The current rapid identification and study of new patients with mutations in the PI3K/AKT pathway mean that a definitive reclassification is likely to occur when the full disease spectrum and any genotype-phenotype correlations have been discovered. The management of patients with PROS syndrome includes evaluation after the initial diagnosis, treatment of manifestations, and survivance for potential complications. Nevertheless, failure to detect a PIK3CA mutation does not rule out a clinical diagnosis of PROS in individuals with suggestive features, as this may be due to sub-optimal tissue biopsies or low-level mosaicism. However, MCAP may be diagnosed by testing a blood or saliva sample. The diagnosis of PROS syndrome is based on the clinical features of a patient and is confirmed by a pathogenic variant in one PIK3CA allele in a biopsy sample of the affected tissue. To date, the deformity of overgrowth syndromes caused by somatic PIK3CA mutation includes fibroadipose hyperplasia or overgrowth (FAO), hemihyperplasia multiple lipomatosis (HHML), congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal (CLOVES) syndrome, fibroadipose infiltrating lipomatosis, megalencephaly-capillary malformation (MCAP or M-CM), dysplastic megalencephaly (DMEG), and isolated macrodactyly. ![]() This signaling enzyme is critical for the growth, survival, and metabolism of most cells and is one of the most commonly mutated genes found in cancers. PIK3CA-related overgrowth spectrum (PROS) is an umbrella that covers a wide spectrum of clinical phenotypes, ranging from isolated digit enlargement to extensive overgrowth of the limbs, abdomen, or brain, often in association with vascular malformations. Researchers have identified somatic activating mutations in components of the phosphatidylinositol-3-kinase (PI3K)-PTEN-AKT-mTOR signaling pathway in many patients with different forms of segmental overgrowth. PIK3CA encodes p110α, the catalytic subunit of phosphatidylinositide-3-kinase (PI3K). Affected patients commonly develop distorting or restricting overgrowth, leading to marked functional impairments. Segmental overgrowth is excessive growth affecting only some parts of the body. It is almost invariably asymmetrical and a feature of a heterogeneous group of rare disorders, which often carry a significant burden of morbidity and mortality. Further studies and investigations on PROS syndrome are needed to aid in making a definitive classification and treatment of such complex and rare diseases. To the best of our knowledge, this is one of the first cases of PROS in Saudi Arabia, which illustrates the classical findings of MCAP syndrome. The patient is on overgrowth protocol for PIK3CA, which includes alpha-fetoprotein and abdominal ultrasound every three months until the age of eight years. Finally, the diagnosis was confirmed by WES, which detected changes in the PIK3CA gene. MRI studies showed megalocephaly, bilateral perisylvian polymicrogyria, bilateral peri-regional, high T2 signal intensities, and cerebellar tonsil ectopia with crowding of the posterior fossa. The facial features include low-set ears, frontal bossing, depressed nasal bridge, and bilateral esotropia. Clinically, the patient had speech and developmental delay, macrocephaly, joint hyperlaxity, unsteady gait, and subtle dysmorphic facial features. The diagnosis was based on clinical presentation, imaging studies, and whole-exome sequencing (WES). Our patient was a 46-month-old boy, who is diagnosed with MCAP syndrome. Therefore, reporting such cases will help us understand them and thus develop an appropriate treatment for them. ![]() To date, there is no curative treatment for patients with MCAP syndrome. The management of patients with MCAP syndrome includes evaluation after the initial diagnosis, treatment of manifestations, and surveillance for potential complications. The diagnosis of PROS syndrome is based on the clinical features of a patient and confirmed by a pathogenic variant in one PIK3CA allele in a biopsy of the affected tissue. One of these disorders is megalencephaly capillary malformation polymicrogyria syndrome (MCAP), which is characterized by cutaneous capillary malformations, megalencephaly, cortical brain malformations, abnormalities of somatic growth with body and brain asymmetry, developmental delay, and characteristic facial dysmorphism. PIK3CA-related overgrowth spectrum (PROS) is an umbrella that includes a broad range of rare disorders, ranging from isolated digit enlargement to extensive overgrowth of the limbs, abdomen, or brain.
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