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Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures

MedGen UID:
322470
•Concept ID:
C1834690
•
Disease or Syndrome
Synonyms: KUGELBERG-WELANDER SYNDROME, AUTOSOMAL DOMINANT; SPINAL MUSCULAR ATROPHY, CHILDHOOD, PROXIMAL, AUTOSOMAL DOMINANT; SPINAL MUSCULAR ATROPHY, JUVENILE, PROXIMAL, AUTOSOMAL DOMINANT; Spinal muscular atrophy, lower extremity predominant 1, autosomal dominant; Spinal muscular atrophy, lower extremity-predominant 1, AD
SNOMED CT: Autosomal dominant childhood-onset proximal spinal muscular atrophy (772129007); Lower extremity-predominant autosomal dominant proximal spinal muscular atrophy (772129007); SMALED - spinal muscular atrophy, lower extremity, dominant (772129007); Spinal muscular atrophy with lower extremity predominance (772129007)
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): DYNC1H1 (14q32.31)
 
Monarch Initiative: MONDO:0008026
OMIM®: 158600
Orphanet: ORPHA209341

Definition

Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by degeneration of spinal cord motor neurons resulting in muscle weakness. SMALED shows autosomal dominant inheritance with muscle weakness predominantly affecting the proximal lower extremities (Harms et al., 2010). The most common form of SMA (see, e.g., SMA1, 253300) shows autosomal recessive inheritance and is due to mutation in the SMN1 gene (600354) on chromosome 5q. Genetic Heterogeneity of Lower Extremity-Predominant Spinal Muscular Atrophy See also SMALED2A (615290) and SMALED2B (618291), both of which are caused by mutation in the BICD2 gene (609797) on chromosome 9q22. SMALED2A and SMALED2B differ in age at onset and severity, with SMALED2B being more severe. [from OMIM]

Additional description

From MedlinePlus Genetics
Spinal muscular atrophy with lower extremity predominance (SMA-LED) is characterized by muscle weakness and wasting (atrophy) in the lower limbs, most severely affecting the thigh muscles (quadriceps). (In SMA-LED, the "D" stands for dominant, which refers to the inheritance pattern of this condition.) The loss of nerve cells that control muscle movement (motor neurons) leads to atrophy of the muscles in the lower limbs. Affected individuals often have a waddling or unsteady walk and walk on the balls of their feet. They may have difficulty rising from a seated position and climbing stairs. Some people with SMA-LED also have weakness in upper limb muscles.

Joint deformities (contractures) in the hips, knees, feet, and ankles can occur in SMA-LED, and in severe cases are present from birth and can impair walking. Some individuals with this disorder have rigidity of joints (arthrogryposis) in their shoulders, elbows, and hands.

In most people with SMA-LED, the muscle problems are apparent in infancy or early childhood; however, about one-quarter of affected individuals do not develop muscle weakness until adulthood. The muscle weakness and related health problems typically do not worsen over time.  https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy-with-lower-extremity-predominance

Clinical features

From HPO
Decreased patellar reflex
MedGen UID:
478814
•Concept ID:
C3277184
•
Finding
Decreased intensity of the patellar reflex (also known as the knee jerk reflex).
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Abnormal foot morphology
MedGen UID:
1762829
•Concept ID:
C5399834
•
Anatomical Abnormality
An abnormality of the skeleton of foot.
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Waddling gait
MedGen UID:
66667
•Concept ID:
C0231712
•
Finding
Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.
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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.
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Global developmental delay
MedGen UID:
107838
•Concept ID:
C0557874
•
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
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Somatic sensory dysfunction
MedGen UID:
1790456
•Concept ID:
C5551413
•
Finding
An abnormality of the primary sensation that is mediated by peripheral nerves (pain, temperature, touch, vibration, joint position). The word hypoesthesia (or hypesthesia) refers to a reduction in cutaneous sensation to a specific type of testing.
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Spinal muscular atrophy
MedGen UID:
7755
•Concept ID:
C0026847
•
Disease or Syndrome
Spinal muscular atrophy (SMA) is characterized by muscle weakness and atrophy resulting from progressive degeneration and irreversible loss of the anterior horn cells in the spinal cord (i.e., lower motor neurons) and the brain stem nuclei. The onset of weakness ranges from before birth to adulthood. The weakness is symmetric, proximal > distal, and progressive. Before the genetic basis of SMA was understood, it was classified into clinical subtypes based on maximum motor function achieved; however, it is now apparent that the phenotype of SMN1-associated SMA spans a continuum without clear delineation of subtypes. With supportive care only, poor weight gain with growth failure, restrictive lung disease, scoliosis, and joint contractures are common complications; however, newly available targeted treatment options are changing the natural history of this disease.
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Difficulty running
MedGen UID:
108251
•Concept ID:
C0560346
•
Finding
Reduced ability to run.
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Proximal lower limb amyotrophy
MedGen UID:
373171
•Concept ID:
C1836767
•
Finding
Muscular atrophy affecting proximally located muscles of the legs, i.e., of the thigh.
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Proximal muscle weakness in lower limbs
MedGen UID:
356423
•Concept ID:
C1866010
•
Finding
A lack of strength of the proximal muscles of the legs.
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Type 2 muscle fiber predominance
MedGen UID:
478817
•Concept ID:
C3277187
•
Finding
An abnormal predominance of type II muscle fibers (in general, this feature can only be observed on muscle biopsy).
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EMG: neuropathic changes
MedGen UID:
867363
•Concept ID:
C4021727
•
Finding
The presence of characteristic findings of denervation on electromyography (fibrillations, positive sharp waves, and giant motor unit potentials).
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal dominant childhood-onset proximal spinal muscular atrophy without contractures
Follow this link to review classifications for Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures in Orphanet.

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