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Hereditary spastic paraplegia 9A(SPG9A)

MedGen UID:
1800401
Concept ID:
C5568978
Disease or Syndrome
Synonyms: Autosomal dominant spastic paraparesis; Bilateral cataracts, gastroesophageal reflux, and spastic paraparesis with amyotrophy; CATARACTS WITH MOTOR NEURONOPATHY, SHORT STATURE, AND SKELETAL ABNORMALITIES; Cataracts, motor neuronopathy, short stature and skeletal abnormalities; SPASTIC PARAPARESIS WITH AMYOTROPHY, CATARACTS, AND GASTROESOPHAGEAL REFLUX; Spastic paraplegia 9; SPASTIC PARAPLEGIA 9A, AUTOSOMAL DOMINANT
SNOMED CT: Cataracts, motor neuropathy, short stature, skeletal anomalies syndrome (1187465008); Autosomal dominant spastic paraplegia type 9A (1187465008); Spastic paraparesis, amyotrophy, cataracts, gastroesophageal reflux syndrome (1187465008)
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.
 
Gene (location): ALDH18A1 (10q24.1)
 
Monarch Initiative: MONDO:0011006
OMIM®: 601162
Orphanet: ORPHA447753

Definition

Autosomal dominant spastic paraplegia-9A is a neurologic disorder characterized by onset of slowly progressive spasticity mainly affecting the lower limbs. The age at onset usually ranges from adolescence to adulthood, and patients have gait difficulties, motor neuropathy, and dysarthria. Additional variable features include cerebellar signs, cataract, pes cavus, and urinary urgency (summary by Coutelier et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600). [from OMIM]

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Urinary urgency
MedGen UID:
39315
Concept ID:
C0085606
Finding
Urge incontinence is the strong, sudden need to urinate.
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).
Carpal bone hypoplasia
MedGen UID:
355049
Concept ID:
C1863749
Finding
Underdevelopment of one or more carpal bones.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
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.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Spastic gait
MedGen UID:
115907
Concept ID:
C0231687
Finding
Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg.
Resting tremor
MedGen UID:
66697
Concept ID:
C0234379
Sign or Symptom
A resting tremor occurs when muscles are at rest and becomes less noticeable or disappears when the affected muscles are moved. Resting tremors are often slow and coarse.
Motor polyneuropathy
MedGen UID:
82885
Concept ID:
C0271683
Disease or Syndrome
Inflammation or degeneration of the peripheral motor nerves.
Hoffmann sign
MedGen UID:
78828
Concept ID:
C0277839
Sign or Symptom
A Hoffmann test is performed by flicking the fingernail of the long finger, from dorsal to volar, on each hand while the hand was supported by the examiner's hand. The test was done with the neck in the neutral position and then with the neck maximally forward flexed. Any flexion of the ipsilateral thumb and/or index finger was interpreted as a positive test.
Corpus callosum atrophy
MedGen UID:
96560
Concept ID:
C0431370
Finding
The presence of atrophy (wasting) of the corpus callosum.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
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.
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.
Dysfunction of lateral corticospinal tracts
MedGen UID:
322009
Concept ID:
C1832671
Finding
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
Abnormal upper motor neuron morphology
MedGen UID:
871241
Concept ID:
C4025723
Anatomical Abnormality
Any structural anomaly that affects the upper motor neuron.
Specific learning disability
MedGen UID:
871302
Concept ID:
C4025790
Mental or Behavioral Dysfunction
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Hiatus hernia
MedGen UID:
483347
Concept ID:
C3489393
Acquired Abnormality
The presence of a hernia in which the upper part of the stomach, i.e., mainly the gastric cardia protrudes through the diaphragmatic esophageal hiatus.
Abnormal pelvic girdle bone morphology
MedGen UID:
866545
Concept ID:
C4020847
Anatomical Abnormality
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 9A

Recent clinical studies

Etiology

De Pace R, Skirzewski M, Damme M, Mattera R, Mercurio J, Foster AM, Cuitino L, Jarnik M, Hoffmann V, Morris HD, Han TU, Mancini GMS, Buonanno A, Bonifacino JS
PLoS Genet 2018 Apr;14(4):e1007363. Epub 2018 Apr 26 doi: 10.1371/journal.pgen.1007363. PMID: 29698489Free PMC Article
Wijemanne S, Jankovic J
Nat Rev Neurol 2015 Jul;11(7):414-24. Epub 2015 Jun 23 doi: 10.1038/nrneurol.2015.86. PMID: 26100751

Diagnosis

Wijemanne S, Jankovic J
Nat Rev Neurol 2015 Jul;11(7):414-24. Epub 2015 Jun 23 doi: 10.1038/nrneurol.2015.86. PMID: 26100751

Therapy

Wijemanne S, Jankovic J
Nat Rev Neurol 2015 Jul;11(7):414-24. Epub 2015 Jun 23 doi: 10.1038/nrneurol.2015.86. PMID: 26100751

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