Sturge-Weber syndrome: Difference between revisions
| Line 169: | Line 169: | ||
* Beckwith-Wiedemann syndrome | * Beckwith-Wiedemann syndrome | ||
|PHACE syndrome | |PHACE syndrome | ||
[P: Posterior fossa brain malformation | [P: Posterior fossa brain malformation | ||
| Line 180: | Line 179: | ||
E: Endocrine and eye abnoramlities] | E: Endocrine and eye abnoramlities] | ||
==Treatment== | ==Treatment== | ||
Revision as of 23:27, 12 June 2020
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2] Rina Ghorpade, M.B.B.S[3]
Synonyms and keywords: Encephalotrigeminal angiomatosis.
Overview
Sturge-Weber syndrome(SWS), sometimes referred to as encephalotrigeminal angiomatosis, is an extremely rare congenital neurological and skin disorder. It is one of the phakomatoses, and is often associated with port-wine stains of the face, which is a capillary malformation, glaucoma, seizures, mental retardation, and ipsilateral leptomeningeal angioma. It is caused by an arteriovenous malformation that occurs in the cerebrum of the brain on the same side as the physical signs described above. Normally, only one side of the head is affected. It is an embryonal developmental anomaly resulting from errors in mesodermal and ectodermal development. Unlike other neurocutaneous disorders (phakomatoses), Sturge-Weber does not have a hereditary tendency but occurs sporadically. The diagnosis of SWS is established with neuroimaging techniques such as MRI with contrast, which shows the presence of leptomeningeal malformations in the brain. Treatment of this is symptomatic such as seizures are treated with anti-epileptic medications, ocular symptoms are managed with surgical modalities, and skin manifestations are treated with the laser. Prognosis of SWS is dependent on the age of onset of seizures, the extent of the brain, and dermatological involvement.
Historical Perspective
The term Sturge-Weber syndrome was coined by Professor Hilding Bergstrand in 1935 to acknowledge the work of two physicians, William Allen Sturge, and Parkes Weber. [1] In 1879 William Allen Sturge noted a case of right sided facial lesion, ocular abnormalities, and neurological involvement in a six and half year old female. He later named this facial lesion as a port wine stain. In 1922, Parkes Weber, described the radiogical features of a brain lesion in a twenty-two year old woman with left sided vascular lesion on of her trunk, with right sided congenital spastic hemiplegia.[2]
Classification
Encephalotrigeminal angiomatosis may be classified according to facial and leptomeningeal involvement into three subtypes by using Roach Scale.
Type I: Classic Sturge-Weber syndrome that involves both facial, and leptomeningeal involvement, may have glaucoma.
Type II: Only facial angiomatosis with no CNS involvement, may have glaucoma.
Type III: Only CNS involvement, and no glaucoma.
Pathophysiology and Genetics
The cause of SWS is somatic mosaic mutations in the GNAQ gene. The GNAQ gene is located on the long arm of chromosome number 9, at the position 21.2, and comprise of 7 exons. The function of this gene is to produce a protein called guanine nucleotide-binding protein G-alpha-q, which functions to regulate intracellular signaling pathways to help regulate the structure and functions of blood vessels. The somatic mutation in this gene (mutation that is occurring after conception and which is not inherited) replaces the amino acid arginine with the amino acid glutamine at position 183 in the G-alfa-q protein. This mutation specifically affects the cell responsible for angiogenesis in brain, skin and eyes. Other somatic mutation in GNAQ gene is responsible for the development of uveal melanoma, however, patients with SWS are not at high risk for the development of uveal melanoma.
On gross pathological examination, the leptomeninges looks thickened and the leptomeningeal vessels show dilatations and tortuosities. These vessels in leptomeninges show overexpression of Fibronectin and Vascular Endothelial Growth Factors (VEGF).[3]
On microscopic histopathological analysis of brain tissues show, intracranial calcification, gliosis, hypoplastic blood vessels, and loss of neurons. It is hypothesized that the hypoxic injury to the endothelial cells can lead to the breakdown of blood-brain barrier and can cause intracranial calcification. [4]
Clinical Features
Neurological manifestations
SWS is characterized by the formation of leptomeningeal capillary-venous malformation or angioma, which can cause various neurological symptoms such as seizures, stroke, intellectual disabilities, and behavioral issues. Intracranial angiomas occur on the same facial port-wine stain, it usually involves occipital and parietal lobes.[1]
- Seizures
Seizures is the most common symptom of SWS seen in 75-90% of patients , and it is often the first presentation. The age of onset of seizures is usually in early childhood, but it can occur at any age. The risk of seizures is high with a bilateral port-wine stain that unilateral port-wine stain.[5] At first, seizures are focal, but later in the course can turn into generalized tonic-clonic seizures. Rarely, a small subgroup of patients can present with infantile spasm and atonic seizures.
- Stroke like episodes
Possibly chronic hypoxia-induced injury in leptomeningeal blood vessels leads to stroke-like events. They occur in 25-60% of patients with SWS. These stroke-like episodes occur concurrently with the seizures and can lead to hemiparesis. Hemiparesis usually occur contralateral to the brain lesions. Children are more prone to develop these stroke-like episodes due to repeated falls and minor head injuries.[6].
- Cognitive impairment
Cognitive impairment in the form of delayed neuropsychological development occur in 50-60% patients with SWS, and it may range from mild attention deficit to severe deterioration in the mental capacity. Early-onset of seizures is associated with the high risk of developing severe forms of cognitive impairment.[5]. Other behavioral problems associated with SWS are Autism Spectrum Disorder, social communication difficulties. [7]. Adults with normal cognitive function usually have depression, while aggression and self-destructive behavior occur in intellectually impaired adults.[4]
- Migraine like headaches
Headaches are very common symptoms of SWS Kossoff et al. reported the headaches can be as debilitating as seizures, the median age of onset of headache is 8. They also reported that the patients with a family history of headaches have an earlier age at onset of headache. [8]
- Neuroendocrine problems
A retrospective study conducted by Miller et al. concluded that the prevalence of the growth hormone deficiency is 18 fold higher than that of the general population.[9] The etiology of growth hormone deficiency in SWS is not well understood, interestingly, there is radiological undetectable structural damage to the pituitary gland. There is a higher incidence of central hypothyroidism in patients with SWS, due to an aberration in hypothalamic-pituitary axis resulting from neuronal abnormalities. [10] Therefore, patients with SWS should undergo screening tests such as thyroid function tests for central hypothyroidism and insulin-like growth factor-1 levels (IGF-1) to detect growth hormone deficiency.
Opthalmological issues
- Glaucoma
It is the most common ocular manifestation of SWS, and glaucoma occurs in nearly 70% of patients with SWS.[11] Usually glaucoma occurs ispilateral to the port-wine stain. The mechanism of pathogenesis of glaucoma are abnormality of an angle of anterior chamber which increases the resistance to the flow of aqueous humor, and higher venous pressure in episcleral veins due to formation of atriovenous malformations especially in patients with episcleral hemangioma.[12]
Nearly 50% of patients with SWS present with buphthalmos (enlargement of an eye globe in newborns), and the risk of afflicted glaucoma is the highest in the first decade of life.
- Other Ocular Manifestations
Choroidal hemangioma present in nearly 50% of patients with SWS. Other opthalmological problems in patients with SWS are retinal detachment, heterochromia iridium, and strabismus.
Port Wine Stain (PWS)
Port-wine stains are capillary malformations and are the most common skin manifestation of SWS. They are present at birth, usually occur on one side of the face, although these lesions can occur bilaterally. At birth, these stains are pink in color, however, the appearance of these stains changes with time, they grow dark red with increasing age. These lesions appear nodular and thick due to the dilatation of superficial vessels. PWS follows the distribution of three sensory divisions of trigeminal nerve, V1 the frontal branch, V2 the maxillary branch, and V3 the mandibular branch. In SWS the port-wine stains usually occur on the forehead, upper eyelid.
Port-wine stains are often misdiagnosed as a salmon patch or Nevus simplex or infantile hemangioma.
The following table distinguishes the common differential diagnosis of the port-wine stains.
| Features | Port-wine stain | Salmon patch | Infantile hemangioma |
|---|---|---|---|
| Other names |
|
|
|
| Pathology |
|
|
|
| Color |
|
|
|
| Distribution |
|
|
|
| Age at presentation |
|
|
|
| Progression |
|
|
|
| Association |
|
|
PHACE syndrome
[P: Posterior fossa brain malformation H: Hemangiomas A: Arterial abnormalities C: Cardiac anomalies, coarctation of the aorta E: Endocrine and eye abnoramlities] TreatmentTreatment for Sturge-Weber syndrome is symptomatic. Laser treatment may be used to lighten or remove the birthmark. Anticonvulsant medications may be used to control seizures. Doctors recommend yearly monitoring for glaucoma, and surgery may be performed on more serious cases. Physical therapy should be considered for infants and children with muscle weakness. Educational therapy is often prescribed for those with mental retardation or developmental delays, but there is no complete treatment for the delays. Brain surgery involving removing the portion of the brain that is affected by the disorder can be successful in controlling the seizures experienced so that the patient has only a few seizures that much less intnse than pre-surgery. One of the hospitals that has successfully completed this procedure is Shands at the University of Florida. PrognosisAlthough it is possible for the birthmark and atrophy in the cerebral cortex to be present without symptoms, most infants will develop convulsive seizures during their first year of life. There is a greater likelihood of intellectual impairment when seizures start before the age of 2 and are resistant to treatment. EponymIt is named for William Sturge and Frederick Parkes Weber.[13][14][15] References
PicturesTemplate:Phakomatoses and other congenital malformations not elsewhere classified |