Bonnemann-Meinecke-Reich syndrome (BMRS), also known as encephalopathy intracranial calcification growth hormone deficiency microcephaly retinal degeneration, is a rare congenital disease that is characterized by brain, eye and growth abnormalities. Its pattern of inheritance may be autosomal recessive. The symptoms, such as developmental delay, usually appear within the first year of life. There are very few known cases of BMRS, reported in only two families to date. These cases were recorded in 1989 and 1991.
Bonnemann-Meinecke-Reich syndrome (BMRS) is a congenital illness that is inherited and thought to follow an autosomal recessive pattern. It is extremely rare and has only been reported in a few families, affecting siblings . The pathological process, as well as the appearance of symptoms, begin within the first year of life. BMRS represents a group of congenital encephalopathies that are characterized by calcifications within the brain. They originate from diverse genetic mutations .
The main features of BMRS that give rise to the clinical presentation are encephalopathy due to calcification of parts of the brain, typically the basal ganglia and cerebrum, as well as ventricular dilation . Overall, presentation between patients varies. Individuals showcase a delay in psychomotor ability, below average intellectual capability, and mental retardation. Other manifestations are ataxia and muscle spasticity. Affected children also exhibit various dysmorphic features such as microcephaly, as well as craniosynostosis, which is the premature fusion of sutures leading to abnormal skull shape . Furthermore, they have difficulties with vision because of retinal degeneration.
Due to the deficiency in growth hormone, dwarfism or short stature are often observed. In addition, there may be hypoplasia of certain organs, namely the adrenal glands and uterus, as well as dysfunction of endocrine glands, including the pituitary and thyroid glands, leading to hormonal derangements .
History taking and physical examination are initially conducted. Subsequently, numerous laboratory and imaging studies can be carried out as dictated by the patient's presenting symptoms. Laboratory tests may include:
- The measurement of growth hormone (GH) levels.
- Evaluation of the functioning of the thyroid, parathyroid, and adrenal glands.
- Metabolic panel, with measurement of ion levels of calcium and phosphorus.
- TORCH (toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus, and herpes infections) screen.
- Cerebrospinal fluid (CSF) analysis, which may be normal.
Imaging studies :
- Electroencephalography (EEG): individuals with Bonnemann-Meinecke-Reich syndrome may exhibit abnormal wave patterns .
- Skull X-ray: may show calcifications.
- Computerized tomography (CT) scanning: calcifications and dilated ventricles may be seen.
- Magnetic resonance imaging (MRI): this may reveal calcifications and brain atrophy in regions exemplified by the brainstem and cerebellum, as well as features suggestive of leukodystrophy.
- Fundoscopy: this may reveal retinal pigmentation.
- Billard C, Dulac O, Bouloche J, et al. Encephalopathy with calcifications of the basal ganglia in children: a reappraisal of Fahr's syndrome with respect to 14 new cases. Neuropediatrics. 1989;20(1):12-19.
- Kendall B, Cavanagh N. Intracranial calcification in paediatric computed tomography. Neuroradiology. 1986;28(4):324-30.
- Bönnemann CG, Meinecke P, Reich H. Encephalopathy with intracerebral calcification, white matter lesions, growth hormone deficiency, microcephaly, and retinal degeneration: two sibs confirming a probably distinct entity. J Med Genet. 1991;28(10):708–711.
- National Institutes of Health. Encephalopathy intracranial calcification growth hormone deficiency microcephaly retinal degeneration. Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/2113/encephalopathy-intracranial-calcification-growth-hormone-deficiency-microcephaly-retinal-degeneration. Accessed March 14, 2018.
- Orphanet. Bonnemann-Meinecke-Reich syndrome. Orphanet. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1261. Accessed March 14, 2018.
- Online Mendelian Inheritance in Man. Encephalopathy with intracranial calcification, growth hormone deficiency, microcephaly, and retinal degeneration. Online Mendelian Inheritance in Man. https://www.omim.org/entry/225755. Updated March 5, 2002. Accessed March 14, 2018.