Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

Developmental and epileptic encephalopathy, 1(DEE1)

MedGen UID:: 483052
•Concept ID:: C3463992
•: Disease or Syndrome

Synonyms:	DEE1; Epileptic encephalopathy, early infantile, 1; INFANTILE SPASM SYNDROME, X-LINKED 1; OHTAHARA SYNDROME, X-LINKED; Tonic spasms with clustering, arrest of psychomotor development and hypsarrhythmia on EEG; West's syndrome; X-Linked Infantile Spasm Syndrome; X-linked infantile spasms

Gene (location): Gene(s) directly associated with this condition or phenotype.	ARX (Xp21.3)

Monarch Initiative:	MONDO:0010632
OMIM®:	308350

Definition

Developmental and epileptic encephalopathy-1 (DEE1) is a severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Approximately 75% of DEE1 patients progress to tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG (Kato et al., 2007). DEE1 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (DEE) to syndromic (309510) and nonsyndromic (300419) mental retardation. Although males with ARX mutations are often more severely affected, female mutation carriers may also be affected (Kato et al., 2004; Wallerstein et al., 2008). Reviews Deprez et al. (2009) reviewed the genetics of epilepsy syndromes starting in the first year of life and included a diagnostic algorithm. Genetic Heterogeneity of Developmental and Epileptic Encephalopathy Also see DEE2 (300672), caused by mutation in the CDKL5 gene (300203); DEE3 (609304), caused by mutation in the SLC25A22 gene (609302); DEE4 (612164), caused by mutation in the STXBP1 gene (602926); DEE5 (613477), caused by mutation in the SPTAN1 gene (182810); DEE6A (607208), also known as Dravet syndrome, caused by mutation in the SCN1A gene (182389); DEE6B (619317), also caused by mutation in the SCN1A gene; DEE7 (613720), caused by mutation in the KCNQ2 gene (602235); DEE8 (300607), caused by mutation in the ARHGEF9 gene (300429); DEE9 (300088), caused by mutation in the PCDH19 gene (300460); DEE10 (613402), caused by mutation in the PNKP gene (605610); DEE11 (613721), caused by mutation in the SCN2A gene (182390); DEE12 (613722), caused by mutation in the PLCB1 gene (607120); DEE13 (614558), caused by mutation in the SCN8A gene (600702); DEE14 (614959), caused by mutation in the KCNT1 gene (608167); DEE15 (615006), caused by mutation in the ST3GAL3 gene (606494); DEE16 (615338), caused by mutation in the TBC1D24 gene (613577); DEE17 (615473), caused by mutation in the GNAO1 gene (139311); DEE18 (615476), caused by mutation in the SZT2 gene (615463); DEE19 (615744), caused by mutation in the GABRA1 gene (137160); DEE20 (300868), caused by mutation in the PIGA gene (311770); DEE21 (615833), caused by mutation in the NECAP1 gene (611623); DEE22 (300896), caused by mutation in the SLC35A2 gene (314375); DEE23 (615859), caused by mutation in the DOCK7 gene (615730); DEE24 (615871), caused by mutation in the HCN1 gene (602780); DEE25 (615905), caused by mutation in the SLC13A5 gene (608305); DEE26 (616056), caused by mutation in the KCNB1 gene (600397); DEE27 (616139), caused by mutation in the GRIN2B gene (138252); DEE28 (616211), caused by mutation in the WWOX gene (605131); DEE29 (616339), caused by mutation in the AARS gene (601065); DEE30 (616341), caused by mutation in the SIK1 gene (605705); DEE31A (616346) and DEE31B (620352), caused by mutation in the DNM1 gene (602377); DEE32 (616366), caused by mutation in the KCNA2 gene (176262); DEE33 (616409), caused by mutation in the EEF1A2 gene (602959); DEE34 (616645), caused by mutation in the SLC12A5 gene (606726); DEE35 (616647), caused by mutation in the ITPA gene (147520); DEE36 (300884), caused by mutation in the ALG13 gene (300776); DEE37 (616981), caused by mutation in the FRRS1L gene (604574); DEE38 (617020), caused by mutation in the ARV1 gene (611647); DEE39 (612949), caused by mutation in the SLC25A12 gene (603667); DEE40 (617065), caused by mutation in the GUF1 gene (617064); DEE41 (617105), caused by mutation in the SLC1A2 gene (600300); DEE42 (617106), caused by mutation in the CACNA1A gene (601011); DEE43 (617113), caused by mutation in the GABRB3 gene (137192); DEE44 (617132), caused by mutation in the UBA5 gene (610552); DEE45 (617153), caused by mutation in the GABRB1 gene (137190); DEE46 (617162), caused by mutation in the GRIN2D gene (602717); DEE47 (617166), caused by mutation in the FGF12 gene (601513); DEE48 (617276), caused by mutation in the AP3B2 gene (602166); DEE49 (617281), caused by mutation in the DENND5A gene (617278); DEE50 (616457) caused by mutation in the CAD gene (114010); DEE51 (617339), caused by mutation in the MDH2 gene (154100); DEE52 (617350), caused by mutation in the SCN1B gene (600235); DEE53 (617389), caused by mutation in the SYNJ1 gene (604297); DEE54 (617391), caused by mutation in the HNRNPU gene (602869); DEE55 (617599), caused by mutation in the PIGP gene (605938); DEE56 (617665), caused by mutation in the YWHAG gene (605356); DEE57 (617771), caused by mutation in the KCNT2 gene (610044); DEE58 (617830), caused by mutation in the NTRK2 gene (600456); DEE59 (617904), caused by mutation in the GABBR2 gene (607340); DEE60 (617929), caused by mutation in the CNPY3 gene (610774); DEE61 (617933), caused by mutation in the ADAM22 gene (603709); DEE62 (617938), caused by mutation in the SCN3A gene (182391); DEE63 (617976), caused by mutation in the CPLX1 gene (605032); DEE64 (618004), caused by mutation in the RHOBTB2 gene (607352); DEE65 (618008), caused by mutation in the CYFIP2 gene (606323); DEE66 (618067), caused by mutation in the PACS2 gene (610423); DEE67 (618141), caused by mutation in the CUX2 gene (610648); DEE68 (618201), caused by mutation in the TRAK1 gene (608112); DEE69 (618285), caused by mutation in the CACNA1E gene (601013); DEE70 (618298) caused by mutation in the PHACTR1 gene (608723); DEE71 (618328), caused by mutation in the GLS gene (138280); DEE72 (618374), caused by mutation in the NEUROD2 gene (601725); DEE73 (618379), caused by mutation in the RNF13 gene (609247); DEE74 (618396), caused by mutation in the GABRG2 gene (137164); DEE75 (618437), caused by mutation in the PARS2 gene (612036); DEE76 (618468), caused by mutation in the ACTL6B gene (612458); DEE77 (618548), caused by mutation in the PIGQ gene (605754); DEE78 (618557), caused by mutation in the GABRA2 gene (137140); DEE79 (618559), caused by mutation in the GABRA5 gene (137142); DEE80 (618580), caused by mutation in the PIGB gene (604122); DEE81 (618663), caused by mutation in the DMXL2 gene (612186); DEE82 (618721), caused by mutation in the GOT2 gene (138150); DEE83 (618744), caused by mutation in the UGP2 gene (191760); DEE84 (618792), caused by mutation in the UGDH gene (603370); DEE85 (301044), caused by mutation in the SMC1A gene (300040); DEE86 (618910), caused by mutation in the DALRD3 gene (618904); DEE87 (618916), caused by mutation in the CDK19 gene (614720); DEE88 (618959), caused by mutation in the MDH1 gene (152400); DEE89 (619124), caused by mutation in the GAD1 gene (605363); DEE90 (301058), caused by mutation in the FGF13 gene (300070); DEE91 (617711), caused by mutation in the PPP3CA gene (114105); DEE92 (617829), caused by mutation in the GABRB2 gene (600232); DEE93 (618012), caused by mutation in the ATP6V1A gene (607027); DEE94 (615369), caused by mutation in the CHD2 gene (602119); DEE95 (618143), caused by mutation in the PIGS gene (610271); DEE96 (619340), caused by mutation in the NSF gene (601633); DEE97 (619561), caused by mutation in the iCELF2 gene (602538); DEE98 (619605), caused by mutation in the ATP1A2 gene (182340); DEE99 (619606), caused by mutation in the ATP1A3 gene (182350); DEE100 (619777), caused by mutation in the FBXO28 gene (609100); DEE101 (619814), caused by mutation in the GRIN1 gene (138249); DEE102 (619881), caused by mutation in the SLC38A3 gene (604437); DEE103 (619913), caused by mutation in the KCNC2 gene (176256); DEE104 (619970), caused by mutation in the ATP6V0A1 gene (192130); DEE105 (619983), caused by mutation in the HID1 gene (605752); DEE106 (620028), caused by mutation in the UFSP2 gene (611482); DEE107 (620033), caused by mutation in the NAPB gene ( [from OMIM]

Additional description

From MedlinePlus Genetics
Most babies with DEE1 have characteristic results on an electroencephalogram (EEG), a test used to measure the electrical activity of the brain. The EEG of these individuals typically shows an irregular pattern known as hypsarrhythmia, and this finding can help differentiate infantile spasms from other types of seizures.

Early in life, babies with DEE1 stop developing normally and begin to lose skills they have acquired (developmental regression), such as sitting, rolling over, and babbling. Most affected individuals also have intellectual disability throughout their lives.

Developmental and epileptic encephalopathy 1 (DEE1) is a seizure disorder characterized by a type of seizure known as infantile spasms. The spasms usually appear before the age of 1. Several types of spasms have been described, but the most commonly reported type involves bending at the waist and neck and extending the arms and legs (sometimes called a jackknife spasm). Each spasm lasts only seconds, but they occur in clusters several minutes long. Although individuals do not usually have spasms while they are sleeping, the spasms commonly occur just after awakening. Infantile spasms usually stop by age 5, but many children then develop other types of seizures that recur throughout their lives. https://medlineplus.gov/genetics/condition/developmental-and-epileptic-encephalopathy-1

Clinical features

From HPO

Micropenis

MedGen UID:: 1633603
•Concept ID:: C4551492
•: Congenital Abnormality

Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.

See: Feature record | Search on this feature

Growth delay

MedGen UID:: 99124
•Concept ID:: C0456070
•: Pathologic Function

A deficiency or slowing down of growth pre- and postnatally.

See: Feature record | Search on this feature

Dysphagia

MedGen UID:: 41440
•Concept ID:: C0011168
•: Disease or Syndrome

Difficulty in swallowing.

See: Feature record | Search on this feature

Dyskinesia

MedGen UID:: 8514
•Concept ID:: C0013384
•: Disease or Syndrome

A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.

See: Feature record | Search on this feature

Dystonic disorder

MedGen UID:: 3940
•Concept ID:: C0013421
•: Sign or Symptom

An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.

See: Feature record | Search on this feature

Focal motor seizure

MedGen UID:: 5237
•Concept ID:: C0016399
•: Disease or Syndrome

A type of focal-onset seizure characterized by a motor sign as its initial semiological manifestation.

See: Feature record | Search on this feature

Choreoathetosis

MedGen UID:: 39313
•Concept ID:: C0085583
•: Disease or Syndrome

Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).

See: Feature record | Search on this feature

Hyperreflexia

MedGen UID:: 57738
•Concept ID:: C0151889
•: Finding

Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.

See: Feature record | Search on this feature

Abnormal pyramidal sign

MedGen UID:: 68582
•Concept ID:: C0234132
•: Sign or Symptom

Functional neurological abnormalities related to dysfunction of the pyramidal tract.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Tonic seizure

MedGen UID:: 82855
•Concept ID:: C0270844
•: Disease or Syndrome

A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening.

See: Feature record | Search on this feature

Epileptic encephalopathy

MedGen UID:: 452596
•Concept ID:: C0543888
•: Disease or Syndrome

A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Spastic tetraparesis

MedGen UID:: 658719
•Concept ID:: C0575059
•: Disease or Syndrome

Spastic weakness affecting all four limbs.

See: Feature record | Search on this feature

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).

See: Feature record | Search on this feature

Focal-onset seizure

MedGen UID:: 199670
•Concept ID:: C0751495
•: Disease or Syndrome

A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.

See: Feature record | Search on this feature

Reduced eye contact

MedGen UID:: 303190
•Concept ID:: C1445953
•: Finding

A reduced frequency or duration of eye contact.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Ventriculomegaly

MedGen UID:: 480553
•Concept ID:: C3278923
•: Finding

An increase in size of the ventricular system of the brain.

See: Feature record | Search on this feature

Intellectual disability

MedGen UID:: 811461
•Concept ID:: C3714756
•: Mental or Behavioral Dysfunction

Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

See: Feature record | Search on this feature

Infantile spasms

MedGen UID:: 854616
•Concept ID:: C3887898
•: Disease or Syndrome

Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).

See: Feature record | Search on this feature

Delayed CNS myelination

MedGen UID:: 867393
•Concept ID:: C4021758
•: Anatomical Abnormality

Delayed myelination in the central nervous system.

See: Feature record | Search on this feature

Generalized myoclonic seizure

MedGen UID:: 892704
•Concept ID:: C4021759
•: Disease or Syndrome

A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.

See: Feature record | Search on this feature

Erratic myoclonus

MedGen UID:: 1370221
•Concept ID:: C4476727
•: Sign or Symptom

A type of myoclonus in which the myoclonias shift from body region to another in a random and asynchronous fashion. Erratic myoclonus can affect the face or limbs, are brief, single or repetitive, very frequent and nearly continuous.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Plagiocephaly

MedGen UID:: 78562
•Concept ID:: C0265529
•: Congenital Abnormality

Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.

See: Feature record | Search on this feature

Poor head control

MedGen UID:: 322809
•Concept ID:: C1836038
•: Finding

Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.

See: Feature record | Search on this feature

Axial hypotonia

MedGen UID:: 342959
•Concept ID:: C1853743
•: Finding

Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

See: Feature record | Search on this feature

Microcephaly

MedGen UID:: 1644158
•Concept ID:: C4551563
•: Finding

Head circumference below 2 standard deviations below the mean for age and gender.

See: Feature record | Search on this feature

Dyspnea

MedGen UID:: 3938
•Concept ID:: C0013404
•: Sign or Symptom

Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.

See: Feature record | Search on this feature

Microphthalmia

MedGen UID:: 10033
•Concept ID:: C0026010
•: Congenital Abnormality

Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.

See: Feature record | Search on this feature

Show all Hide all

Abnormality of the digestive system
- Dysphagia
Abnormality of the eye
- Microphthalmia
Abnormality of the genitourinary system
- Micropenis
Abnormality of the musculoskeletal system
Abnormality of the nervous system
Abnormality of the respiratory system
- Dyspnea
Growth abnormality
- Growth delay

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVDevelopmental and epileptic encephalopathy, 1

ARX-related epileptic encephalopathy
- Infantile epileptic dyskinetic encephalopathy
  - Developmental and epileptic encephalopathy, 1

Professional guidelines

PubMed

Clinical features and genotype-phenotype correlations in epilepsy patients with de novo DYNC1H1 variants.

Cuccurullo C, Cerulli Irelli E, Ugga L, Riva A, D'Amico A, Cabet S, Lesca G, Bilo L, Zara F, Iliescu C, Barca D, Fung F, Helbig K, Ortiz-Gonzalez X, Schelhaas HJ, Willemsen MH, van der Linden I, Canafoglia L, Courage C, Gommaraschi S, Gonzalez-Alegre P, Bardakjian T, Syrbe S, Schuler E, Lemke JR, Vari S, Roende G, Bak M, Huq M, Powis Z, Johannesen KM, Hammer TB, Møller RS, Rabin R, Pappas J, Zupanc ML, Zadeh N, Cohen J, Naidu S, Krey I, Saneto R, Thies J, Licchetta L, Tinuper P, Bisulli F, Minardi R, Bayat A, Villeneuve N, Molinari F, Salimi Dafsari H, Moller B, Le Roux M, Houdayer C, Vecchi M, Mammi I, Fiorini E, Proietti J, Ferri S, Cantalupo G, Battaglia DI, Gambardella ML, Contaldo I, Brogna C, Trivisano M, De Dominicis A, Bova SM, Gardella E, Striano P, Coppola A
Epilepsia 2024 Sep;65(9):2728-2750. Epub 2024 Jul 2 doi: 10.1111/epi.18054. PMID: 38953796

See all (1)

Recent clinical studies

Prognosis

Population-based study of rare epilepsy incidence in a US urban population.

Barbour K, Tian N, Yozawitz EG, Wolf S, McGoldrick PE, Sands TT, Nelson A, Basma N, Grinspan ZM
Epilepsia 2024 Aug;65(8):2341-2353. Epub 2024 May 25 doi: 10.1111/epi.18029. PMID: 38795333 Free PMC Article

See all (1)

MedGen

National Center for Biotechnology Information

Send to:

Developmental and epileptic encephalopathy, 1(DEE1)

Definition

Additional description

Clinical features

Term Hierarchy

Professional guidelines

PubMed

Recent clinical studies

Prognosis

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

Reviews

Related information

Recent activity