Charcot-marie-tooth disease, axonal, type 2DD(CMT2DD)

MedGen UID:: 1648475
•Concept ID:: C4747974
•: Disease or Syndrome

Synonym:	CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2DD
SNOMED CT:	Autosomal dominant Charcot-Marie-Tooth disease type 2DD (1187620007); ATP1A1-related autosomal dominant Charcot-Marie-Tooth disease type 2 (1187620007); ATP1A1 (ATPase Na+/K+ transporting subunit alpha 1) related autosomal dominant Charcot-Marie-Tooth disease type 2 (1187620007)
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.	ATP1A1 (1p13.1)

Monarch Initiative:	MONDO:0054833
OMIM®:	618036
Orphanet:	ORPHA521414

Definition

Charcot-Marie-Tooth disease type 2DD is an autosomal dominant peripheral sensorimotor neuropathy mainly affecting the lower limbs. Affected individuals have gait impairment due to distal muscle weakness and atrophy. Some patients may also have involvement of the distal upper limbs, resulting in atrophy of the intrinsic hand muscles. The age at onset and severity of the disorder is highly variable, even within families, and those with earlier onset in late childhood or the teenage years tend to have a more severe disease course. Patients remain ambulatory even late in the disease, although some may require orthotic devices (summary by Lassuthova et al., 2018). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A (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).

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Areflexia

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

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

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Hyporeflexia