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.

Different types:

• Filamin A:  FLNA gene (Xq28)

-        loss of function:

1)        periventricular nodular heterotopia or PVNH1 [MIM 300 049]: X-linked autosomal dominant transmission

2) periventricular nodular heterotopia with Ehlers-Danlos syndrome, formerly PVNH4 (or X-linked Ehler-Danlos syndrome) [MIM 300 537]: only in girls, focal epilepsy from adolescence and symptomatology similar to Ehlers Danlos disease (dilatation of aorta, vascular fragility)

3)        periventricular nodular heterotopia with pulmonary emphysema: mostly in girls; multifocal pulmonary emphysema with terminal pulmonary hypertension: indication of pulmonary transplantation

4)        periventricular nodular heterotopia with POIC of neuronal type [MIM 300 048]: chronic intestinal pseudo-obstruction with or without congenital short bowel

5)        FGS2 syndrome (or Opitz-Kaveggia type 2 syndrome) [MIM 305 450]

-  gain of function:

1)  X-linked otopalatatodigital syndromes (1 [MIM 311 300] or 2 [MIM 304 120]), or Taybi syndrome

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). Sometimes associated with signs of X-linked Ehler-Danlos syndrome [MIM 305 200]

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.

• Filamin B :   FLNB gene (3p14)

- 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)

• Filamin C :  FLNC gene (7q32)

- loss of function: one of the causes of the myofibrillar myopathy [MIM 609 524 ](see this term)

- gain of function: distal myopathy

Anesthetic implications: 

epilepsy; chest X-Ray in case of mutation of the filamin A; total blood count; blood platelets transfusion if bleeding, avoid NSAID's.

References : 

-        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.

-        Sasaki E, Byrne AT, Phelan E, Cox DW, Readon W.
A review of filamin A mutations and associated lung disease.
Eur J Pediatr 2019; 178:121-9

-        Burrage LC, Heinle JS, Cerfolio RH, Guillerman RP, Patel KR, Santiago NC, Hoover WC, Mallory GB Jr.
Application of lung volume reduction surgery for a child with filamin A (FLNA) mutations.
Pediatr Pulmonol 2022; 57:224-30

Updated: December 2021