Rare Oncology News

Disease Profile

X-linked intellectual disability, Najm type

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

Q04.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

rnn-xlinkeddominant.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

X-linked intellectual disability microcephaly pontocerebellar hypoplasia; MICPCH; Intellectual disability and microcephaly with pontine and cerebellar hypoplasia ;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 163937

Definition
Najm type X-linked intellectual deficit is a rare cerebellar dysgenesis syndrome characterized by variable clinical manifestations ranging from mild intellectual deficit with or without congenital nystagmus, to severe cognitive impairment associated with cerebellar and pontine hypoplasia/atrophy and abnormalities of cortical development.

Epidemiology
Prevalence of this rare neurological syndrome is unknown. Up to 35 families have been reported to date.

Clinical description
Patients (mostly females) have been reported to have variable clinical manifestations including intellectual deficit, severe developmental delay, seizures, unsteady gait, sensorineural hearing loss and postnatal microcephaly (in most cases). Minor facial anomalies include: low or broad forehead, hypertelorism, long philtrum and micrognathia. Ocular findings are also variable and include congenital nystagmus, strabismus, cataracts, myopia or reduced visual acuity. Males appear to be more severely affected.

Etiology
Point mutations and deletions in the CASK gene (Xp11.4) have been found in patients with this syndrome.

Diagnostic methods
Magnetic resonance imaging (MRI) generally shows pontocerebellar hypoplasia/atrophy and simplified cortical gyri. Molecular genetic testing is needed to confirm diagnosis.

Genetic counseling
Transmission follows an X-linked dominant pattern.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Intellectual disability, moderate
IQ between 34 and 49
0002342
Severe global developmental delay
0011344
30%-79% of people have these symptoms
Broad forehead
Increased width of the forehead
Wide forehead

[ more ]

0000337
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Long philtrum
0000343
Macrotia
Large ears
0000400
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Seizure
0001250
Sensorineural hearing impairment
0000407
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
5%-29% of people have these symptoms
Absent speech
Absent speech development
Lack of language development
Lack of speech
No speech development
No speech or language development
Nonverbal

[ more ]

0001344
Chorioretinal coloboma
Birth defect that causes a hole in the innermost layer at the back of the eye
0000567
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Macrogyria
0007227
Optic atrophy
0000648
Optic disc pallor
0000543
Optic nerve hypoplasia
0000609
Rigidity
Muscle rigidity
0002063
Scoliosis
0002650
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Percent of people who have these symptoms is not available through HPO
Abnormally large globe
Increased size of eyes
Large eyes

[ more ]

0001090
Broad nasal tip
Broad tip of nose
Broad, upturned nose
Increased breadth of nasal tip
Increased breadth of tip of nose
Increased width of nasal tip
Increased width of tip of nose
Nasal tip, broad
Nasal tip, wide
Wide tip of nose

[ more ]

0000455
Decreased body weight
Decreased weight
Low body weight
Low weight
Weight less than 3rd percentile

[ more ]

0004325
Dilated fourth ventricle
0002198
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Hyperreflexia
Increased reflexes
0001347
Hypohidrosis
Decreased ability to sweat
Decreased sweating
Sweating, decreased

[ more ]

0000966
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Oval face
Oval facial shape
0000300
Postnatal growth retardation
Growth delay as children
0008897
Progressive microcephaly
Progressively abnormally small cranium
Progressively abnormally small skull

[ more ]

0000253
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge

[ more ]

0000426
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Short stature
Decreased body height
Small stature

[ more ]

0004322
X-linked dominant inheritance
0001423

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss X-linked intellectual disability, Najm type. Click on the link to view a sample search on this topic.