, Alberto J. Espay2, Alfonso Fasano3 and Francesca Morgante4
(1)
Neurology Department, King’s College Hospital NHS Foundation Trust, London, UK
(2)
James J. and Joan A. Gardner Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA
(3)
Division of Neurology, University of Toronto Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease Toronto Western Hospital, UHN, Toronto, Ontario, Canada
(4)
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
2.1 An Introductory Note
Muscle tone refers to the resistance to passive stretching of a joint. The tone is abnormal either because of increased (hypertonia) or decreased (hypotonia, atonia) resistance to such manipulation. These tone abnormalities are common to several neurological diseases and may occur in combination with other motor disturbances such as weakness, dystonia, parkinsonism and neuromuscular diseases. Abnormalities of muscle tone might also be inferred from pathological conditions altering the mechanical properties of muscles or joints.
Hypertonic manifestations are spasticity, rigidity, paratonia, myotonia, stiffness and some forms of dystonia (see Chap. 6). When approaching patients with such disturbances, the following features should be searched for during clinical examination:
1.
Effect of velocity when stretching the joint (in order to distinguish rigidity from spasticity)
2.
Distribution of hypertonic muscles (antigravitary muscles vs. co-contraction of antagonistic sets of muscles)
3.
Temporal occurrence (continuous vs. paroxysmal)
4.
Presence of pyramidal signs, i.e. pyramidal weakness, abnormal cutaneous reflexes, increased muscle stretch reflexes, clonus and Babinski and Hoffmann signs
5.
Presence of hypokinesia with decrement during alternating repetitive motor tasks (‘sequence’ effect, true bradykinesia) and other motor features (dystonic movements, myoclonus, tremor)
Table 2.1 illustrates the main elements of the clinical examination that discriminate among disorders associated to increased muscular tone.
Table 2.1
Differential diagnosis of motor disturbances with increased muscle tone
Spasticity | Rigidity | Stiffness | Myotonia | Dystonia | Paratonia | |
|---|---|---|---|---|---|---|
Pattern of distribution | Arm flexors and leg extensors | Generalized or flexor or extension of limbs and trunk | Paraspinal muscles | Cranial/limb | Dystonic muscles | Limb/truncal |
Resistance to passive manipulation | Velocity dependent (clasp-knife phenomenon) | Velocity independent: equal (lead-pipe) or intermittent (cogwheel) throughout range of passive movement | Equal throughout range of passive movement | Equal throughout range of passive movementa | Little to no resistance in some focal dystonias | Variable resistance |
Strength | Weak | Normal (despite subjective weakness)b | Normal | Normal or weak | Normalb | Normal |
Hypokinesia with decrement | None | Present in rigidity due to parkinsonism | None | None | None | None |
Possible associated movements | None | Tremor, athetosis or dystonia | None | None | Dystonia, tremor, myoclonus | None |
Muscle stretch reflexes | Increased | Normal or slightly increased | Normal | Normal or increased | Normal | Normal or increased |
Plantar response | Extensor | Flexor (striatal toe may develop)c | Flexor | Flexor | Flexorc | Flexor |
Clonus | May be present | Absent | Absent | Absent | Absent | Absent |
Neurological diseases characterized by hypotonia involve the peripheral nervous system or—rarely—the cerebellum; hypotonia is usually a non-specific hallmark of many PNS and CNS diseases affecting the paediatric population (‘floppy baby’). Moreover, the sudden and short-lasting lack of muscle tone (‘atonia’) might be encountered in diseases determining an alteration of consciousness due to abrupt interruption of cerebral perfusion (cardiogenic and neurogenic syncope) or an epileptic seizure (atonic crises). Sudden atonia in absence of loss of consciousness might be caused by CNS diseases causing sudden loss of postural tone (cataplexy, drop attacks) or systemic or genetic diseases affecting the potassium channel at muscular level (primary and secondary periodic paralyses).
2.2 Hypertonia
2.2.1 How to Recognize
2.2.1.1 Spasticity
According to the definition of Lance in 1980, spasticity is ‘a motor disorder characterized by a velocity-dependent increase in tonic muscle stretch reflexes with increased muscular reflexes’. This definition was broadened by Young in 1989 [1] to include the Babinski response, hyperactive cutaneous reflexes, increased autonomic reflexes and abnormal postures. Moreover, the definition helps to distinguish spasticity from rigidity, which consists of a velocity-independent increase in tone. Spastic muscles react to slight stretching with strong shortening, impairing voluntary movements.
Spasticity is invariably associated with hyperreflexia and often pyramidal weakness and other signs indicating upper motor neuron involvement [2]. Animal studies have shown that spasticity is not caused by lesions only involving the primary motor area or the pyramids (where isolated weakness is observed) but rather by the damage of the premotor areas and the corticoreticulospinal pathways, leading to disinhibition of the stretch reflex within the spinal cord circuits. Spasticity can be suspected when antigravitary muscles are selectively involved, thus leading to a flexion of the affected upper limb (arm and wrist) and an extension of the affected lower limb (leg particularly).
Limb inspection, therefore, provides a first clue towards the recognition of spasticity. The affected upper limb shows adduction and internal rotation of the shoulder, flexion of the elbow and wrist, pronation of the forearm and flexion of the fingers with adduction of the thumb. The affected lower limb may exhibit knee extension with or without hip adduction and flexion, leading to scissoring or circumduction gait, respectively, and ankle plantar flexion. Depending on the distribution of spastic muscles, there may be a diplegic or paraparetic, quadriplegic or quadriparetic or a hemiplegic or hemiparetic pattern. Over time, spasticity tends to cause fixed flexion contractures at the elbows, wrists and fingers. A hemiparetic pattern of ambulation must be distinguished from the hemiparkinsonism of PD, where the gait base is not intermittently widened and the ipsilateral arm is held in extension (or just mildly flexed) rather than in flexion (Fig. 2.1).
Fig. 2.1
Hemiparesis vs. hemiparkinsonism. Spasticity leads to a hemiparetic pattern of gait (left), with arm and wrist flexion but ipsilateral leg extension (albeit with foot flexion and inversion), which circumducts during the swing phase of gait. Conversely, hemiparkinsonism (right) leads to arm extension (sometimes with dystonic posturing of the hand)
In spasticity, passive movements of the affected limb increase resistance in proportion with the acceleration of displacement. During slow passive range of movements, tone may not appear increased. When the velocity of passive mobilization is quickly increased, a corresponding increase in resistance is observed, followed by a release. This catch-and-yield phenomenon has been referred to as a clasp-knife phenomenon or ‘spastic catch’ and is a major hallmark of spasticity, which readily distinguishes it from the other common disorder of muscle tone, e.g. rigidity (see Chap. 1 and Table 2.1 of this chapter). According to the pattern of involved muscles, the clasp-knife phenomenon is greater in arm flexors and leg extensor muscles. This is also paralleled by a pyramidal distribution of weakness, with selective weakness of arm extensor and leg flexor muscles. Besides hyperreflexia (also including synkinetic reflexes and clonus), other pathologic reflexes are associated with spasticity [3] (Table 2.2).
Table 2.2
Additional clinical signs in spasticity
Signs | Description | |
|---|---|---|
Dorsiflexion of the great toe | Babinski | Obtained by stimulating the external portion (the outside) of the sole. The examiner begins the stimulation back at the heel and goes forward to the base of the toes |
Chaddock | Obtained by stimulating the skin over the lateral malleolus | |
Oppenheim | Obtained by stimulating the skin downwards of the medial side of the tibia | |
Plantar flexion of the toes | Rossolimo | Obtained by percussion of the tips of the toes |
Mendel–Bechterew | Obtained by percussion of the dorsum of the foot | |
Synkinetic movements | Marie–Foix sign | Passive plantar flexion of the toes or forcing the foot downwards causes dorsiflexion of the ankle and flexion of the knee and hip |
Strümpell’s phenomena | The patient’s attempt to flex the knee against resistance elicits an extensor plantar reflex | |
Tonic slow abduction of the little toe | Puusepp’s sign | Similar manoeuvre as Babinski sign |
2.2.1.2 Rigidity
Rigidity is the most common counterpart to complaints of ‘stiffness’ and may be a core component of parkinsonism (akinetic-rigid syndrome [4]) and of the rigidity and spasms from autoimmune encephalomyelopathies (stiff person syndrome [5]; see Chap. 1). Rigidity is recognized by limb resistance to passive manipulation, which limits the range of movement around the major joints and, unlike spasticity, is independent of the velocity with which the clinician tests the range of movement. This increase in resistance to passive movements may be constant (‘lead-pipe’) or intermittent (‘cogwheel’) but never magnified by movement acceleration (‘clasp-knife’ of spasticity).
2.2.1.3 Paratonia
Paratonia has been classically considered an erratic alteration of tone due to changes in passive movement due to insufficient relaxation, particularly in individuals with frontal-predominant cognitive impairment. It has also been defined as a form of hypertonia with an involuntary and variable resistance during passive movement. Because it appears as if the patient is ‘fighting’ the manipulation, it has also been referred to as oppositional paratonia (‘gegenhalten’ or ‘paratonic rigidity’). A different variant, also associated with frontal lobe impairment, is the facilitory paratonia (‘mitgehen’ or active assistance) when patients seem as if they are ‘trying to help’ [6]. The degree of resistance depends on the speed of movement and is proportional to the force applied (e.g. slow is associated with low resistance, fast with high resistance [7]). Paratonia is not specific for any specific dementia type and invariably increases with progression of the underlying disease.
2.2.1.4 Myotonic Disorders
Clinical myotonia is characterized by incomplete relaxation of muscles following either voluntary muscle contraction or direct muscle percussion [8]. Accordingly, it may produce stiffness, cramping or an aching sensation in affected muscles. Myotonia is a sign occurring in neuromuscular disorders caused by muscle ion channel dysfunction. Depending on the affected body part, myotonia can impair ambulation, reduce dexterity, impair neck movement and interfere with chewing or eyelid opening. The difficulty to relax muscles involved by myotonia may be relatively transient (lasting seconds/minutes) or prolonged (hours and sometimes days), producing abnormal postures or stiffness, which may be mistaken for dystonia, stiff person syndrome or rigidity. Myotonia may also affect smooth muscles, thus causing gastrointestinal symptoms such as abdominal pain, diarrhoea, bloating and dysphagia. A distinct clinical feature of myotonia is the tendency to diminish with repeated muscle contractions (‘warm-up’ phenomenon) opposite to paramyotonia in which muscle relaxation becomes worse with repetitive contractions (‘paradoxical myotonia’).
2.2.2 How to Distinguish from Related Disorders and Reach a Diagnosis
Upper motor neuron lesions located anywhere between the primary motor cortex and the corticospinal tract in the dorsolateral spinal cord can lead to spasticity. Spasticity develops contralaterally to a supramedullary lesion but ipsilateral to a lesion below the pyramidal decussation. Neurological disorders associated with spasticity might be nonprogressive or progressive. Nonprogressive causes of spasticity are cerebrovascular disease, spinal cord lesions (i.e. myelitis, trauma, severe syringomyelia), cerebral palsy and head trauma (Table 2.3); progressive neurological conditions associated with spasticity are demyelinating diseases, leukoencephalopathies and neurodegenerative diseases affecting the upper motor neuron (hereditary spastic paraplegia, primary lateral sclerosis), the basal ganglia (‘pallido-pyramidal conditions’, such as neurodegenerations with brain iron accumulation; see also Chap. 6) or the cerebellum (genetic ataxias, see also Chap. 4).
Table 2.3
Acquired causes of spastic paraparesis
Category | Main disorders |
|---|---|
Structural lesions of the brain or spinal cord | Cord compression (spondylodegenerative, neoplastic) Tethered cord syndrome Spinal cord arteriovenous malformation |
Demyelinating/dysmyelinating disorders | Multiple sclerosis Neuromyelitis optica Adrenomyeloneuropathy Krabbe disease Metachromatic leukodystrophy Vitamin B12 deficiency Copper deficiency Mitochondrial diseases |
Infectious | HTLV1 myelopathy (tropical spastic paraplegia) HIV myelopathy Tertiary syphilis (pachymeningitis) |
Neurodegenerative | Amyotrophic lateral sclerosis Primary lateral sclerosis Distal hereditary motor neuropathy Friedreich ataxia Spinocerebellar ataxia type 3 |
Immune mediated | Stiff person syndrome |
Toxic | Zinc (associated with low serum copper levels) Cycad poisoning Lathyrism Konzo |
Hereditary spastic paraplegias (HSP) constitute a heterogeneous group of neurodegenerative diseases caused by genetic mutations that affect the longest corticospinal tract axons, with frequent involvement also of ascending fibre tracts (dorsal columns, spinocerebellar tracts). Their core clinical features comprise progressive weakness and spasticity, extensor plantar responses and hyperreflexia of deep tendon reflexes in lower limbs.
So far, more than 60 loci have been assigned to HSP including a wide range of phenotypically heterogeneous diseases in terms of age at onset, progression and phenotype, in which spasticity and weakness can be isolated (uncomplicated HSP) or combined with other neurological symptoms (complicated HSP). Nevertheless, the same gene might be associated to complicated or uncomplicated HSP, thus making the genotype–phenotype correlations extremely difficult (for a recent review, see [9]).
Tables 2.4, 2.5 and 2.6 present a syndromic approach to the differential diagnosis of hereditary HSPs (autosomal dominant, autosomal recessive, X-linked).
Table 2.4
Autosomal dominant hereditary spastic paraparesis
Disease | Gene/protein | Onset | Epilepsy | Ataxia | Neuropathy | Upper limb spasticity | Cognitive impairment | Other movement disorders | Ocular manifestations | Other |
|---|---|---|---|---|---|---|---|---|---|---|
SPG3A | ATL1/atlastin | First decade | Yes | Yes | Sensorimotor axonal PNP with pes cavus; cranial neuropathies | Yes | Yes + learning disabilities | – | Optic atrophy | Thinning of the corpus callosum |
SPG4 | SPAST/spastin | Variable (most in fourth decade) | Yes | Yes (dorsal column involvement) | PNP with pes cavus | Yes | Yes, with executive dysfunction | – | – | Bladder dysfunction, psychosis, posterior fossa abnormalities (e.g. congenital arachnoid cysts), white matter lesions, amyotrophy of distal muscles |
SPG6 | NIPA1/NIPA1 | Adolescence | Yes | – | PNP | Yes | Yes | Facial dystonia | Dysarthria, amyotrophy of distal muscles | |
SPG8 | KIAA0196/strumpellin | Adults | – | – | – | – | – | – | – | – |
SPG10 | KIF5A/kinesinHC5A | First decade | – | – | PNP | – | Yes | Parkinsonism | Retinitis pigmentosa | Dysautonomia, amyotrophy of distal muscles, deafness |
SPG12 | RTN2/reticulon2 | First decade | – | – | – | – | – | – | – | – |
SPG13 | HSP01/HSP60 | Variable | – | – | – | – | – | Generalized dystonia (responding to deep brain stimulation) | – | Loss of vibratory sensation, without ataxia |
SPG17 | BSCL2/Seipin | Adolescence | – | – | – | – | – | – | – | Amyotrophy of distal muscles with severe reduction of CMAP on nerve conduction studies (Silver syndrome) |
SPG29 | Unknown | Adolescence | – | – | – | – | – | – | – | Pes cavus Deafness Hiatus hernia Hyperbilirubinaemia |
SPG31 | REEP1/REEP1 | First decade | – | Yes (cerebellar) | PNP with pes cavus | – | Yes | Tremor | – | Amyotrophy of distal muscles |
SPG33 | ZFYVE27/protrudin | Adult | – | – | – | – | – | – | – | Pes equinus |
SPG36 | Unknown | Variable | – | – | Sensory PNP | – | – | – | – | – |
SPG37 | Unknown | Variable | – | – | – | – | – | – | – | – |
SPG38 | Unknown | Variable | – | – | PNP | – | – | – | – | Amyotrophy of distal muscles |
SPG40 | Unknown | Adult | – | – | – | Yes, with hyperreflexia | Yes | – | – | – |
SPG41 | Unknown | Adolescence | – | – | – | – | – | – | – | – |
SPG42 | SLC33A1/ACoa carrier | Variable | – | – | – | – | – | – | – | – |
SPG72 | REEP2/REEP2 | First decade | – | – | – | – | – | – | – | – |
Table 2.5
Autosomal recessive hereditary spastic paraparesis
Disease | Gene/protein | Onset | Epilepsy | Ataxia | Neuropathy | Upper limb spasticity | Cognitive impairment | Other movement disorders | Ocular manifestations | Other |
|---|---|---|---|---|---|---|---|---|---|---|
SPG5A | CYP7B1/OAH1 | Variable | – | Yes (cerebellar) | – | – | – | – | Optic atrophy | White matter lesions—abnormal MEP, SSEP, VEP, BAEP |
SPG7 | PGN/paraplegin | Variable | – | Yes (cerebellar) | PNP with pes cavus | – | Yes, with attention and executive dysfunction | Cerebellar syndrome | Supranuclear palsy Optic atrophy or abnormalities on optical coherence tomography | Thinning of corpus callosum Scoliosis |
SPG11 | KIAA1840/spatacsin | Variable | Yes | Yes (cerebellar) | PNP (axonal) | Yes, with weakness and amyotrophy (also cause of juvenile ALS [ALS5]) | Yes, with LDs | Parkinsonism with action tremor Cerebellar syndrome | Maculopathy | Thinning of corpus callosum |
SPG14 | Unknown | Adult | – | – | Motor PNP | – | Yes | – | – | – |
SPG15 | ZFYVE26/spastizin | First decade | Yes | Yes (cerebellar) | PNP | – | Yes, with LDs | Cerebellar syndrome | Pigmentary retinopathy | Thinning of corpus callosum |
SPG18 | ERLIN2/SPFH2 | First decade | Yes | – | – | – | Yes, with LDs | – | – | Congenital hip dislocation Multiple joint contractures |
SPG20 | SPG20/spartin | First decade | – | Yes (cerebellar) | – | Yes | Yes, with LDs | Cerebellar syndrome | – | Dysarthria Pathological euphoria and crying White matter lesions |
SPG21 | ACP33/maspardin | First decade | – | Yes (cerebellar) | – | – | Yes | Parkinsonism | – | Thinning of the corpus callosum with callosal disconnection syndrome White matter lesions |
SPG23 | Unknown | First decade | – | – | – | – | Yes | Tremor | Pigmentary abnormalities Facial and skeletal dysmorphism | |
SPG24 | Unknown | First decade | – | – | – | – | – | – | – | Pseudobulbar signs |
SPG25 | Unknown | Adult | – | – | PNP | – | – | – | Cataracts | Disc herniation |
SPG26 | B4GALNT1/B4GALNT1 | First decade | – | Yes (cerebellar) | PNP | – | Yes, with LDs | – | – | Amyotrophy of distal muscles Cortical atrophy White matter lesions |
SPG27 | Unknown | Variable | – | – | PNP | – | Yes, with LDs | – | – | Dysarthria |
SPG28 | DDHD1/PAPLA1 | First decade | – | – | PNP (axonal) | – | – | – | Saccadic pursuit | – |
SPG30 | KIF1A/kinesin 3 | Adolescence | – | Yes (cerebellar) | Sensory PNP | – | – | – | – | Amyotrophy of distal muscles Hypoacusis |
SPG32 | Unknown | First decade | – | – | – | – | Yes, with LDs | – | – | Pontine dysraphism Thinning of the corpus callosum |
SPG35 | FA2H/FA2H | First decade | Yes | – | – | – | Yes, with LDs | – | – | – |
SPG39 | NTE/PNPLA6 | First decade | – | – | PNP (axonal) | – | – | – | – | Amyotrophy of distal muscles |
SPG43 | C19orf12/C19ORF12 | Variable | – | – | Sensory and motor PNP (axonal) | – | – | – | Bilateral optic atrophy | Amyotrophy of distal muscles Iron deposits in the globus pallidus |
SPG44 | GJC2/connexin 47 | Adult | – | Yes (cerebellar) | – | Yes | Yes | Cerebellar syndrome | – | Dysarthria White matter lesions (hypomyelinating leukodystrophy) Thinning of the corpus callosum Pes cavus Scoliosis |
SPG45 | Unknown | First decade | – | – | – | – | Yes, with LDs | – | Pendular nystagmus Optic atrophy | – |
SPG46 | GBA2/GBA2 | First decade | – | Yes (cerebellar) | – | – | Yes, with LDs | Cerebellar syndrome | Cataracts | Cerebellar atrophy and thinning of the corpus callosum Hypogonadism in males |
SPG47, 50–52 | AP4(B,M,E,S)1/AP4(B,M,E,S)1 | First decade | Yes | Yes (cerebellar) | – | Yes | Yes, with LDs | Cerebellar syndrome | Neonatal hypotonia progressing to spasticity Periventricular leukodystrophy with thinning of the corpus callosum and cerebellar hypoplasia Microcephaly Growth retardation | |
SPG48 | KIAA0415/AP5Z1 | Adult | – | – | – | – | – | – | – | Urinary incontinence Spinal cord hyperintensities |
SPG49 | TECPR2/KIAA0329 | First decade | – | Yes (cerebellar) | – | – | Yes, with LDs | Cerebellar syndrome | – | Thinning of the corpus callosum Dysmorphic features (short stature, mild brachycephalic microcephaly, round face, low anterior hairline, dental crowding, short broad neck, chubby appearance) Central apnoea |
SPG53 | VPS37A/VPS37A | First decade | – | – | – | Yes | Yes, with LDs | – | – | Kyphosis and pectus carinatum Hypertrichosis |
SPG54 | DDHD2/DDHD2 | First decade | – | – | – | – | Yes, with LDs | – | Strabismus Optic nerve hypoplasia | Dysarthria and dysphagia Short stature and laterally deviated feet Thinning of the corpus callosum and white matter lesions Abnormal lipid peak on brain spectroscopy (highest in basal ganglia and thalamus) |
SPG55 | C12orf65/C12ORF65 | First decade | – | – | PNP | – | – | – | Optic atrophy | Pes equinovarus |
SPG56 | CYP2U1 /CYP2U1 | First decade | – | – | PNP (axonal—subclinical) | Yes | Yes | Upper limb dystonia | Thinning of the corpus callosum with white matter lesions Globus pallidus calcifications | |
SPG57 | TFG/TFG | First decade | – | – | PNP | – | – | – | Optic atrophy | – |
SPG58 | KIF1C/kinesin family member 1C | First decade | – | Yes | – | – | Yes, with LDs | Chorea, myoclonus | Ptosis | Hypodontia Deafness Short stature White matter lesions |
SPG59 | USP8/ubiquitin-specific protease 8 | First decade | – | – | – | – | Borderline intelligence | – | Nystagmus | – |
SPG60 | WDR48/WD repeat domain 48 | First decade | – | – | PNP (in lower limbs) | – | – | – | Nystagmus | – |
SPG61 | ARL6IP1/ADP-ribosylation factor-like 6 | First decade | – | – | PNP | – | – | – | – | Acromutilation with loss of terminal digits |
SPG62 | ERLIN1/ER lipid raft associated 1 | First decade | – | – | – | – | – | – | – | – |
SPG63 | AMPD2/AMP deaminase 2 | First decade | – | – | – | – | – | – | – | Thinning of the corpus callosum with white matter lesions Short stature and low weight |
SPG64 | ENTPD1/ectonucleoside triphosphate di-phosphohydrolase 1 | First decade | – | – | – | – | Borderline intelligence | – | – | Pes equinovarus Aggressiveness Delayed puberty Microcephaly |
SPG65 | NT5C2/5’-nucleotidase, cytosolic II | First decade | – | – | – | – | Yes, with LDs | – | – | Thinning of the corpus callosum with hypomyelination and small bilateral cystic occipital leukomalacia Pes equinovarus |
SPG66 | ARS1/Arylsulfatase family, member 1 | First decade | – | Yes (cerebellar) | PNP | – | Borderline intelligence | Cerebellar syndrome | Thinning of the corpus callosum and cerebellar hypoplasia Colpocephaly Pes equinovarus | |
SPG67 | PGAP1/post-GPI attachment to proteins 1 | First decade | – | Yes (cerebellar) | – | Borderline intelligence | Cerebellar syndrome | – | Distended abdomen Agenesia of the corpus callosum Vermis hypoplasia Hypomyelination | |
SPG68 | FLRT1/fibronectin leucine-rich transmembrane protein 1 | First decade | – | – | PNP with amyotrophy and foot drop | – | – | – | Nystagmus Optic atrophy | – |
SPG69 | RAB3GAP2/RAB3 GTPase-activating protein subunit 2 | First decade | – | – | – | – | Yes, with LDs | – | Cataracts | Deafness |
SPG70 | MARS/methionyl-tRNA synthetase | First decade | – | – | – | – | Borderline intelligence | – | – | Scoliosis Bilateral Achilles’ contracture Nephrotic syndrome |
SPG71 | ZFR/zinc finger RNA-binding protein | First decade | – | – | – | – | –
Related posts: Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Get Clinical Tree app for offline access
|
