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Disease Profile

GAPO syndrome

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

Neonatal

ICD-10

Q87.8

Inheritance

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

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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

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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.

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

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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.

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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.

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Not applicable

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Other names (AKA)

Growth retardation, Alopecia, Pseudoanodontia and Optic atrophy

Categories

Congenital and Genetic Diseases; Eye diseases; Mouth Diseases;

Summary

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

Orpha Number: 2067

Definition
A multiple congenital anomalies (MCA) syndrome involving connective tissue characterized by Growth retardation, Alopecia, Pseudoanodontia and Ocular manifestations.

Epidemiology
Approximately 38 patients have been reported in literature since the first description in 1947.

Clinical description
Patients have a short stature due to post-natal growth retardation and a typical facies with high and bossing forehead, hypertelorism, puffy eyelids, midfacial hypoplasia, depressed nasal bridge, anteverted wide nostrils, thick everted lower lip, micrognathia, low-set ears and premature aging appearance mainly due to redundant hyperelastic skin with unusual wrinkles. Scalp hair may be primarily present but disappears after the first months of life leading to complete or partial alopecia. Eyebrows and/or eyelashes are sparse. Primary and permanent teeth are formed but fail to erupt. Ocular manifestations may include progressive optic atrophy, glaucoma, strabismus, megalocornea, myelinated retinal nerve fiber layer, bilateral keratoconus, nystagmus and ptosis. Otorhinolaryngologic features are choanal atresia, deafness and presence of flaccid and pulsatile masses with an audible murmur in the mastoid area associated with dilated and tortuous scalp veins. Patients have a mild intellectual deficit. Some patients have also been reported with umbilical hernia, hyperextensible joints, osseous anomalies (congenital dislocation of hips or delayed bone age) and cutaneous manifestations (hemangioma or depigmented areas). Other manifestations include intracranial hypertension in infancy, hypothyroidism, mitral valve dysfunction or cardiomyopathy, hepatomegaly, renal impairment and altered gonadal functions (irregular periods or amenorrhea, oligoastenospermia).

Etiology
Homozygous nonsense or splicing mutations in the ANTXR1 gene, encoding anthrax toxin receptor 1, also known as tumor endothelial marker 8 (TEM8) cause GAPO Syndrome.

Diagnostic methods
Diagnosis mostly relies on physical examination. Cerebral angiography and magnetic resonance angiography reveal prominent cortical veins, occluded or absent left transverse sinus, left sigmoid sinus, agenesis of left jugular vein, and enlarged veins underlying the palpable scalp masses. Skin biopsy may reveal dermis anomalies including amorphous hyaline substance and recently reported pyoderma vegetans.

Antenatal diagnosis
Antenatal diagnosis is not possible as features are not detectable by fetal ultrasound.

Genetic counseling
GAPO syndrome appears to have an autosomal recessive transmission pattern.

Management and treatment
There is no curative treatment. Management mostly relies on ophthalmologic surveillance and symptomatic treatment of the multiple health problems.

Prognosis
GAPO patients are reported to have a reduced lifespan (until their 4th -6th decade of life).

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
Alopecia
Hair loss
0001596
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Broad forehead
Increased width of the forehead
Wide forehead

[ more ]

0000337
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Early balding
0002234
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

0000232
Frontal bossing
0002007
High forehead
0000348
Hyperextensible skin
Hyperelastic skin
Skin hyperelasticity
Stretchable skin

[ more ]

0000974
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Long philtrum
0000343
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Palpebral edema
Fullness of eyelids
Puffy eyelids
Puffy lids
Swelling of eyelids

[ more ]

0100540
Prematurely aged appearance
Precociously senile appearance
0007495
Short stature
Decreased body height
Small stature

[ more ]

0004322
Sparse and thin eyebrow
Thin, sparse eyebrows
0000535
Sparse eyelashes
Scant eyelashes
Scanty eyelashes
Thin eyelashes

[ more ]

0000653
Thick nasal alae
0009928
Underdeveloped supraorbital ridges
Flattened bony protrusion above eyes
0009891
30%-79% of people have these symptoms
Abnormal clavicle morphology
Abnormal collarbone
0000889
Abnormal form of the vertebral bodies
0003312
Abnormal palate morphology
Abnormality of the palate
Abnormality of the roof of the mouth

[ more ]

0000174
Abnormality of pelvic girdle bone morphology
Abnormal shape of pelvic girdle bone
0002644
Abnormality of the cerebral vasculature
Abnormality of the cerebral blood vessels
0100659
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Glaucoma
0000501
Keratoconus
Bulging cornea
0000563
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
Skin tags
0010609
Umbilical hernia
0001537
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
5%-29% of people have these symptoms
Amenorrhea
Abnormal absence of menstruation
0000141
Asymmetry of the thorax
Asymmetric chest
0001555
Atherosclerosis
Narrowing and hardening of arteries
0002621
Choanal atresia
Blockage of the rear opening of the nasal cavity
Obstruction of the rear opening of the nasal cavity

[ more ]

0000453
Decreased skull ossification
Decreased bone formation of skull
0004331
Dysmenorrhea
Painful menstruation
0100607
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hemangioma
Strawberry mark
0001028
Hypogonadism
Decreased activity of gonads
0000135
Hypopigmented skin patches
Patchy loss of skin color
0001053
Increased intracranial pressure
Rise in pressure inside skull
0002516
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Nephrolithiasis
Kidney stones
0000787
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Oligospermia
Low sperm count
0000798
Optic atrophy
0000648
1%-4% of people have these symptoms
EEG abnormality
0002353
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Motor delay
0001270
Seizure

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    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 GAPO syndrome. Click on the link to view a sample search on this topic.

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