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Neuropathy, congenital hypomyelinating, 2(CHN2)

MedGen UID:
1648446
Concept ID:
C4722277
Disease or Syndrome
Synonyms: CHN2; NEUROPATHY, CONGENITAL HYPOMYELINATING, 2
 
Gene (location): MPZ (1q23.3)
 
Monarch Initiative: MONDO:0020765
OMIM®: 618184

Definition

Congenital hypomyelinating neuropathy-2 is an autosomal dominant neurologic disorder characterized by early-onset hypotonia, severely delayed motor development, muscle weakness with areflexia, and severely decreased nerve conduction velocities (NCV) resulting from improper myelination of axons. The severity is variable: some patients may present at birth with contractures and respiratory insufficiency, whereas others may achieve walking (summary by Warner et al., 1996). CHN shows significant phenotypic overlap with Dejerine-Sottas syndrome (DSS; 145900), which is also a neuropathy with early onset. Some classify the disorders differently, noting that CHN is characterized by hypo- or amyelination resulting from a congenital defect in myelin formation, whereas DSS has features of continuous myelin breakdown, with demyelination and remyelination (summary by Smit et al., 2008). For a discussion of genetic heterogeneity of CHN, see CHN1 (605253). [from OMIM]

Clinical features

From HPO
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.
Hypokinesia
MedGen UID:
39223
Concept ID:
C0086439
Finding
Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Sensory ataxia
MedGen UID:
66020
Concept ID:
C0240991
Sign or Symptom
Incoordination of movement caused by a deficit in the sensory nervous system. Sensory ataxia can be distinguished from cerebellar ataxia by asking the patient to close his or her eyes. Persons with cerebellar ataxia show only a minimal worsening of symptoms, whereas persons with sensory ataxia show a marked worsening of symptoms.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Persistent head lag
MedGen UID:
256151
Concept ID:
C1141883
Finding
The Premie-Neuro and the Dubowitz Neurological Examination score head lag in the same manner. Scoring for both is as follows
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.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Decreased number of peripheral myelinated nerve fibers
MedGen UID:
346872
Concept ID:
C1858285
Finding
A loss of myelinated nerve fibers in the peripheral nervous system (in general, this finding can be observed on nerve biopsy).
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Delayed ability to stand
MedGen UID:
1370611
Concept ID:
C4476709
Finding
A failure to achieve the ability to stand up at an appropriate developmental stage. Most children begin to walk alone at 11 to 15 months of age. On average, children can stand while holding on at the age of 9 to 10 months, can pull up to stand and walk with one hand being held at 12 months, and can stand alone and walk well at 18 months.
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.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Facial diplegia
MedGen UID:
322796
Concept ID:
C1836003
Finding
Facial diplegia refers to bilateral facial palsy (bilateral facial palsy is much rarer than unilateral facial palsy).
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.
Severe muscular hypotonia
MedGen UID:
326544
Concept ID:
C1839630
Finding
A severe degree of muscular hypotonia characterized by markedly reduced muscle tone.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Diagnosis

Madrid RE, Lofgren A, Baets J, Timmerman V
Neuromuscul Disord 2013 Apr;23(4):345-8. Epub 2013 Jan 10 doi: 10.1016/j.nmd.2012.12.005. PMID: 23313019
Hui-Chou HG, Hashemi SS, Hoke A, Dellon AL
J Reconstr Microsurg 2011 Jan;27(1):67-74. Epub 2010 Oct 25 doi: 10.1055/s-0030-1267832. PMID: 20976668

Clinical prediction guides

Jouaud M, Gonnaud PM, Richard L, Latour P, Ollagnon-Roman E, Sturtz F, Mathis S, Magy L, Vallat JM
Neuromuscul Disord 2016 Apr-May;26(4-5):316-21. Epub 2016 Apr 5 doi: 10.1016/j.nmd.2016.01.004. PMID: 27067623
Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M, Goldman SA
Cell Stem Cell 2013 Feb 7;12(2):252-64. doi: 10.1016/j.stem.2012.12.002. PMID: 23395447Free PMC Article
Funalot B, Topilko P, Arroyo MA, Sefiani A, Hedley-Whyte ET, Yoldi ME, Richard L, Touraille E, Laurichesse M, Khalifa E, Chauzeix J, Ouedraogo A, Cros D, Magdelaine C, Sturtz FG, Urtizberea JA, Charnay P, Bragado FG, Vallat JM
Ann Neurol 2012 May;71(5):719-23. doi: 10.1002/ana.23527. PMID: 22522483

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