Tall Stature-Intellectual Disability-Renal Anomalies Syndrome
A rare overgrowth syndrome associated with multiple congenital anomalies characterized by tall stature, large hands and feet with large thumbs and halluces, spatulate digits, developmental delay and facial dysmorphism.
Epidemiology
To date only 4 cases from 2 families have been reported in the literature.
Clinical description
The overgrowth disorder is characterized by tall stature, large hands and feet with large thumbs/halluces. Facial features include round face with widely spaced and deep-set eyes, epicanthal folds, flat midface, long and downslanting palpebral fissures, large prominent ears, thick lips, macroglossia. Patients exhibit developmental delay. Intellect ranges from norrmal with learning difficulties to intellectual disability. A range of variable congenital anomalies have been reported and include ocular defects (retinal coloboma or refraction errors), cardiac anomalies (ventricular septal defect, mitral valve prolapse, double chamber right ventricle), kidney malformations (renal malrotation with left bifid ureter, nephromegaly, cystic dysplastic kidneys), connective tissue disorders (inguinal hernia), as well as orthopedic features (talipes equinovarus, internal rotation of the femurs and tibias, bowing of the legs, and spina bifida occulta). Other features may include early-onset varicose veins, transient or chronic benign neutropenia (with normal bone marrow examination), sensorineural hearing loss and Wilms tumor (one patient).
Etiology
Biallelic loss of function variants in FIBP (11q13.1) are responsible for this phenotype.
Diagnostic methods
Diagnosis is with next generation sequencing (exome, genome or panel for developmental disorders).
Differential diagnosis
Differential diagnosis includes other overgrowth disorders, such as Beckwith-Wiedeman syndrome or Simpson-Golabi-Behmel syndrome in the association with tall stature, nephromegaly, macroglossia, predisposition to Wilms tumor.
Antenatal diagnosis
Prenatal diagnosis can be proposed to parents with an affected child.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child at each pregnancy.
Management and treatment
Management is multidisciplinary and depends on the particular manifestations and may include ophthalmological, cardiac, hematological and orthopedic evaluation and follow-up. Social care requirements for learning disability should be assessed. Psychiatric symptoms should be evaluated, in particular in adulthood. Hearing evaluations are required with possible prescription for hearing aids. Surgery may be recommended in cases of inguinal hernia and early-onset varicose veins. Follow-up for Wilms tumor with kidney ultrasound every 3 months from diagnosis to 8-years-old is recommended.
Prognosis
The possible lethality of the disorder has been questioned because of an increased occurrence of stillbirths and miscarriage in one family. A predisposition for Wilms tumor is suspected. Neutropenia does not seem associated with recurrent infections.