Cardiovascular, Brain, and Lung Involvement in a Newborn With a Novel FLNA Mutation: A Case Report and Literature Review.

BACKGROUND

Filamin A (FLNA) is an intracellular actin-binding protein, encoded by the FLNA gene, with a wide tissue expression. It is involved in several cellular functions, and extracellular matrix structuring. FLNA gene alterations lead to diseases with a wide phenotypic spectrum, such as brain periventricular nodular heterotopia (PVNH), cardiovascular abnormalities, skeletal dysplasia, and lung involvement.

CLINICAL FINDINGS

We present the case of a female infant who showed at birth aortic valve stenosis and PVNH, and subsequently developed interstitial lung disease with severe pulmonary hypertension.

PRIMARY DIAGNOSIS

The association of aortic valve dysplasia, left ventricular outflow obstruction, persistent patent ductus arteriosus, and brain heterotopic gray matter suggested a possible FLNA gene alteration. A novel heterozygous intronic variant in the FLNA gene (NM_001110556.1), c.4304-1G >A, was detected.

INTERVENTIONS

In consideration of valve morphology and severity of stenosis, the neonate was scheduled for a transcatheter aortic valvuloplasty. At 3 months of life, she developed hypoxemic respiratory failure with evidence of severe pulmonary hypertension. Inhaled nitric oxide (iNO) and milrinone on continuous infusion were started. Because of a partial response to iNO, an intravenous continuous infusion of sildenafil was introduced.

OUTCOMES

In consideration of severe clinical course and fatal outcome, the new FLNA gene mutation described in our patient seems to be associated with a loss of function of FLNA.

PRACTICE RECOMMENDATIONS

Lung and brain involvement, in association with left ventricular outflow obstruction and persistent patency of ductus arteriosus, should be considered highly suggestive of FLNA gene alterations, in a female newborn.