MedGen

The phenotypic spectrum of GARS1-associated axonal neuropathy ranges from GARS1 infantile-onset SMA (GARS1-iSMA) to GARS1 adolescent- or early adult-onset hereditary motor/sensory neuropathy (GARS1-HMSN). GARS1-iSMA. Age of onset ranges from the neonatal period to the toddler years. Initial manifestations are typically respiratory distress, poor feeding, and muscle weakness (distal greater than proximal). Weakness is slowly progressive, ultimately requiring mechanical ventilation and feeding via gastrostomy tube. GARS1-HMSN. Age of onset is most commonly during the second decade (range eight to 36 years). Initial manifestations are typically muscle weakness in the hands sometimes with sensory deficits. Lower limb involvement (seen in ~50% of individuals) ranges from weakness and atrophy of the extensor digitorum brevis and weakness of toe dorsiflexors to classic peroneal muscular atrophy with foot drop and a high steppage gait. [from GeneReviews]

The phenotypic spectrum of GARS1-associated axonal neuropathy ranges from GARS1 infantile-onset SMA (GARS1-iSMA) to GARS1 adolescent- or early adult-onset hereditary motor/sensory neuropathy (GARS1-HMSN). GARS1-iSMA. Age of onset ranges from the neonatal period to the toddler years. Initial manifestations are typically respiratory distress, poor feeding, and muscle weakness (distal greater than proximal). Weakness is slowly progressive, ultimately requiring mechanical ventilation and feeding via gastrostomy tube. GARS1-HMSN. Age of onset is most commonly during the second decade (range eight to 36 years). Initial manifestations are typically muscle weakness in the hands sometimes with sensory deficits. Lower limb involvement (seen in ~50% of individuals) ranges from weakness and atrophy of the extensor digitorum brevis and weakness of toe dorsiflexors to classic peroneal muscular atrophy with foot drop and a high steppage gait. [from GeneReviews]

The spectrum of BSCL2-related neurologic disorders includes Silver syndrome and variants of Charcot-Marie-Tooth neuropathy type 2, distal hereditary motor neuropathy (dHMN) type V, and spastic paraplegia 17. Features of these disorders include onset of symptoms ranging from the first to the seventh decade, slow disease progression, upper motor neuron involvement (gait disturbance with pyramidal signs ranging from mild to severe spasticity with hyperreflexia in the lower limbs and variable extensor plantar responses), lower motor neuron involvement (amyotrophy of the peroneal muscles and small muscles of the hand), and pes cavus and other foot deformities. Disease severity is variable among and within families. [from GeneReviews]

Axonal Charcot-Marie-Tooth disease type 2HH (CMT2HH) is an autosomal dominant peripheral neuropathy characterized predominantly by onset of vocal cord weakness resulting in stridor in infancy or early childhood. The vocal cord paresis remains throughout life and may be severe enough to require tracheostomy. Additional features of the disorder usually include pes cavus and scoliosis. Some patients have mild distal muscle weakness and atrophy primarily affecting the lower limbs, although the upper limbs may also be involved, and distal sensory impairment, often with hyporeflexia (Sullivan et al., 2020). For a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210). [from OMIM]

A complex hereditary spastic paraplegia with characteristics of mild to severe lower limbs spasticity, hyperreflexia, extensor plantar responses, pes cavus and significant wasting and weakness of the small hand muscles. Impaired vibration sensation, temporal lobe epilepsy and cognitive dysfunction were also reported. [from SNOMEDCT_US]