Micro syndrome

Overview

Micro syndrome is a rare autosomal recessive genetic disorder characterized by a distinct combination of neurological, ocular, and genital abnormalities. First described in the early 1990s, the name "MICRO" stands as an acronym representing the major features of the syndrome: Mental retardation, Intellectual disability, Congenital cataracts, Retinal dystrophy, and Optic atrophy. Individuals with Micro syndrome typically present in infancy with developmental delays, visual impairments, and later, evidence of brain structure abnormalities on imaging.

Micro syndrome is distinct from but closely related to a group of disorders collectively referred to as Martsolf syndrome. Both conditions share similar features, but Micro syndrome tends to be more severe and is associated with earlier onset of symptoms and more pronounced neurological deficits.

Causes

Micro syndrome is caused by mutations in one of several genes that play a role in intracellular transport and vesicle trafficking. The most commonly implicated genes include:

• RAB3GAP1 – Encodes a protein involved in regulating neurotransmitter release

• RAB3GAP2 – Forms part of the RAB3GAP complex, affecting synaptic vesicle exocytosis

• RAB18 – Plays a role in endoplasmic reticulum structure and lipid droplet dynamics

• TBC1D20 – Involved in GTPase regulation and intracellular trafficking

These mutations are inherited in an autosomal recessive pattern, meaning that both parents must carry one copy of the mutated gene for their child to be affected. Carrier parents are typically asymptomatic. Genetic heterogeneity means that mutations in different genes can result in similar clinical features.

Symptoms

The symptoms of Micro syndrome are typically present from infancy and affect multiple body systems. Common clinical features include:

Neurological Symptoms

• Global developmental delay

• Severe intellectual disability

• Hypotonia (low muscle tone)

• Spasticity, often leading to spastic quadriplegia

• Seizures (in some cases)

• Microcephaly (abnormally small head size)

Ocular Symptoms

• Congenital cataracts (present at birth or developing early in life)

• Microphthalmia (abnormally small eyes)

• Retinal dystrophy (progressive degeneration of the retina)

• Optic atrophy (damage to the optic nerve leading to vision loss)

Genital and Other Physical Anomalies

• Hypogenitalism (underdeveloped genitalia)

• Cryptorchidism (undescended testes in males)

• Delayed puberty or impaired sexual development

Some affected individuals may also exhibit facial dysmorphism, such as a long philtrum, thin upper lip, or a prominent nasal bridge.

Diagnosis

Diagnosis of Micro syndrome involves a combination of clinical evaluation, neuroimaging, ophthalmologic examination, and genetic testing. The diagnostic approach typically includes:

• Clinical assessment: Identification of the triad of intellectual disability, eye anomalies, and genital abnormalities

• Neuroimaging: MRI may reveal corpus callosum hypoplasia, brain atrophy, or other structural abnormalities

• Ophthalmologic exam: Confirms presence of cataracts, retinal dystrophy, and optic nerve issues

• Endocrinologic and urologic evaluations: Assess genital development and hormonal function

• Genetic testing: Confirms mutations in one of the known causative genes (e.g., RAB3GAP1, RAB18)

Carrier testing and prenatal diagnosis may be available for families with a known genetic mutation.

Treatment

There is currently no cure for Micro syndrome. Treatment is supportive and aimed at managing symptoms and improving quality of life. A multidisciplinary team approach is essential and typically includes:

• Neurology: Management of spasticity, seizures, and developmental delays

• Ophthalmology: Cataract removal surgery, visual aids, and management of progressive retinal degeneration

• Endocrinology and urology: Hormonal therapy and surgical correction of genital abnormalities when indicated

• Physical and occupational therapy: To support motor function and daily activities

• Speech and feeding therapy: For children with oral-motor difficulties or feeding issues

• Educational interventions: Special education services tailored to the child’s cognitive abilities

Prognosis

The prognosis for individuals with Micro syndrome is generally guarded due to the severity of developmental, neurological, and visual impairments. Most individuals experience profound intellectual disability and are non-verbal or minimally verbal. Motor disabilities are common and may necessitate wheelchair use or other mobility aids.

Vision often deteriorates progressively due to retinal degeneration and optic atrophy, even after cataract surgery. Life expectancy can vary depending on the severity of complications, such as seizures or feeding difficulties, but many individuals survive into adolescence or adulthood with appropriate supportive care.

Ongoing medical supervision, early intervention, and access to specialized care can significantly improve quality of life and functional abilities for those affected by Micro syndrome.