Diseases identified by IAROD
National Rare Diseases Data Bank (BNDMR): updated December 3, 2024
- Neurofibromatosis type 1 (Code 636)
A clinically heterogeneous neurocutaneous genetic disorder characterized by café-au-lait spots, Lisch nodules in the iris, axillary and inguinal freckles, and multiple neurofibromas.
Number of cases in the BNDMR: 13,411
- Congenital glaucoma (code 98976)
A rare eye disease characterized by high intraocular pressure. Clinically, there is an increase in eye volume often associated with corneal edema.
Number of cases in the BNDMR: 640
- Glioma of the optic pathway (code 2086)
Optic pathway glioma is a benign tumor that develops along the optic nerve (chiasm, tract, and radiations). It is characterized by impaired or lost vision and may be accompanied by diencephalic manifestations, such as reduced growth and altered sleep patterns. Optic pathway glioma is often associated with neurofibromatosis type 1 (NF1).
Number of cases in the BNDMR: 318
- Isolated congenital ectropion (code 99171)
A rare eye disease characterized by congenital malposition of the lower or upper eyelids, unilateral or bilateral, with eversion of the edge due to vertical shortening of the skin tissue, resulting in exposure of the conjunctiva and sometimes the cornea. In severe cases, chronic epiphora and exposure keratitis may be observed.
Number of cases in the BNDMR: <10
- Juvenile glaucoma (code 98977)
A rare form of early-onset glaucoma characterized by a significant increase in intraocular pressure that appears early and progresses rapidly, leading to optic nerve excavation and substantial visual impairment if left untreated.
Summary
Epidemiology
According to estimates, the disease affects 0.32/100,000 people before the age of 20.
Clinical description
Juvenile glaucoma (JG) usually manifests between the ages of 5 and 18, but it can appear later. Patients are initially asymptomatic, and the disease is often discovered incidentally during a routine examination. JG is usually bilateral, and marked asymmetry between the two eyes may be observed. Intraocular pressure increases gradually, leading to optic nerve excavation and, eventually, substantial visual impairment and loss of visual field.
Etiology
GJ is caused by impaired aqueous humor flow through the trabecular meshwork and into Schlemm’s canal. Mutations in the MYOC gene (1q23-q24) have been identified in affected patients. The MYOC gene encodes myocilin, a glycoprotein found in the trabecular meshwork and ocular tissues.
Diagnostic method(s)
GJ is caused by impaired flow of aqueous humor through the trabecular meshwork and into Schlemm’s canal. Mutations in the MYOC gene (1q23-q24) have been identified in affected patients. The MYOC gene encodes myocilin, a glycoprotein found in the trabecular meshwork and ocular tissues.
Differential diagnosis
The differential diagnosis includes other forms of open-angle glaucoma that can occur at any age, late-onset congenital glaucoma, steroid-induced glaucoma, traumatic glaucoma, and inflammatory glaucoma.
Genetic counseling
The mode of transmission is autosomal dominant with high penetrance. Genetic testing can be performed to identify family members at risk of developing GJ. Genetic counseling should be offered to individuals who carry the mutation responsible for the disease to inform them that there is a 50% risk of passing the mutation on to their offspring.
Management and treatment
Medical treatment (carbonic anhydrase inhibitors, beta-blockers, prostaglandin analogues) is often useful in treating GJ. When the disease does not respond to treatment, angle surgery (goniotomy, trabeculotomy), filtration surgery (trabeculectomy), laser treatment (laser angle surgery or cyclodiode laser therapy) and/or aqueous humor drainage devices may be considered.
Progn
The prognosis is favorable in patients diagnosed and treated early. Without treatment, progression to blindness is possible.
https://www.orpha.net/fr/disease/detail/98977
Number of cases in the BNDMR: 80
- Microphthalmia-cataract syndrome (code 2543)
Isolated microphtalmia-anophthalmia-coloboma (2542)
Definition
A non-syndromic group of structural developmental abnormalities of the eye characterized by an inconsistent combination of microphtalmia, ocular coloboma, and anophthalmia, unilateral or bilateral, in the absence of any association with other ocular abnormalities of the affected/contralateral eye, and in the absence of systemic abnormalities.
Summary
Epidemiology
The prevalence of microphthalmia is 1 in 7,000, that of anophthalmia is 1 in 30,000, and that of coloboma is 1 in 5,000 live births, with a combined prevalence of 3 to 30 per 100,000 births.
Associated malformations affect 32 to 93% of patients. No clear predilection for any ethnic group or gender has been found.
Clinical description
Microphtalmia-anophthalmia-coloboma (MAC) is a phenotypic continuum of congenital eye malformations that are apparent at birth.
Sometimes, as in the case of retinal coloboma or mild microphthalmia, the abnormality may be detected later in life. True anophthalmia is a failure of eye development at the optic vesicle stage (between 3 and 4 weeks of gestation), resulting in the absence of the eye, optic nerve, and chiasm. Clinical anophthalmia (also known as severe microphthalmia) is often observed, with a small cystic remnant detected on pathological examination/imaging.
Nanophtalmia and posterior microphthalmia are rare subtypes of microphthalmia, characterized by a structurally normal eye but with a reduced axial length (<20 mm) and severe hyperopia. Ocular coloboma may affect the inferonasal aspect of the eye, including the iris, ciliary body, zonules, retina, retinal pigment epithelium (RPE), choroid, and/or optic disc.
Etiology
The etiology of MAC is complex and the causes are both monogenic, chromosomal, and environmental. Mutations in SOX2, OTX2, and STRA6 are responsible for 75% of cases of bilateral anophthalmia and severe microphthalmia. Chromosomal abnormalities account for 20-30% of MAC. Environmental factors associated with anophthalmia include maternal infections, smoking, and prenatal exposure to certain drugs.
Maternal vitamin A deficiency, alcohol abuse, and the use of teratogenic drugs during pregnancy have been associated with coloboma and microphthalmia.
Diagnostic method(s)
Postnatal diagnosis may be based on clinical examination, with actual/clinical anophthalmia confirmed by MRI of the brain and orbit. Molecular diagnosis can be established through genetic testing, using comparative genomic hybridization (aCGH) or whole exome/genome sequencing.
Differential diagnosis
Differential diagnoses aim to rule out aniridia, anterior segment dysgenesis, congenital corneal opacity, sclerocornia, cryptophtalmia, cyclopia, and congenital cystic eye. MAC can also occur in association with various syndromes, so it is recommended that specialists be consulted to investigate for systemic diseases (e.g., concomitant neurological or pituitary deficits). Genetic diagnosis may be useful to identify possible systemic abnormalities.
Prenatal diagnosis
Prenatal diagnosis of anophthalmia or microphthalmia can be established by 2D or 3D ultrasound during the second trimester (or at 12 weeks of pregnancy by transvaginal ultrasound) or fetal MRI to visualize the orbit.
Genetic counseling
Genetic counseling may be difficult due to the large number of known genetic causes and phenotypic variability. The mode of transmission is difficult to predict due to de novo mutations, mosaicism, and non-penetrance. If a genetic diagnosis is established, informed family planning advice can be provided, including prenatal and preimplantation diagnosis.
Management and treatment
There is no treatment for patients with MAC. They should be managed by a multidisciplinary team of specialists, including ophthalmologists, pediatricians, and clinical geneticists. If there is visual potential, children should be monitored to optimize their vision and correct refractive errors or strabismus and prevent amblyopia. Fundus examination should be performed in patients with chorioretinal coloboma, which is associated with a risk of retinal detachment. Visual aids should be used to compensate for visual impairment. In cases of severe microphthalmia or anophthalmia, the orbit can be enlarged using cosmetic shells/conformers to minimize facial deformity.
Prognosis
Isolated MACs are congenital structural malformations for which there is no treatment.
https://www.orpha.net/fr/disease/detail/2542
Number of cases in the BNDMR: 20
- Secondary glaucoma (code 238763)
Glaucoma secondary to spherophakia/lens ectopia and megalocornia
Definition
A rare, non-syndromic genetic eye development anomaly characterized by congenital megalocornia associated with spherophakia and/or lens ectopia, resulting in pupillary block and secondary glaucoma. Other features may include a plateau iris, iridodonesis, axial myopia, very deep anterior chambers, miotic and oval pupils without well-defined edges, eye pain and irritation manifested by conjunctival injection, corneal edema and central scarring, and an ogival palate.
https://www.orpha.net/fr/disease/detail/238763
Number of cases in the BNDMR: 13
- Primary early-onset glaucoma (code 156005)
Group of pathologies
- Congenital glaucoma ORPHA:98976
- Juvenile glaucoma ORPHA:98977
Congenital glaucoma
Definition
A rare ophthalmic disease characterized by high intraocular pressure. Clinically, there is an increase in eye volume often associated with corneal edema. Summary
Epidemiology
Epidemiology
Congenital glaucoma (CG) is the most common type of glaucoma in early childhood. The prevalence at birth is estimated at approximately 1 in 45,450 live births in Europe.
Boys are more commonly affected than girls, and the disease is bilateral in 70 to 80% of cases.
Clinical
The diagnosis is made during the first year of life in nearly 80% of cases. It is defined by the classic triad of epiphora, blepharospasm, and photophobia.
Affected children have watery and red eyes, corneal opacity, and increased eye volume resulting from stretching of the immature eye due to increased intraocular pressure.
Children over the age of 3 experience progressive myopia and insidious visual field loss.
Etiology
The etiology remains poorly understood, but the disease is thought to be caused by obstruction of the flow of aqueous humor in the iridocorneal angle at the level of the trabecular meshwork.
Genetic mapping of affected families has identified three chromosomal loci, GLC3A at 2p22.2, GLC3B at 1p36, and GLC3C at 14q24.3-q31.1, with mutations in the CYP1B1 gene (at 2p22.2) located at GLC3A. Mutations in the LTBP2 (in 14q24.3) and MYOC (in 1q23-q24) genes have also been identified.
Diagnostic method(s)
The diagnosis is based on a comprehensive ophthalmological examination revealing an opaque cornea with increased diameter and Haab’s streaks, elevated intraocular pressure (IOP) (a pressure greater than 20 mmHg or an asymmetry of more than 5 mmHg is a warning sign), a deep anterior chamber, anteriorly inserted iris, incomplete development of the scleral spur (analysable by gonioscopy), a high ratio between the diameter of the excavation (C for cup) and the diameter of the papilla (D for disc) of the optic nerve head, and myopia and astigmatism revealed by a refraction test.
An examination under anesthesia may be performed if necessary.
Differential diagnosis
The differential diagnosis for redness and watery eyes is obstruction of the lacrimal duct, conjunctivitis, corneal abrasion, and uveitis, and for enlarged cornea, high axial myopia and megalocornia.
The differential diagnosis of corneal opacity and edema aims to rule out congenital corneal dystrophies, trauma during birth, keratitis, congenital eye abnormalities, or storage diseases, while that of papillary excavation aims to rule out physiological excavation, papillary coloboma, genetic optic atrophy, and optic nerve hypoplasia.
Prenatal diagnosis
Prenatal diagnosis can determine the risk of the disease when the mutation is known in the family.
Genetic counseling
Most cases are sporadic, with approximately 10% of cases showing autosomal recessive transmission and variable penetrance.
In the case of autosomal recessive transmission, genetic counseling should be offered to at-risk couples (both parents are carriers of a causal mutation) to inform them that there is a 25% risk of having an affected child in each pregnancy.
Management and treatment
Congenital glaucoma is mainly treated surgically, with medication playing only a supporting role.
Initially, angle surgery (such as goniotomy or trabeculotomy), trabeculectomy, or deep sclerectomy is usually performed. The choice depends on the severity of the glaucoma and the surgeon’s preferences.
Glaucoma drainage devices and diode laser cyclophotocoagulation are used in refractory cases. Amblyopia, corneal scarring, and cataracts are late complications. Early visual rehabilitation is important to prevent amblyopia. Patients may require regular follow-up throughout their lives to monitor IOP.
Prognosis
The prognosis is closely related to the time of onset of the disease; early diagnosis and prompt surgical treatment contribute significantly to visual improvement. Pressure is well controlled in most patients treated successfully in early childhood who maintain stable optic nerves and a fully functional visual field into adulthood.
https://www.orpha.net/fr/disease/detail/98976
Number of cases in the BNDMR: <10
- Neovascular glaucoma (code 94058)
Neovascular glaucoma is the most common type of secondary glaucoma. It is usually caused by diabetic retinopathy, central retinal vein occlusion, and carotid artery obstruction, but can sometimes result from trauma, uveitis, or eye tumors.
It is characterized by severe eye pain, angle-closure glaucoma, high intraocular pressure, and can lead to vision loss.
https://www.orpha.net/fr/disease/detail/94058
Number of cases in the BNDMR: <10
- Congenital ectropion of the pigmented epithelium of the IRIS (code 91491)
Congenital ectropion of the pigmented epithelium of the iris is a rare, genetic, non-syndromic eye development disorder characterized by the presence of the pigmented epithelium of the iris on the anterior surface of the iris, anterior insertion of the iris, angular dysgenesis, and progressive open-angle glaucoma (the latter may occur during early childhood or develop later in life).
Patients may experience headaches, eye pain, photophobia, and redness, tearing, and/or swelling of the eye. It may sometimes be associated with neurofibromatosis and, more rarely, with other eye abnormalities.
https://www.orpha.net/fr/disease/detail/91491
Number of cases in the BNDMR: <10
- Various types of damage to the optic nerve
ORPHA:637064 (Pathology) Isolated optic nerve aplasia
ORPHA:637061 (Pathology) Isolated optic nerve hypoplasia
ORPHA:137905 (Group of disorders) Syndromic optic nerve hypoplasia
ORPHA:519337 (Group of disorders) Disease with optic nerve compression
ORPHA:522512 (Group of disorders) Rare genetic disorder of the optic nerve
ORPHA:519351 (Group of disorders) Rare disorder of the optic nerve
ORPHA:250972 (Pathology) Polymicrogyria with optic nerve hypoplasia
ORPHA:397618 (Pathology) Foveolar hypoplasia-optic nerve decussation defect-anterior segment dysgenesis syndrome
ORPHA:313800 (Pathology) Retinal dystrophy syndrome-optic nerve edema-splenomegaly-anhidrosis-migraine headache
ORPHA:1475 (Pathology) Kidney-coloboma syndrome
Number of cases in the BNDMR: <10