Charcot-Marie-Tooth Disease, axonal, type 2GG(CMT2GG)

MedGen UID:: 1794143
•Concept ID:: C5561933
•: Disease or Syndrome

Synonyms:	Charcot-Marie-Tooth disease dominant intermediate II; Charcot-Marie-Tooth neuropathy, axonal, type 2GG; Charcot-Marie-Tooth neuropathy, type 2GG; CMT2GG
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	GBF1 (10q24.32)

Monarch Initiative:	MONDO:0011675
OMIM®:	606483
Orphanet:	ORPHA100043

Definition

Charcot-Marie-Tooth disease type 2GG (CMT2GG) is an autosomal dominant axonal peripheral neuropathy characterized by slowly progressive distal muscle weakness and atrophy primarily affecting the lower limbs and causing difficulty walking. The onset is usually in adulthood, although rare patients may have mild symptoms from childhood. Some individuals may also have involvement of the hands. Although most patients have hypo- or areflexia at the ankles, distal sensory impairment is not always present, indicating a spectrum of disease encompassing both distal hereditary neuropathy and axonal CMT. Electrophysiologic studies are consistent with a axonal process (summary by Mendoza-Ferreira et al., 2020). For a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210). [from OMIM]

Clinical features

From HPO

Pes cavus

MedGen UID:: 675590
•Concept ID:: C0728829
•: Congenital Abnormality

An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).

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Hammertoe

MedGen UID:: 209712
•Concept ID:: C1136179
•: Anatomical Abnormality

Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.

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Foot dorsiflexor weakness

MedGen UID:: 356163
•Concept ID:: C1866141
•: Finding

Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.

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Dysarthria

MedGen UID:: 8510
•Concept ID:: C0013362
•: Mental or Behavioral Dysfunction

Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.

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Areflexia

MedGen UID:: 115943
•Concept ID:: C0234146
•: Finding

Absence of neurologic reflexes such as the knee-jerk reaction.

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Steppage gait

MedGen UID:: 98105
•Concept ID:: C0427149
•: Finding

An abnormal gait pattern that arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and are unable to dorsiflex and evert the foot. The leg is lifted high on walking so that the toes clear the ground, and there may be a slapping noise when the foot strikes the ground again.

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Hyporeflexia

MedGen UID:: 195967
•Concept ID:: C0700078
•: Finding

Reduction of neurologic reflexes such as the knee-jerk reaction.

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Segmental peripheral demyelination/remyelination

MedGen UID:: 335873
•Concept ID:: C1843077
•: Finding

A segmental pattern of demyelination and regeneration (remyelination) affecting peripheral nerves.

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Distal sensory impairment

MedGen UID:: 335722
•Concept ID:: C1847584
•: Finding

An abnormal reduction in sensation in the distal portions of the extremities.

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Onion bulb formation

MedGen UID:: 376237
•Concept ID:: C1847906
•: Finding

Repeated episodes of segmental demyelination and remyelination lead to the accumulation of supernumerary Schwann cells around axons, which is referred to as onion bulb formation. This finding affects peripheral nerves.

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Motor delay