Multiple Capillary Malformations Research Articles

Синдром микроцефалии с капиллярными мальформациями: клинический случай

ABSTRACT INTRODUCTION. Microcephaly-capillary malformation syndrome (MIC-CAP syndrome; OMIM: 614261) is a rare severe autosomal recessive disorder characterized mainly by congenital microcephaly, multiple small capillary malformations of the skin, and drugresistant epilepsy with early onset. The disease results from a mutation in the STAMBP gene. To date, the worldwide prevalence is less than 1:1000000 and less than 30 cases have been described. CASE PRESENTATION. We present a case of MIC-CAP syndrome in a child with a homozygous mutation NC_000002.12: g.73831044A>G (c.188A>G, p.Tyr63Cys) in the STAMBP gene. In the clinical picture: congenital microcephaly, multiple capillary malformations, drug-resistant epilepsy with early onset, gross psycho-motor developmental delay. CONCLUSION. The presented case has all the main characteristic symptoms of the clinical picture of MIC-CAP syndrome. The peculiarity of the case can be considered the presence of renal multicystosis, which has not been previously described in this syndrome. In antiepileptic therapy, the best effect was obtained on duotherapy with valproate and vigabatrin with course addition of clobazam. Given the typical symptom complex of this syndrome, it is advisable to immediately search for a mutation in the STAMBP gene. KEYWORDS: microcephaly, capillary malformations, STAMBP gene, drug-resistant epilepsy

Microcephaly-Capillary Malformation Syndrome

AbstractMicrocephaly-capillary malformation is a relatively new syndrome, which has been reported since 2011 by three different research groups. It is an ultra-rare syndrome characterized by the co-occurrence of microcephaly and multiple capillary malformations in the skin, distal limb anomalies (ranging from nail dystrophy to total absence of one or more phalanxes and mostly localized in the foot), facial dysmorphisms, brain structural anomalies (reduced gyration, widened axial spaces, thin cortex, optic nerve atrophy), early-onset severe intractable epilepsy, and profound mental delay. Autosomal recessive mutations in STAMBP gene (2p13.1) have been reported as the only cause of the disorder, with a high penetrance. Currently, no definitive cure is available for the disorder, and treatment is mainly based on multiple antiepileptic drugs for the treatment of seizures, especially in the first years of life. Data on life-long concerns have not been reported, the older patient described so far being an 8-year-old boy.

5q14.3 Microdeletions: A Contiguous Gene Syndrome with Capillary Malformation–Arteriovenous Malformation Syndrome and Neurologic Findings

Deletions within chromosome region 5q14.3q15 have been associated with a spectrum of disorders including developmental delay, hypotonia, absent speech, mild facial dysmorphism, seizures, and brain anomalies. Some cases of concomitant neurologic abnormalities and cutaneous vascular malformation associated with 5q14.3 deletion have been reported. Previously reported cases had similar features, including multiple capillary malformations, and neurologic abnormalities, including epilepsy, hypotonia, and developmental delay. We report a case of 5q14.3 neurocutaneous syndrome presenting with multiple capillary malformations, neurologic abnormalities, and microdeletion in chromosome 5q14.3.

RASA1 analysis guides management in a family with capillary malformation-arteriovenous malformation.

Capillary malformation-arteriovenous malformation (CM-AVM; MIM 60354) is an autosomal dominant disorder characterized by multifocal cutaneous capillary malformations, often in association with fast-flow vascular lesions, which may be cutaneous, subcutaneous, intramuscular, intraosseus, or cerebral arteriovenous malformations or arteriovenous fistulas. CM-AVM results from heterozygous mutations in the RASA1 gene. Capillary malformations of the skin are common, and clinical examination alone may not be able to definitively diagnose-or exclude- CM-AVM. We report a family in which the proband was initially referred for a genetic evaluation in the neonatal period because of the presence of a cardiac murmur and minor dysmorphic features. Both he and his mother were noted to have multiple capillary malformations on the face, head, and extremities. Echocardiography revealed dilated head and neck vessels and magnetic resonance imaging and angiography of the brain revealed a large infratentorial arteriovenous fistula, for which he has had two embolization procedures. RASA1 sequence analysis revealed a heterozygous mutation, confirming his diagnosis of CM-AVM. We established targeted mutation analysis for the proband's mother and sister, the latter of whom is a healthy 3-year-old whose only cutaneous finding is a facial capillary malformation. This revealed that the proband's mother is also heterozygous for the RASA1 mutation, but his sister is negative. Consequently, his mother will undergo magnetic resonance imaging and angiography screening for intracranial and spinal fast-flow lesions, while his sister will require no imaging or serial evaluations. Targeted mutation analysis has been offered to additional maternal family members. This case illustrates the benefit of molecular testing in diagnosis and making screening recommendations for families with CM-AVM.

A new syndrome with multiple capillary malformations, intractable seizures, and brain and limb anomalies

We present two unrelated male infants with strikingly similar clinical features which have not previously been reported together. The most unusual feature was the presence of multiple small capillary malformations (port-wine stains) on the skin from birth. Both infants had intractable seizures, microcephaly with progressive cortical atrophy, severe developmental delay, dysmorphic facial features, and hypoplasia of the distal phalanges. To our knowledge, no other person with this unique constellation of features has been described.

A locus for hereditary capillary malformations mapped on chromosome 5q.

Capillary malformations (port-wine stains) are the most common vascular malformations occurring in 0.3% of live births. Most capillary malformations occur sporadically and present as a solitary lesion. Capillary malformations can also occur as a component of well-described syndromes. Familial occurrence of multiple capillary malformations has been described in the literature, suggesting autosomal dominant inheritance with variable expression in this subgroup. A hereditary basis underlying the development of solitary capillary malformations has not been found, but may well be possible. We have mapped a locus for an autosomal dominant disorder in a three-generation family that manifested itself with multiple cutaneous capillary malformations to chromosome 5q13-22. This locus spans 48 cM between the markers D5S647 and D5S659 and harbours several candidate genes. By defining the gene(s) responsible for capillary malformations, we will gain more insight in the pathogenesis of this disorder. It is likely that genes implicated in these familial cases may be involved in the more sporadic cases.