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SLC35A2-congenital disorder of glycosylation(CDG2M; CDGIIm; EIEE22; DEE22)

MedGen UID:
813018
Concept ID:
C3806688
Disease or Syndrome
Synonyms: CDG IIm; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIm; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIm, SOMATIC MOSAIC; DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 22; EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 22; SLC35A2-CDG
SNOMED CT: SLC35A2-CDG - solute carrier family 35 member A2 congenital disorder of glycosylation (771516000); Congenital disorder of glycosylation type 2m (771516000); Congenital disorder of glycosylation type IIm (771516000); Solute carrier family 35 member A2 congenital disorder of glycosylation (771516000); CDG2M - congenital disorder of glycosylation type 2m (771516000)
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
 
Gene (location): SLC35A2 (Xp11.23)
 
Monarch Initiative: MONDO:0010478
OMIM®: 300896
Orphanet: ORPHA356961

Definition

Congenital disorder of glycosylation type IIm, or developmental and epileptic encephalopathy-22 (DEE22), is an X-linked dominant severe neurologic disorder characterized by infantile-onset seizures, hypsarrhythmia on EEG, hypotonia, and developmental delay associated with severe intellectual disability and lack of speech. These features are consistent with developmental and epileptic encephalopathy (DEE). Brain malformations usually include cerebral and cerebellar atrophy. Additionally, some patients may have dysmorphic features or coarse facies (Ng et al., 2013; Kodera et al., 2013). For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Additional description

From MedlinePlus Genetics
SLC35A2-congenital disorder of glycosylation (SLC35A2-CDG, formerly known as congenital disorder of glycosylation type IIm) is an inherited condition that causes neurological problems and other abnormalities. This disorder's signs and symptoms and their severity vary among affected individuals.

Individuals with SLC35A2-CDG typically develop signs and symptoms of the condition early in infancy. Seizures develop within the first months of life, usually involving uncontrollable muscle stiffening (infantile spasms) that can switch to shorter episodes of muscle jerks (epileptic spasms) later in childhood. In some individuals, the seizures do not improve with anti-epileptic medications. Individuals with SLC35A2-CDG often have abnormal brain function (encephalopathy), unusual facial features, skeletal abnormalities, and weak muscle tone (hypotonia) with poor head control. They also have severe intellectual disability and delayed development, often only being able to sit or crawl and never developing meaningful speech. Affected children may have feeding difficulties and fail to grow or gain weight at the expected rate. Some have vision or hearing problems.

In SLC35A2-CDG, medical imaging shows loss of tissue (atrophy) in parts of the brain called the cerebrum and cerebellum. These brain regions are necessary for thinking ability, hearing, vision, emotion, and coordinated movement. There can also be thinning of the tissue that connects the left and right halves of the brain (the corpus callosum) or a fluid-filled sac (cyst) on the membrane that surrounds the brain (arachnoid pouch).  https://medlineplus.gov/genetics/condition/slc35a2-congenital-disorder-of-glycosylation

Clinical features

From HPO
Vesicovaginal fistula
MedGen UID:
22640
Concept ID:
C0042582
Anatomical Abnormality
The presence of a fistula connecting the urinary bladder to the vagina.
Ureteropelvic junction obstruction
MedGen UID:
105482
Concept ID:
C0521619
Anatomical Abnormality
Blockage of urine flow from the renal pelvis to the proximal ureter.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
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.
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.
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.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
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.
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.
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).
Epileptic spasm
MedGen UID:
315948
Concept ID:
C1527366
Disease or Syndrome
A sudden flexion, extension, or mixed extension-flexion of predominantly proximal and truncal muscles that is usually more sustained than a myoclonic movement but not as sustained as a tonic seizure. Limited forms may occur
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Lateral ventricle dilatation
MedGen UID:
383904
Concept ID:
C1856409
Pathologic Function
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.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
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.
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting.
Enlarged cisterna magna
MedGen UID:
344031
Concept ID:
C1853377
Finding
Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Neonatal hyperbilirubinemia
MedGen UID:
208991
Concept ID:
C0857007
Disease or Syndrome
A type of hyperbilirubinemia with neonatal onset.
Abnormal isoelectric focusing of serum transferrin
MedGen UID:
413671
Concept ID:
C2749688
Finding
Glycosylated transferrin concentrations can be measured in serum as a marker of N-linked glycosylation fidelity. In the traditional nomenclature for congenital disorders of glycosylation, absence of entire glycans was designated type I, and loss of one or more monosaccharides as type II. These terms are retained for historical reasons but for new annotations the precise glycosylation defect should be recorded.
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Teeth, fused
MedGen UID:
4808
Concept ID:
C0016873
Congenital Abnormality
The union of two separately developing tooth germs typically leading to one less tooth than normal in the affected dental arch.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Thick vermilion border
MedGen UID:
332232
Concept ID:
C1836543
Finding
Increased width of the skin of vermilion border region of upper lip.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Exaggerated cupid bow
MedGen UID:
376842
Concept ID:
C1850629
Finding
More pronounced paramedian peaks and median notch of the Cupid's bow.
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
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.
Ocular flutter
MedGen UID:
115965
Concept ID:
C0234650
Finding
Ocular flutter is an abnormal eye movement consisting of repetitive, irregular, involuntary bursts of horizontal saccades without an intersaccadic interval. It is generally superimposed on normal oculomotor behavior and its occurrence may be favored by various events, such as blinks, the triggering of normal saccades or optokinetic stimulation.
Rod-cone dystrophy
MedGen UID:
1632921
Concept ID:
C4551714
Disease or Syndrome
An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSLC35A2-congenital disorder of glycosylation
Follow this link to review classifications for SLC35A2-congenital disorder of glycosylation in Orphanet.

Recent clinical studies

Clinical prediction guides

Witters P, Tahata S, Barone R, Õunap K, Salvarinova R, Grønborg S, Hoganson G, Scaglia F, Lewis AM, Mori M, Sykut-Cegielska J, Edmondson A, He M, Morava E
Genet Med 2020 Jun;22(6):1102-1107. Epub 2020 Feb 27 doi: 10.1038/s41436-020-0767-8. PMID: 32103184Free PMC Article

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