Thauvin-Robinet-Faivre Syndrome

A number sign (#) is used with this entry because of evidence that Thauvin-Robinet-Faivre syndrome (TROFAS) is caused by homozygous mutation in the FIBP gene (608296) on chromosome 11q13.

Description

Thauvin-Robinet-Faivre syndrome is an autosomal recessive disorder characterized by generalized overgrowth, mainly of height, and mildly delayed psychomotor development with mild or severe learning difficulties. More variable features may include congenital heart defects, kidney abnormalities, and skeletal defects. Patients may have an increased risk for Wilms tumor (summary by Akawi et al., 2016).

Clinical Features

Thauvin-Robinet et al. (2016) reported a 23-year-old man, born of consanguineous North African parents, with an overgrowth syndrome and severe learning disabilities. He was born at term with macrosomia and macrocephaly, and the overgrowth persisted throughout childhood. He had developmental delay with language disabilities. Additional features included retinal coloboma, ventricular septal defect, mitral valve prolapse, renal malrotation with left bifid ureter, and transient neutropenia. At age 21, he had surgery for inguinal hernia and severe varicose veins. Dysmorphic facial features included long and downslanting palpebral fissures, large prominent ears, thick lips, and macroglossia. He had large hands and feet with large thumbs and halluces. Brain imaging and cardiac function were normal.

Akawi et al. (2016) reported 3 sibs, born of consanguineous Arab parents, with an overgrowth syndrome associated with mildly delayed developmental milestones and intellectual disability. The sibs were 14, 10, and 3 years of age. Common features included tall stature and mild dysmorphic facial features, such as round face with widely spaced and deep-set eyes, epicanthal folds, flat midface, and full lips. Additional abnormalities were variable. The oldest sib had ventricular septal defect, double chamber right ventricle, sensorineural hearing loss, and astigmatism. She developed a Wilms tumor at age 4 years. The middle child had several skeletal abnormalities, including talipes equinovarus, internal rotation of the femurs and tibias, bowing of the legs, and spina bifida occulta. The youngest child had nephromegaly with cystic dysplastic kidneys and a nonfunctioning right kidney. The 2 older sibs had chronic benign neutropenia with normal bone marrow examination. There was a family history of 3 miscarriages and 3 stillbirths.

Inheritance

The transmission pattern of TROFAS in the family reported by Akawi et al. (2016) was consistent with autosomal recessive inheritance.

Molecular Genetics

In a 23-year-old man, born of consanguineous North African parents, with TROFAS, Thauvin-Robinet et al. (2016) identified a homozygous nonsense mutation in the FIBP gene (Q218X; 608296.0001). The mutation, which was found by exome sequencing, segregated with the disorder in the family. Patient fibroblasts showed excessive proliferation compared to controls.

In 3 sibs, born of consanguineous Arab parents, with TROFAS, Akawi et al. (2016) identified a homozygous mutation in the FIBP gene (608296.0002). Patient fibroblasts showed increased cellular proliferation compared to controls.