Floppy infant syndrome due to spectrinopathies by SPTBN4 gene

*Correspondence: [e-mail].

Abstract

Case Presentation: H.S.S., female, eleven months old, first evaluated by child neurology at eight months of age for hypotonia. No parental consanguinity, maternal history of treated gestational syphilis, without other pregnancy or delivery complications nor medical antecedents. At three months of age, difficulty in head control and weight gain was noted. At the initial evaluation, she was malnourished, with almond-shaped eyes, carpal mouth, ogival palate, and bell-shaped thorax. Neurological examination revealed good interaction, global hypotonia, hypotrophy, weakness and areflexia, with tongue myofasciculations. Hospitalization was decided for nutritional evaluation and diagnostic research. Oral feeding was discontinued, gastrostomy indicated, with no respiratory assistance needed. Cranial tomography, brain magnetic resonance imaging and muscle enzymes were normal. Electroneuromyography was suggestive of chronic peripheral preganglionic/neurogenic motor involvement affecting the four limbs. Molecular panel for neuromuscular diseases showed a pathogenic variant c.2147delA; p.Gln716Argfs*27 in homozygosis in SPTBN4 gene. The patient was discharged from hospital and continues in multidisciplinary outpatient follow-up and rehabilitation.

Discussion: Spectrins are proteins with support function that bind the plasma membrane to cytoskeletal actin. The SPTBN4 gene encodes the non-erythrocyte beta spectrin 4, a protein required for the clustering of ion channels in the initial segments of axons and in nodes of Ranvier, axonal domains important for the initiation, propagation of modulation of action potentials. SPTBN4 gene-associated disorder has autosomal recessive inheritance and presents with severe developmental delay and/or intellectual disability, congenital hypotonia, weakness, hyporeflexia/areflexia, indicative of neuropathy, and dysphagia. Epilepsy, cortical visual impairment and sensorineural deafness may also be present. The variant found in the patient has not been previously described in scientific literature.

Final Comments: Facing a hypotonic infant, it is important to identify the topographic diagnosis by neurological examination and complementary tests. Genetic analysis by next-generation sequencing is essential for definitive diagnosis and genetic counseling. Spectrinopathies present with axonal motor neuropathy/neuronopathy and should be considered in the differential diagnosis of neuromuscular causes of floppy infant.

Publication History

Article published online:
12 May 2025