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Congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome(ASNSD)

MedGen UID:
816301
Concept ID:
C3809971
Disease or Syndrome
Synonyms: ASNS DEFICIENCY; Asparagine synthetase deficiency
SNOMED CT: Congenital microcephaly, severe encephalopathy, progressive cerebral atrophy syndrome (782757004); Asparagine synthetase deficiency (782757004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ASNS (7q21.3)
 
Monarch Initiative: MONDO:0014258
OMIM®: 615574
Orphanet: ORPHA391376

Disease characteristics

Excerpted from the GeneReview: Asparagine Synthetase Deficiency
Asparagine synthetase deficiency (ASD) mainly presents as a triad of congenital microcephaly, severe developmental delay, and axial hypotonia followed by spastic quadriplegia. Low cerebrospinal fluid (CSF) asparagine level can help the clinician in differentiating this disorder from others. In most cases age of onset of apnea, excessive irritability, and seizures is soon after birth. Affected individuals typically do not acquire any developmental milestones. Spastic quadriplegia can lead to severe contractures of the limbs and neurogenic scoliosis. Feeding difficulties (gastroesophageal reflux disease, frequent vomiting, swallowing dysfunction, and gastroesophageal incoordination) are a significant problem in most affected individuals. A majority have cortical blindness. MRI findings are nonspecific but may include generalized atrophy and simplified gyral pattern. [from GeneReviews]
Authors:
Majid Alfadhel  |  Ayman W El-Hattab   view full author information

Additional descriptions

From OMIM
ASNS deficiency (ASNSD) is an autosomal recessive severe neurologic disorder characterized by microcephaly, severely delayed psychomotor development, progressive encephalopathy, cortical atrophy, and seizure or hyperekplexic activity. The disorder may show onset in utero or at birth and may result in early death (summary by Ruzzo et al., 2013); it may also present with early normal development followed by infantile-onset seizures and neurodevelopmental delays (Sacharow et al., 2018).  http://www.omim.org/entry/615574
From MedlinePlus Genetics
Asparagine synthetase deficiency is a condition that causes neurological problems in affected individuals starting soon after birth. Most people with this condition have an unusually small head size (microcephaly) that worsens over time due to loss (atrophy) of brain tissue. They also have severe developmental delay that affects both mental and motor skills (psychomotor delay). Affected individuals cannot sit, crawl, or walk and are unable to communicate verbally or nonverbally. The few affected children who achieve developmental milestones often lose these skills over time (developmental regression).

Most individuals with asparagine synthetase deficiency have exaggerated reflexes (hyperreflexia) and weak muscle tone (hypotonia). The muscle problems worsen through childhood and lead to muscle stiffness, uncontrolled movements, and ultimately, paralysis of the arms and legs (spastic quadriplegia). Many affected individuals also have recurrent seizures (epilepsy). Not all affected people experience the same type of seizure. The most common types involve a loss of consciousness, muscle rigidity, and convulsions (tonic-clonic); involuntary muscle twitches (myoclonic); or abnormal muscle contraction (tonic). People with asparagine synthetase deficiency may have an exaggerated startle reaction (hyperekplexia) to unexpected stimuli. Some affected individuals have blindness due to impairment of the area of the brain responsible for processing vision, called the occipital cortex (cortical blindness).

People with asparagine synthetase deficiency typically do not survive past childhood.  https://medlineplus.gov/genetics/condition/asparagine-synthetase-deficiency

Clinical features

From HPO
Large hands
MedGen UID:
98097
Concept ID:
C0426870
Finding
Long foot
MedGen UID:
154365
Concept ID:
C0576225
Finding
Increased back to front length of the foot.
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
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.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Simple ear
MedGen UID:
140913
Concept ID:
C0431483
Congenital Abnormality
The pinna has fewer folds and grooves than usual.
Clonus
MedGen UID:
40341
Concept ID:
C0009024
Sign or Symptom
A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Sleep apnea
MedGen UID:
11458
Concept ID:
C0037315
Disease or Syndrome
An intermittent cessation of airflow at the mouth and nose during sleep is known as sleep apnea. Apneas that last at least 10 seconds are considered significant, but individuals with sleep apnea may experience apneas lasting from 20 seconds up to 2 or 3 minutes. Patients may have up to 15 events per hour of sleep.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Clonic seizure
MedGen UID:
66708
Concept ID:
C0234535
Disease or Syndrome
A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive.
Global brain atrophy
MedGen UID:
66840
Concept ID:
C0241816
Pathologic Function
Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Spastic tetraplegia
MedGen UID:
98433
Concept ID:
C0426970
Disease or Syndrome
Spastic paralysis affecting all four limbs.
Cortical dysplasia
MedGen UID:
98129
Concept ID:
C0431380
Congenital Abnormality
The presence of developmental dysplasia of the cerebral cortex.
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.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Delayed myelination
MedGen UID:
224820
Concept ID:
C1277241
Finding
Delayed myelination.
Exaggerated startle response
MedGen UID:
329357
Concept ID:
C1740801
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Cerebellar vermis hypoplasia
MedGen UID:
333548
Concept ID:
C1840379
Finding
Underdevelopment of the vermis of cerebellum.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Dilated fourth ventricle
MedGen UID:
376050
Concept ID:
C1847117
Finding
An abnormal dilatation of the fourth cerebral ventricle.
Hypoplasia of the pons
MedGen UID:
341246
Concept ID:
C1848529
Finding
Underdevelopment of the pons.
Caudate atrophy
MedGen UID:
346745
Concept ID:
C1858116
Disease or Syndrome
EEG with burst suppression
MedGen UID:
369943
Concept ID:
C1969156
Finding
The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Profound global developmental delay
MedGen UID:
766364
Concept ID:
C3553450
Disease or Syndrome
A profound delay in the achievement of motor or mental milestones in the domains of development of a child.
Dilated third ventricle
MedGen UID:
870494
Concept ID:
C4024941
Finding
An increase in size of the third ventricle.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Reduced cerebral white matter volume
MedGen UID:
1815057
Concept ID:
C5706151
Finding
An abnormally low volume of the white matter of the brain.
Diaphragmatic eventration
MedGen UID:
8359
Concept ID:
C0011981
Congenital Abnormality
A congenital failure of muscular development of part or all of one or both hemidiaphragms, resulting in superior displacement of abdominal viscera and altered lung development.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
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.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Anatomical Abnormality
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Primary microcephaly
MedGen UID:
383046
Concept ID:
C2677180
Finding
Head circumference below 2 standard deviations below the mean for age and gender at birth.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
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.
Hypoasparaginemia
MedGen UID:
1671021
Concept ID:
C4732910
Finding
A decreased amount of asparagine in the blood.
Prominent nasal tip
MedGen UID:
383839
Concept ID:
C1856118
Finding
Sloping forehead
MedGen UID:
346640
Concept ID:
C1857679
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
Moderate to late preterm birth
MedGen UID:
886897
Concept ID:
C4054482
Finding
Birth at 32 to 36 completed weeks of gestation.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Optic nerve hypoplasia
MedGen UID:
137901
Concept ID:
C0338502
Disease or Syndrome
Underdevelopment of the optic nerve.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation.
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.
Esodeviation
MedGen UID:
1641033
Concept ID:
C4551734
Disease or Syndrome
A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome
Follow this link to review classifications for Congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome in Orphanet.

Professional guidelines

PubMed

Tohyama J, Nakashima M, Nabatame S, Gaik-Siew C, Miyata R, Rener-Primec Z, Kato M, Matsumoto N, Saitsu H
J Hum Genet 2015 Apr;60(4):167-73. Epub 2015 Jan 29 doi: 10.1038/jhg.2015.5. PMID: 25631096
Lanzi G, D'Arrigo S, Drumbl G, Uggetti C, Fazzi E
Funct Neurol 2003 Apr-Jun;18(2):71-5. PMID: 12911136
Somer M
J Med Genet 1993 Nov;30(11):932-6. doi: 10.1136/jmg.30.11.932. PMID: 8301648Free PMC Article

Recent clinical studies

Etiology

Salpietro V, Maroofian R, Zaki MS, Wangen J, Ciolfi A, Barresi S, Efthymiou S, Lamaze A, Aughey GN, Al Mutairi F, Rad A, Rocca C, Calì E, Accogli A, Zara F, Striano P, Mojarrad M, Tariq H, Giacopuzzi E, Taylor JC, Oprea G, Skrahina V, Rehman KU, Abd Elmaksoud M, Bassiony M, El Said HG, Abdel-Hamid MS, Al Shalan M, Seo G, Kim S, Lee H, Khang R, Issa MY, Elbendary HM, Rafat K, Marinakis NM, Traeger-Synodinos J, Ververi A, Sourmpi M, Eslahi A, Khadivi Zand F, Beiraghi Toosi M, Babaei M, Jackson A; SYNAPS Study Group, Bertoli-Avella A, Pagnamenta AT, Niceta M, Battini R, Corsello A, Leoni C, Chiarelli F, Dallapiccola B, Faqeih EA, Tallur KK, Alfadhel M, Alobeid E, Maddirevula S, Mankad K, Banka S, Ghayoor-Karimiani E, Tartaglia M, Chung WK, Green R, Alkuraya FS, Jepson JEC, Houlden H
Am J Hum Genet 2024 Jan 4;111(1):200-210. Epub 2023 Dec 20 doi: 10.1016/j.ajhg.2023.11.012. PMID: 38118446Free PMC Article
Ivanov I, Pacheva I, Yordanova R, Sotkova I, Galabova F, Gaberova K, Panova M, Gheneva I, Tsvetanova T, Noneva K, Dimitrova D, Markov S, Sapundzhiev N, Bichev S, Savov A
CNS Neurol Disord Drug Targets 2023;22(2):207-214. doi: 10.2174/1871527321666220221100704. PMID: 35189806
Tohyama J, Akasaka N, Osaka H, Maegaki Y, Kato M, Saito N, Yamashita S, Ohno K
Brain Dev 2008 May;30(5):349-55. Epub 2007 Dec 11 doi: 10.1016/j.braindev.2007.10.006. PMID: 18065176
Barth PG
Brain Dev 1993 Nov-Dec;15(6):411-22. doi: 10.1016/0387-7604(93)90080-r. PMID: 8147499
Billard C, Dulac O, Bouloche J, Echenne B, Lebon P, Motte J, Robain O, Santini JJ
Neuropediatrics 1989 Feb;20(1):12-9. doi: 10.1055/s-2008-1071258. PMID: 2654691

Diagnosis

Yin X, Tang B, Mao X, Peng J, Zeng S, Wang Y, Jiang H, Li N
J Hum Genet 2018 Sep;63(9):971-980. Epub 2018 Jun 18 doi: 10.1038/s10038-018-0478-z. PMID: 29915213
O'Brien A, Marshall CR, Blaser S, Ray PN, Yoon G
Eur J Hum Genet 2017 Jun;25(6):775-778. Epub 2017 Apr 5 doi: 10.1038/ejhg.2017.39. PMID: 28378817Free PMC Article
Kurata H, Terashima H, Nakashima M, Okazaki T, Matsumura W, Ohno K, Saito Y, Maegaki Y, Kubota M, Nanba E, Saitsu H, Matsumoto N, Kato M
Clin Genet 2016 Nov;90(5):437-444. Epub 2016 Jul 4 doi: 10.1111/cge.12813. PMID: 27246907
Tohyama J, Nakashima M, Nabatame S, Gaik-Siew C, Miyata R, Rener-Primec Z, Kato M, Matsumoto N, Saitsu H
J Hum Genet 2015 Apr;60(4):167-73. Epub 2015 Jan 29 doi: 10.1038/jhg.2015.5. PMID: 25631096
Lanzi G, D'Arrigo S, Drumbl G, Uggetti C, Fazzi E
Funct Neurol 2003 Apr-Jun;18(2):71-5. PMID: 12911136

Therapy

Yin X, Tang B, Mao X, Peng J, Zeng S, Wang Y, Jiang H, Li N
J Hum Genet 2018 Sep;63(9):971-980. Epub 2018 Jun 18 doi: 10.1038/s10038-018-0478-z. PMID: 29915213
Manuskiatti W, Iamphonrat T, Wanitphakdeedecha R, Eimpunth S
Dermatol Surg 2013 Jan;39(1 Pt 1):111-20. Epub 2012 Dec 3 doi: 10.1111/dsu.12030. PMID: 23205717
Caraballo RH, Pozo AN, Gomez M, Semprino M
Pediatr Neurol 2011 Apr;44(4):259-64. doi: 10.1016/j.pediatrneurol.2010.11.007. PMID: 21397166
Tepper VJ, Farley JJ, Rothman MI, Houck DL, Davis KF, Collins-Jones TL, Wachtel RC
Pediatrics 1998 Mar;101(3):E7. doi: 10.1542/peds.101.3.e7. PMID: 9493492

Prognosis

Gilani A, Adang LA, Vanderver A, Collins A, Kleinschmidt-DeMasters BK
Pediatr Dev Pathol 2019 Nov-Dec;22(6):566-570. Epub 2019 Apr 5 doi: 10.1177/1093526619837797. PMID: 30952201Free PMC Article
Rosti RO, Dikoglu E, Zaki MS, Abdel-Salam G, Makhseed N, Sese JC, Musaev D, Rosti B, Harbert MJ, Jones MC, Vaux KK, Gleeson JG
Am J Med Genet A 2016 Apr;170A(4):992-8. Epub 2016 Jan 5 doi: 10.1002/ajmg.a.37533. PMID: 27001912Free PMC Article
Poulton C, Oegema R, Heijsman D, Hoogeboom J, Schot R, Stroink H, Willemsen MA, Verheijen FW, van de Spek P, Kremer A, Mancini GM
Neurogenetics 2013 Feb;14(1):43-51. Epub 2012 Dec 9 doi: 10.1007/s10048-012-0351-8. PMID: 23224214
Frydman M, Jager-Roman E, de Vries L, Stoltenburg-Didinger G, Nussinovitch M, Sirota L
Am J Med Genet 1993 Aug 1;47(1):31-6. doi: 10.1002/ajmg.1320470107. PMID: 8368248
Billard C, Dulac O, Bouloche J, Echenne B, Lebon P, Motte J, Robain O, Santini JJ
Neuropediatrics 1989 Feb;20(1):12-9. doi: 10.1055/s-2008-1071258. PMID: 2654691

Clinical prediction guides

Ivanov I, Pacheva I, Yordanova R, Sotkova I, Galabova F, Gaberova K, Panova M, Gheneva I, Tsvetanova T, Noneva K, Dimitrova D, Markov S, Sapundzhiev N, Bichev S, Savov A
CNS Neurol Disord Drug Targets 2023;22(2):207-214. doi: 10.2174/1871527321666220221100704. PMID: 35189806
Wong KM, Jepsen WM, Efthymiou S, Salpietro V, Sanchez-Castillo M, Yip J, Kriouile Y, Diegmann S, Dreha-Kulaczewski S, Altmüller J, Thiele H, Nürnberg P, Toosi MB, Akhondian J, Ghayoor Karimiani E, Hummel-Abmeier H, Huppke B, Houlden H, Gärtner J, Maroofian R, Huppke P
Brain 2022 Sep 14;145(9):3022-3034. doi: 10.1093/brain/awac154. PMID: 35759269
O'Brien A, Marshall CR, Blaser S, Ray PN, Yoon G
Eur J Hum Genet 2017 Jun;25(6):775-778. Epub 2017 Apr 5 doi: 10.1038/ejhg.2017.39. PMID: 28378817Free PMC Article
Tohyama J, Nakashima M, Nabatame S, Gaik-Siew C, Miyata R, Rener-Primec Z, Kato M, Matsumoto N, Saitsu H
J Hum Genet 2015 Apr;60(4):167-73. Epub 2015 Jan 29 doi: 10.1038/jhg.2015.5. PMID: 25631096
Tohyama J, Akasaka N, Osaka H, Maegaki Y, Kato M, Saito N, Yamashita S, Ohno K
Brain Dev 2008 May;30(5):349-55. Epub 2007 Dec 11 doi: 10.1016/j.braindev.2007.10.006. PMID: 18065176

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