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  • CN375538 has been replaced by C5882697, showing C5882697

Neuronopathy, distal hereditary motor, autosomal dominant 11(DHMN11; HMND11)

MedGen UID:
1849676
Concept ID:
C5882697
Disease or Syndrome
Synonym: NEUROPATHY, DISTAL HEREDITARY MOTOR, 11
 
Gene (location): SPTAN1 (9q34.11)
 
Monarch Initiative: MONDO:0957875
OMIM®: 620528

Definition

Autosomal dominant distal hereditary motor neuronopathy-11 (HMND11) is a peripheral axonal motor neuropathy characterized by juvenile or young-adult onset of distal limb muscle weakness and atrophy mainly affecting the lower limbs, resulting in gait instability and walking difficulties. Foot deformities may also be present. The disorder is usually slowly progressive, and patients remain ambulatory until late adulthood. Some affected individuals may have distal upper limb and hand involvement or mild distal sensory abnormalities, but motor symptoms dominate the clinical picture. Electrophysiologic studies are consistent with a length-dependent axonal motor or sensorimotor neuropathy. Seizures are not present and brain imaging is normal (Beijer et al., 2019). One reported affected individual had a marfanoid habitus and mild speech delay with learning disabilities, suggesting possible expansion of the phenotypic spectrum (Ylikallio et al., 2020). For a discussion of genetic heterogeneity of autosomal dominant distal HMN, see HMND1 (182960). [from OMIM]

Clinical features

From HPO
Asthenia
MedGen UID:
2107
Concept ID:
C0004093
Sign or Symptom
A state characterized by a feeling of weakness and loss of strength leading to a generalized weakness of the body.
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Hallux valgus
MedGen UID:
5416
Concept ID:
C0018536
Anatomical Abnormality
Lateral deviation of the great toe (i.e., in the direction of the little toe).
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).
Hammertoe
MedGen UID:
209712
Concept ID:
C1136179
Anatomical Abnormality
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
Upper limb muscle weakness
MedGen UID:
305607
Concept ID:
C1698196
Finding
Weakness of the muscles of the arms.
Hyporeflexia of lower limbs
MedGen UID:
371881
Concept ID:
C1834696
Finding
Reduced intensity of muscle tendon reflexes in the lower limbs. Reflexes are elicited by stretching the tendon of a muscle, e.g., by tapping.
Distal lower limb muscle weakness
MedGen UID:
324514
Concept ID:
C1836450
Finding
Reduced strength of the distal musculature of the legs.
Hyporeflexia of upper limbs
MedGen UID:
323007
Concept ID:
C1836835
Finding
Reduced intensity of muscle tendon reflexes in the upper limbs. Reflexes are elicited by stretching the tendon of a muscle, e.g., by tapping.
Areflexia of lower limbs
MedGen UID:
347285
Concept ID:
C1856694
Finding
Inability to elicit tendon reflexes in the lower limbs.
Long fingers
MedGen UID:
346836
Concept ID:
C1858091
Finding
The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand.
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.
Areflexia of upper limbs
MedGen UID:
388832
Concept ID:
C2674177
Finding
Inability to elicit tendon reflexes in the upper limbs.
Tall stature
MedGen UID:
69137
Concept ID:
C0241240
Finding
A height above that which is expected according to age and gender norms.
Hypoesthesia
MedGen UID:
6974
Concept ID:
C0020580
Finding
Decreased ability to perceive touch.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Restless legs
MedGen UID:
48427
Concept ID:
C0035258
Disease or Syndrome
Restless Leg Syndrome (RLS) is a condition characterized by an uncomfortable and restless sensation in the legs that occurs after going to bed, often leading to insomnia.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Clumsiness
MedGen UID:
66690
Concept ID:
C0233844
Sign or Symptom
Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects.
Hyperactive patellar reflex
MedGen UID:
66003
Concept ID:
C0240116
Finding
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.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Dyslexia
MedGen UID:
96906
Concept ID:
C0476254
Mental or Behavioral Dysfunction
A learning disorder characterized primarily by difficulties in learning to read and spell. Dyslectic children also exhibit a tendency to read words from right to left and to confuse letters such as b and d whose orientation is important for their identification. Children with dyslexia appear to be impaired in phonemic skills (the ability to associate visual symbols with the sounds they represent).
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Broad-based gait
MedGen UID:
167799
Concept ID:
C0856863
Finding
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
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.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Motor axonal neuropathy
MedGen UID:
413108
Concept ID:
C2749625
Disease or Syndrome
Progressive impairment of function of motor axons with muscle weakness, atrophy, and cramps. The deficits are length-dependent, meaning that muscles innervated by the longest nerves are affected first, so that for instance the arms are affected at a later age than the onset of deficits involving the lower leg.
Decreased compound muscle action potential amplitude
MedGen UID:
908357
Concept ID:
C4230625
Finding
Reduced level of the compound muscle action potential (CMAP), which is recorded following electrical stimulation of a nerve from surface electrodes overlying a muscle supplied by that nerve.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Difficulty climbing stairs
MedGen UID:
68676
Concept ID:
C0239067
Finding
Reduced ability to climb stairs.
Achilles tendon contracture
MedGen UID:
98052
Concept ID:
C0410264
Anatomical Abnormality
A contracture of the Achilles tendon.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Frequent falls
MedGen UID:
163408
Concept ID:
C0850703
Finding
Distal lower limb amyotrophy
MedGen UID:
324515
Concept ID:
C1836451
Disease or Syndrome
Muscular atrophy of distal leg muscles.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Upper limb amyotrophy
MedGen UID:
867165
Concept ID:
C4021523
Disease or Syndrome
Muscular atrophy involving the muscles of the upper limbs.
Claw hand deformity
MedGen UID:
1814631
Concept ID:
C5702555
Anatomical Abnormality
An abnormality of the hand characterized by metacarpophalangeal (MCP) hyperextension and proximal interphalangeal (PIP) and distal interphalangeal (DIP) flexion. The position of the affected hand is said to resemble a claw.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Narrow palate
MedGen UID:
278045
Concept ID:
C1398312
Finding
Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective).

Recent clinical studies

Etiology

Akçimen F, Vural A, Durmuş H, Çakar A, Houlden H, Parman YG, Nazlı Başak A
J Hum Genet 2019 Nov;64(11):1141-1144. Epub 2019 Aug 17 doi: 10.1038/s10038-019-0652-y. PMID: 31420593

Clinical prediction guides

Passamonti L, Muglia M, Magariello A, Bellesi M, Conforti FL, Mazzei R, Patitucci A, Gabriele AL, Sprovieri T, Peluso G, Caracciolo M, Medici E, Logullo F, Provinciali L, Quattrone A
Neuromuscul Disord 2004 Nov;14(11):705-10. doi: 10.1016/j.nmd.2004.07.004. PMID: 15482954

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