AP-4-Associated Hereditary Spastic Paraplegia

Title

Other Names:

Severe intellectual disability and progressive spastic paraplegia; AP4 deficiency syndrome; Adaptor Protein Complex 4 Deficiency; Severe intellectual disability and progressive spastic paraplegia; AP4 deficiency syndrome; Adaptor Protein Complex 4 Deficiency; AP-4 Deficiency; AP-4-Associated HSP; AP-4 Deficiency Syndrome See More

Subtypes:

Spastic paraplegia 47; Spastic paraplegia 51

Summary Summary

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

Orpha Number: 280763

Definition

Severe intellectual disability and progressive spastic paraplegia is a rare complex spastic paraplegia characterized by an early onset hypotonia that progresses to spasticity, global developmental delay, severe intellectual disability and speech impairment, microcephaly, short stature and dysmorphic features. Patients often become non-ambulatory, and some develop seizures and stereotypic laughter.

Visit the Orphanet disease page for more resources.

Last updated: 8/1/2018

Symptoms 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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Progressive spastic paraplegia		0007020
30%-79% of people have these symptoms
Cerebral cortical atrophy	Decrease in size of the outer layer of the brain due to loss of brain cells	0002120
Difficulty walking	Difficulty in walking	0002355
Dystonia		0001332
Poor speech		0002465
Spastic dysarthria		0002464
Waddling gait	'Waddling' gait Waddling walk [ more ]	0002515
5%-29% of people have these symptoms
Abnormality of the periventricular white matter		0002518
Everted upper lip vermilion	Outward turned upper lip	0010803
Febrile seizure (within the age range of 3 months to 6 years)	Fever induced seizures	0002373
Focal-onset seizure	Seizure affecting one half of brain	0007359
Genu recurvatum	Back knee Knee hyperextension [ more ]	0002816
High palate	Elevated palate Increased palatal height [ more ]	0000218
Overweight		0025502
Pes planus	Flat feet Flat foot [ more ]	0001763
Short stature	Decreased body height Small stature [ more ]	0004322
Shyness		0100962
Stereotypy	Repetitive movements Repetitive or self-injurious behavior [ more ]	0000733
Talipes equinovarus	Club feet Club foot Clubfeet Clubfoot [ more ]	0001762
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
1%-4% of people have these symptoms
Acetabular dysplasia		0008807
Amblyopia	Lazy eye Wandering eye [ more ]	0000646
Generalized joint laxity	Hypermobility of all joints	0002761
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Percent of people who have these symptoms is not available through HPO
Adducted thumb	Inward turned thumb	0001181
Autosomal recessive inheritance		0000007
Babinski sign		0003487
Bulbous nose		0000414
Cerebellar atrophy	Degeneration of cerebellum	0001272
Cerebral palsy		0100021
Coarse facial features	Coarse facial appearance	0000280
Congenital onset	Symptoms present at birth	0003577
Decreased muscle mass		0003199
Delayed speech and language development	Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ]	0000750
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Drooling	Dribbling	0002307
Dysarthria	Difficulty articulating speech	0001260
Facial hypotonia	Decreased facial muscle tone Low facial muscle tone Reduced facial muscle tone [ more ]	0000297
Flexion contracture	Flexed joint that cannot be straightened	0001371
Gliosis		0002171
Global developmental delay		0001263
Hyperreflexia	Increased reflexes	0001347
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Hypoplasia of the corpus callosum	Underdevelopment of part of brain called corpus callosum	0002079
Inability to walk		0002540
Intellectual disability, progressive	Mental retardation, progressive Progressive mental retardation [ more ]	0006887
Intellectual disability, severe	Early and severe mental retardation Mental retardation, severe Severe mental retardation [ more ]	0010864
Long nose	Elongated nose Increased height of nose Increased length of nose Increased nasal height Increased nasal length Nasal elongation [ more ]	0003189
Loss of ability to walk		0006957
Mandibular prognathia	Big lower jaw Increased projection of lower jaw Increased size of lower jaw Large lower jaw Prominent chin Prominent lower jaw [ more ]	0000303
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Muscular hypotonia of the trunk	Low muscle tone in trunk	0008936
Narrow face	Decreased breadth of face Decreased width of face [ more ]	0000275
Narrow forehead	Decreased width of the forehead	0000341
Neonatal hypotonia	Low muscle tone, in neonatal onset	0001319
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Pointed chin	Pointy chin Small pointed chin Witch's chin [ more ]	0000307
Prominent antihelix		0000395
Prominent nose	Big nose Disproportionately large nose Increased nasal size Increased size of nose Large nose Pronounced nose [ more ]	0000448
Pseudobulbar signs		0002200
Seizure		0001250
Short philtrum		0000322
Slow progression	Signs and symptoms worsen slowly with time	0003677
Spastic paraplegia		0001258
Spastic tetraplegia		0002510
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
Thick vermilion border	Full lips Increased volume of lip Plump lips Prominent lips Thick lips [ more ]	0012471
Ventriculomegaly		0002119
Wide mouth	Broad mouth Large mouth [ more ]	0000154
Wide nasal ridge	Increased width of nasal ridge	0012811

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Last updated: 7/1/2020

Learn More 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

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
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.
Online Mendelian Inheritance in Man (OMIM)
Online Mendelian Inheritance in Man (OMIM)
Online Mendelian Inheritance in Man (OMIM)
Online Mendelian Inheritance in Man (OMIM)
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

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