Micro Syndrome; WARBM; Warburg-Sjo-Fledelius Syndrome

Warburg micro syndrome (WARBM) is an extremely rare genetic disorder that primarily affects the development of the eyes, brain, and endocrine system. It is characterized by severe intellectual disability and progressive neurological decline beginning in infancy. WARBM is caused by mutations in the RAB3GAP1, RAB3GAP2, RAB18, or TBC1D20 genes.

Diagnostic testing: The diagnosis of WARBM is made by:

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  Clinical evaluation/examination;

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  Molecular genetic testing to identify mutations in the RAB3GAP1, RAB3GAP2, RAB18, or TBC1D20 genes; and

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  Brain magnetic resonance imaging (MRI).

Physical findings:

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  Congenital cataracts;

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  Microphthalmia (one or both eyes abnormally small);

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  Small pupils;

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  Optic atrophy;

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  Developmental delay;

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  Progressive spastic diplegia;

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  Seizures;

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  Brain abnormalities such as corpus callosum hypoplasia, polymicrogyria, and cortical atrophy;

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  Microcephaly (small head circumference);

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  Cryptorchidism/micropenis in males and hypoplastic genitalia in females; and

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  Facial features with wide nasal bridge, deep set eyes, and narrow mouth.

ICD-9: 759.89

ICD-10: Q87.0; Q87.89

Signs and symptoms of WARBM are present in early infancy, with progressive neurological decline. Individuals with WARBM have severe intellectual disability and other neurological features due to problems with growth and development of the brain. Affected individuals have delayed development and may never be able to sit, stand, walk, or speak. They usually have weak muscle tone (hypotonia) in infancy. By early childhood, they develop muscle stiffness (spasticity) and joint deformities (contractures) that restrict movement in the legs. The muscle problems worsen (progress) to include the arms and lead to paralysis of all four limbs (spastic quadriplegia). Eventually, breathing may be impaired. Brain abnormalities can contribute to vision problems (cortical visual impairment). Individuals with WARBM may also have recurrent seizures (epilepsy).

There is no cure for WARBM . Management is symptom specific and supportive. Antiepileptic medication is used for seizures; physical therapy/occupational therapy is used to address spasticity, contractures and severe developmental delay; surgery is used to remove congenital cataracts, and hormone treatments are used to address hypogonadism (small/undescended testes or delayed puberty).

Suggested MER for Evaluation:

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  Clinical history and examination that describes the diagnostic features of the impairment;

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  Genetic sequencing tests confirming mutation of the RAB3GAP1, RAB3GAP2, RAB18, or TBC1D20 genes;

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  Ophthalmologic evaluation reports of visual acuity; and

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  Results of MRI of the brain.

1.18

2.02

11.02

11.07

12.02

12.05

101.18

101.24

102.02

110.08

111.02

111.07

112.02

112.05

112.14

11.07

111.07