Group of diseases due to a mutation in genes that code for the synthesis of filamin A, B, or C. Filamins are proteins that fix on the actin to stabilize its three-dimensional structure. They have a role in cell signaling and in embryogenesis.
- loss of function:
2) periventricular nodular heterotopia with Ehlers-Danlos syndrome [MIM 300 537]: only in girls, focal epilepsy from adolescence and symptomatology of Ehlers Danlos disease (dilatation of aorta, vascular fragility)
3) periventricular nodular heterotopia with POIC of neuronal type (chronic intestinal pseudo-obstruction) or pulmonary emphysema or diaphragmatic hernia
- gain of function:
2) Melnick-Needles syndrome (see this term), [MIM 309 350]
3) fronto-metaphyseal dysplasia, or Gorlin-Cohen syndrome [MIM 305 620, 617 137]; sclerosis of the base of the skull and hypoplasia of the distal phalanges, with progressive contractures of the hands, elbows, knees and ankles, persisting beyond the first two decades. Moderate but progressive scoliosis; curved limbs and campomelia are also observed. Facial dysmorphism: supraorbital hyperostosis, downward and outside sliding palpebral fissures, hypertelorism, broad nasal edge and tip, hypodontia, oligodontia and sometimes craniosynostosis. Conduction and sensorineural hearing loss. Extra-skeletal signs: congenital heart defect (ASD, VSD, pulmonary artery stenosis, aortic dilation), congenital subglottic stenosis; underdeveloped muscles, especially around the scapular belt and intrinsic muscles of the hand (common). Ureteral or urethral obstruction
4) congenital valvular dysplasia [MIM 314 400]: thickening of cardiac valves without any cerebral or skeletal involvement, but other causes are possible (trisomy 21, Marfan, Noonan etc)
5) terminal bone dysplasia - defects of pigmentation [MIM 300 244]: only in girls (lethal for boys). Digital fibromatosis (rapidly growing small fibromas with spontaneous involution), depigmentation spots at the level of the face, frenulum in the mouth, joint contractures and pterygium, brachy - and camptodactyly, short arched limbs
Some patients with a mutation of filamin A present with thrombocytopenia as the intraplatelet filamin A get linked to actin filaments through the GPIα.
- loss of function: spondylo-carpo-tarsal syndrome: fusion of some vertebrae, bones of the carpus and the tarsus
- gain of function: Larsen syndrome, atelosteogenesis syndromes (1 or 3) (see these terms)
- loss of function: one of the causes of the myofibrillar myopathy [MIM 609 524 ](see this term)
- gain of function: distal myopathy
total blood count; blood platelets transfusion if bleeding, avoid NSAID's.
- Boutroux H, Favier R, Héritier S, Lapillone H, Ballerini P, Leverger G.
Mise au point : les thrombopénies constitutionnelles.
J Pediatrie et Puériculture 2018 ; 31 : 160-7.
Updated: December 2020