases, neurological manifestations that impact neural migration may explain the intellectual disability present in 80% of cases [2,5]. Notably, FFS and caudal regression syndrome are both associated with maternal diabetes and share several similar clinical manifestations [17,18].…”

“…Femoral-facial syndrome is a rare disorder first described by Daentl et al in 1975 [1]. Though its formal name has fluctuated since its inception, it was first characterized as "femoral hypoplasia unusual-facies syndrome" with fewer than 70 cases in the current literature to the best of our knowledge [2]. The full syndrome encompasses a wide variety of systems giving this congenital disorder significant clinical heterogeneity.…”

First Reported Case of Femoral Facial Syndrome in an Adult: Esophageal Adenocarcinoma as a Progressive Gastrointestinal Manifestation

“…These criteria are essential to help differentiate FFS from other similarly presenting conditions such as caudal dysplasia syndrome [ 1 , 2 , 6 - 8 ]. Literature on FFS is limited with approximately 70 reported cases worldwide, affecting African American, Arab, Caucasian, and Chinese populations as of 2021 [ 1 , 3 , 4 , 6 , 9 ]. Research has focused on orthopedic management and detection of FFS in utero and cases have mainly been documented in neonates, infants, and, rarely, toddlers [ 3 - 7 , 10 , 11 ].…”