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Charcot-Marie-Tooth disease dominant intermediate F(CMTDIF)

MedGen UID:: 1666273
•Concept ID:: C4749463
•: Disease or Syndrome

Synonyms:	CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE F; CMTDIF
SNOMED CT:	Autosomal dominant intermediate Charcot-Marie-Tooth disease type F (770759001)
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.	GNB4 (3q26.33)

Monarch Initiative:	MONDO:0014074
OMIM®:	615185
Orphanet:	ORPHA352670

Definition

CMTDIF is an autosomal dominant neurologic disorder characterized by onset around adolescence of slowly progressive distal muscle atrophy and weakness affecting the upper and lower limbs and resulting in steppage gait. There is distal sensory impairment with decreased reflexes. Nerve conduction velocities are variable, ranging from the demyelinating to the axonal range (summary by Soong et al., 2013). For a discussion of genetic heterogeneity of CMTDI, see 606482. [from OMIM]

Clinical features

From HPO

Absent patellar reflexes

MedGen UID:: 643630
•Concept ID:: C0558844
•: Finding

Absence of the knee jerk reflex, which can normally be elicited by tapping the patellar tendon with a reflex hammer just below the patella.

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Absent Achilles reflex

MedGen UID:: 108240
•Concept ID:: C0558845
•: Finding

Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.

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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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Distal lower limb muscle weakness

MedGen UID:: 324514
•Concept ID:: C1836450
•: Finding

Reduced strength of the distal musculature of the legs.

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Distal upper limb muscle weakness

MedGen UID:: 461970
•Concept ID:: C3150620
•: Finding

Reduced strength of the distal musculature of the arms.

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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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Peripheral demyelination

MedGen UID:: 451074
•Concept ID:: C0878575
•: Pathologic Function

A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.

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Impaired vibratory sensation

MedGen UID:: 220959
•Concept ID:: C1295585
•: Finding

A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient.

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Impaired pain sensation

MedGen UID:: 373348
•Concept ID:: C1837522
•: Finding

Reduced ability to perceive painful stimuli.

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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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Axonal regeneration

MedGen UID:: 340241
•Concept ID:: C1854454
•: Finding

The presence of axonal regeneration following a previous axonal lesion.

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Distal lower limb amyotrophy

MedGen UID:: 324515
•Concept ID:: C1836451
•: Disease or Syndrome

Muscular atrophy of distal leg muscles.

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Distal upper limb amyotrophy

MedGen UID:: 867223
•Concept ID:: C4021581
•: Disease or Syndrome

Muscular atrophy of distal arm muscles.

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Abnormality of limbs
Abnormality of the musculoskeletal system
- Distal lower limb amyotrophy
- Distal upper limb amyotrophy
Abnormality of the nervous system

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVCharcot-Marie-Tooth disease

Autosomal dominant intermediate Charcot-Marie-Tooth disease
- Charcot-Marie-Tooth disease dominant intermediate F

Recent clinical studies

Diagnosis

A novel missense variant (Gln220Arg) of GNB4 encoding guanine nucleotide-binding protein, subunit beta-4 in a Japanese family with autosomal dominant motor and sensory neuropathy.

Miura S, Morikawa T, Fujioka R, Noda K, Kosaka K, Taniwaki T, Shibata H
Eur J Med Genet 2017 Sep;60(9):474-478. Epub 2017 Jun 19 doi: 10.1016/j.ejmg.2017.06.006. PMID: 28642160

A novel mutation in the dynamin 2 gene in a Charcot-Marie-Tooth type 2 patient: clinical and pathological findings.

Bitoun M, Stojkovic T, Prudhon B, Maurage CA, Latour P, Vermersch P, Guicheney P
Neuromuscul Disord 2008 Apr;18(4):334-8. Epub 2008 Apr 3 doi: 10.1016/j.nmd.2008.01.005. PMID: 18394888

See all (2)

Clinical prediction guides

A novel missense variant (Gln220Arg) of GNB4 encoding guanine nucleotide-binding protein, subunit beta-4 in a Japanese family with autosomal dominant motor and sensory neuropathy.

Miura S, Morikawa T, Fujioka R, Noda K, Kosaka K, Taniwaki T, Shibata H
Eur J Med Genet 2017 Sep;60(9):474-478. Epub 2017 Jun 19 doi: 10.1016/j.ejmg.2017.06.006. PMID: 28642160

See all (1)

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Charcot-Marie-Tooth disease dominant intermediate F(CMTDIF)

Definition

Clinical features

Term Hierarchy

Recent clinical studies

Diagnosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Molecular resources

Consumer resources

Reviews

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