Prenatal diagnosis of femoral facial syndrome: Three case reports and literature review

• Published in: American journal of medical genetics. Part A Vol. 173; no. 11; pp. 2923 - 2946
• Main Authors: Luisin, Marion, Chevreau, Julien, Klein, Céline, Naepels, Philippe, Demeer, Bénédicte, Mathieu‐Dramard, Michèle, Jedraszak, Guillaume, Gondry‐Jouet, Catherine, Gondry, Jean, Dieux‐Coeslier, Anne, Morin, Gilles
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-11-2017; Wiley
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - diagnostic imaging; Abnormalities, Multiple - genetics; Abnormalities, Multiple - physiopathology; Adult; antenatal diagnosis; Case reports; Cleft Lip - diagnosis; Cleft Lip - diagnostic imaging; Cleft Lip - genetics; Cleft Lip - physiopathology; Cleft lip/palate; Comparative Genomic Hybridization; Diabetes mellitus; Diabetes, Gestational - diagnosis; Diabetes, Gestational - diagnostic imaging; Diabetes, Gestational - physiopathology; Diagnosis; Etiology; facies syndrome; Female; femoral facial syndrome; femoral hypoplasia‐unusual; Femur; Femur - abnormalities; Femur - diagnostic imaging; Femur - physiopathology; Fetus; Fetuses; functional prognosis; Genomes; Humans; Hybridization; Hypoplasia; Infant, Newborn; Intellectual development; Life Sciences; Literature reviews; Male; Middle Aged; Pierre Robin Syndrome - diagnosis; Pierre Robin Syndrome - diagnostic imaging; Pierre Robin Syndrome - genetics; Pierre Robin Syndrome - physiopathology; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal - methods; antenatal diagnosis; femoral facial syndrome; facies syndrome; functional prognosis; femoral hypoplasia-unusual
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.38420

Facial femoral syndrome (FFS) is a rare congenital abnormality, also known as femoral hypoplasia‐unusual facies syndrome, characterized by variable degrees of femoral hypoplasia, associated with specific facial features. Other organ malformations are sometimes present. Most cases are sporadic, but rare family observations suggest genetic origin. However, no chromosomal or genetic abnormalities have ever been incriminated. We conducted a comprehensive literature review and added three new unreported observations. Through these 92 cases, authors aimed to determine sonographic signs that should direct towards diagnosis, and discuss potential genetic etiology. Diagnosis was suspected prenatally in 27.2% of cases, and maternal diabetes was found in 42.4% of patients. When fetal karyotype was available, it was normal in 97.1% of cases, but genomic variations of unknown significance were discovered in all three cases in which array comparative genomic hybridization (CGH) techniques were applied. Femoral affection defining FFS was hypoplasia in 78.3% of cases, agenesis in 12%, and both in 9.8%. Affection was bilateral in 84.8% of cases. Retrognathia was present in 65.2% of cases, cleft lip and/or palate in 63%, and other organ malformations in 53.3%. Intellectual development was normal in 79.2% of cases. Better prenatal recognition of this pathology, notably frequently associated malformations, should lead to a more precise estimation of functional prognosis. It seems likely that today's tendency to systematically employ array‐CGH and exome/genome sequencing methods to investigate malformative sequences will allow the identification of a causal genetic abnormality in the near future.