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Amyotrophic lateral sclerosis 27, juvenile(ALS27)

MedGen UID:
1840995
Concept ID:
C5830359
Disease or Syndrome
Synonym: ALS27
 
Gene (location): SPTLC1 (9q22.31)
 
Monarch Initiative: MONDO:0859529
OMIM®: 620285

Definition

Juvenile amyotrophic lateral sclerosis-27 (ALS27) is an autosomal dominant disorder characterized by early childhood-onset lower extremity spasticity manifesting as toe walking and gait abnormalities, followed by progressive lower motor neuron-mediated weakness without sensory signs or symptoms (Mohassel et al., 2021). For a discussion of genetic heterogeneity of amyotrophic lateral sclerosis, see ALS1 (105400). [from OMIM]

Clinical features

From HPO
Scapular winging
MedGen UID:
66822
Concept ID:
C0240953
Anatomical Abnormality
Abnormal protrusion of the scapula away from the surface of the back.
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).
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Tip-toe gait
MedGen UID:
98104
Concept ID:
C0427144
Finding
An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait.
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.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Lower limb spasticity
MedGen UID:
220865
Concept ID:
C1271100
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Jaw hyperreflexia
MedGen UID:
765822
Concept ID:
C3552908
Finding
Increased intensity of muscle tendon reflexes in jaw.
Impaired executive functioning
MedGen UID:
1617231
Concept ID:
C4544271
Mental or Behavioral Dysfunction
A disturbance of executive functioning, which is broadly defined as the set of abilities that allow for the planning, executing, monitoring, and self-correcting of goal-directed behavior while inhibiting task-irrelevant behavior. At least some degree of executive skill is needed to complete most cognitive tasks, and deficits in executive abilities are central to many clinical conditions, including fronto-temporal dementia.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Gowers sign
MedGen UID:
65865
Concept ID:
C0234182
Finding
A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs.
Progressive muscle weakness
MedGen UID:
68704
Concept ID:
C0240421
Finding
Generalized muscle weakness
MedGen UID:
155433
Concept ID:
C0746674
Sign or Symptom
Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Intrinsic hand muscle atrophy
MedGen UID:
351202
Concept ID:
C1864716
Finding
Atrophy of the intrinsic muscle groups of the hand, comprising the thenar and hypothenar muscles; the interossei muscles; and the lumbrical muscles.
Fiber type grouping
MedGen UID:
478824
Concept ID:
C3277194
Finding
An abnormal distribution of muscle fiber types in muscle tissue. Human skeletal muscle contains at least two fiber types recognizable by histochemical techniques. In transverse sections of normal skeletal muscle, type 1 and type 2 fibers are distributed in a random fashion. Grouping of fibers of the same type can be seen in certain peripheral neuropathies, thought to be due to reinnervation of denervated muscle fibers by sprouting axons. With grouping, motor units enlarge. The fibers of a motor unit, which are normally scattered, come to lie adjacent to one another. Histochemical examination shows groups of muscle fibers of the same histochemical type.
Quadriceps muscle atrophy
MedGen UID:
870170
Concept ID:
C4024603
Pathologic Function
Muscular atrophy involving the quadriceps muscle.
Angulated muscle fibers
MedGen UID:
1699728
Concept ID:
C5233187
Finding
Normal muscle fibers are polygonal-shaped in cross section, are multinucleated, and have minimal amounts of endomysial connective tissue. In contrast, angulated (also known as angular) muscle fibers have long and narrow vertices (corners) with sharp edges and a pointed tip.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Tongue fasciculations
MedGen UID:
65987
Concept ID:
C0239548
Finding
Fasciculations or fibrillation affecting the tongue muscle.
Tongue atrophy
MedGen UID:
66828
Concept ID:
C0241423
Finding
Wasting of the tongue.

Professional guidelines

PubMed

Rossi Sebastiano M, Ermondi G, Sato K, Otomo A, Hadano S, Caron G
Molecules 2022 Oct 19;27(20) doi: 10.3390/molecules27207063. PMID: 36296656Free PMC Article
Kacem I, Sghaier I, Peverelli S, Souissi E, Ticozzi N, Gharbi A, Ratti A, Berrechid AG, Silani V, Gouider R
Neurobiol Aging 2022 Dec;120:27-33. Epub 2022 Aug 14 doi: 10.1016/j.neurobiolaging.2022.08.002. PMID: 36108486

Recent clinical studies

Etiology

Hübers A, Just W, Rosenbohm A, Müller K, Marroquin N, Goebel I, Högel J, Thiele H, Altmüller J, Nürnberg P, Weishaupt JH, Kubisch C, Ludolph AC, Volk AE
Neurobiol Aging 2015 Nov;36(11):3117.e1-3117.e6. Epub 2015 Aug 15 doi: 10.1016/j.neurobiolaging.2015.08.005. PMID: 26362943
Castro-Costa CM, Oriá RB, Vale OC, Arruda JA, Horta WG, D'Almeida JA, Santos TJ, Ramos RS, Gifoni MA
Arq Neuropsiquiatr 2000 Dec;58(4):986-9. doi: 10.1590/s0004-282x2000000600002. PMID: 11105062
Greiner A, Schmausser B, Petzold K, Krüger H, Marx A
Acta Neuropathol 1996;91(1):67-71. doi: 10.1007/s004010050393. PMID: 8773148

Diagnosis

Rossi Sebastiano M, Ermondi G, Sato K, Otomo A, Hadano S, Caron G
Molecules 2022 Oct 19;27(20) doi: 10.3390/molecules27207063. PMID: 36296656Free PMC Article
Spataro R, Kousi M, Farhan SMK, Willer JR, Ross JP, Dion PA, Rouleau GA, Daly MJ, Neale BM, La Bella V, Katsanis N
Hum Genomics 2019 Apr 16;13(1):19. doi: 10.1186/s40246-019-0203-9. PMID: 30992063Free PMC Article
Castro-Costa CM, Oriá RB, Vale OC, Arruda JA, Horta WG, D'Almeida JA, Santos TJ, Ramos RS, Gifoni MA
Arq Neuropsiquiatr 2000 Dec;58(4):986-9. doi: 10.1590/s0004-282x2000000600002. PMID: 11105062
Otero Siliceo E, Arriada-Mendicoa N, Balderrama J
Dev Med Child Neurol 1998 Jun;40(6):425-8. PMID: 9652786

Prognosis

Lanteri P, Meola I, Canosa A, De Marco G, Lomartire A, Rinaudo MT, Albamonte E, Sansone VA, Lunetta C, Manera U, Vasta R, Moglia C, Calvo A, Origone P, Chiò A, Mandich P
Neurobiol Aging 2021 Jul;103:130.e1-130.e7. Epub 2021 Feb 3 doi: 10.1016/j.neurobiolaging.2021.01.029. PMID: 33637330
Hübers A, Just W, Rosenbohm A, Müller K, Marroquin N, Goebel I, Högel J, Thiele H, Altmüller J, Nürnberg P, Weishaupt JH, Kubisch C, Ludolph AC, Volk AE
Neurobiol Aging 2015 Nov;36(11):3117.e1-3117.e6. Epub 2015 Aug 15 doi: 10.1016/j.neurobiolaging.2015.08.005. PMID: 26362943
Dipti S, Childs AM, Livingston JH, Aggarwal AK, Miller M, Williams C, Crow YJ
Brain Dev 2005 Sep;27(6):443-6. Epub 2004 Dec 15 doi: 10.1016/j.braindev.2004.10.003. PMID: 16122634

Clinical prediction guides

Lanteri P, Meola I, Canosa A, De Marco G, Lomartire A, Rinaudo MT, Albamonte E, Sansone VA, Lunetta C, Manera U, Vasta R, Moglia C, Calvo A, Origone P, Chiò A, Mandich P
Neurobiol Aging 2021 Jul;103:130.e1-130.e7. Epub 2021 Feb 3 doi: 10.1016/j.neurobiolaging.2021.01.029. PMID: 33637330
Dipti S, Childs AM, Livingston JH, Aggarwal AK, Miller M, Williams C, Crow YJ
Brain Dev 2005 Sep;27(6):443-6. Epub 2004 Dec 15 doi: 10.1016/j.braindev.2004.10.003. PMID: 16122634

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