Macrocephaly–capillary malformation: Analysis of 13 patients and review of the diagnostic criteria

Martínez‐Glez, Víctor; Romanelli, Valeria; Mori, María Ángeles; Gracía, Ricardo; Segovia, Mabel; González‐Meneses, Antonio; López‐Gutiérrez, Juan Carlos; Geán, Esther; Martorell, Loreto; Lapunzina, Pablo

doi:10.1002/ajmg.a.33514

Cited by 60 publications

(64 citation statements)

References 26 publications

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“…More than 140 cases have been reported in the literature and numerous sets of diagnostic criteria proposed [Clayton-Smith et al, 1997;Moore et al, 1997;Franceschini et al, 2000;Lapunzina et al, 2004;Conway et al, 2007;Gonzalez et al, 2009;Martínez-Glez et al, 2010]. The most consistent features of MCAP appear to be congenital or early postnatal MEG and cutaneous capillary malformations, such as persistent nevus flammeus and/or vivid cutis marmorata .…”

Section: Mcap: a Disorder Of Brain And Body Overgrowthmentioning

confidence: 99%

Megalencephaly Syndromes and Activating Mutations in the PI3K‐AKT Pathway: MPPH and MCAP

Mirzaa¹,

Rivière²,

Dobyns³

2013

American J of Med Genetics Pt C

147

138

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The megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) and megalencephaly-capillary malformation (MCAP) syndromes are highly recognizable and partly overlapping disorders of brain overgrowth (megalencephaly). Both syndromes are characterized by congenital or early postnatal megalencephaly, with a high risk for progressive ventriculomegaly leading to hydrocephalus and cerebellar tonsillar ectopia leading to Chiari malformation, and cortical brain abnormalities, specifically polymicrogyria. MCAP is further characterized by distinct cutaneous capillary malformations, finger or toe syndactyly, postaxial polydactyly, variable connective tissue dysplasia and mild focal or segmental body overgrowth, among other features. MPPH, on the other hand, lacks consistent vascular or somatic manifestations besides postaxial polydactyly in almost half of reported individuals. We identified de novo germline mutations in PIK3R2 and AKT3 in individuals with MPPH, and both postzygotic, mosaic and rare germline mutations in PIK3CA in individuals with MCAP. PIK3R2, AKT3, and PIK3CA are members of the critical phosphatidylinositol-3-kinase (PI3K)-vakt murine thymoma viral oncogene homolog (AKT) pathway that is well implicated in cell growth, proliferation, survival, apoptosis, among other diverse cellular functions. The identified mutations in these three genes have been shown to lead to gain of function and activation of the PI3K-AKT pathway. Germline and postzygotic mutations of PIK3CA and other PI3K-AKT-mTOR pathway genes have also been identified in several other overgrowth syndromes, highlighting the key role of this signaling pathway in normal development and pathophysiology of a large group of congenital anomalies.

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Section: Mcap: a Disorder Of Brain And Body Overgrowthmentioning

confidence: 99%

Megalencephaly Syndromes and Activating Mutations in the PI3K‐AKT Pathway: MPPH and MCAP

Mirzaa¹,

Rivière²,

Dobyns³

2013

American J of Med Genetics Pt C

147

138

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“…It is presumed to be genetic in origin; however, no common genetic defect has yet been found, 9 although a subset of these patients may have PIK3CA mutations. 11 It appears likely that many of these patients are genetic mosaics, with abnormalities manifesting in the tissues that carry a mutation.…”

Section: Discussionmentioning

confidence: 99%

“…There are several characteristic imaging findings in MCAP, including ventriculomegaly, cavum septum pellucidum, cerebellar tonsillar herniation, and cerebral and/ or cerebellar asymmetry. 9 Several diagnostic criteria schemata have been proposed 3,4,6,9,12,15 based on anatomical and radiographic findings, but there is no clear diagnostic consensus yet. Diagnosis is made based on clinical criteria alone.…”

Section: Discussionmentioning

confidence: 99%

Severe holocord syrinx in a child with megalencephaly-capillary malformation syndrome

Segal¹,

Heary

Sabharwal

et al. 2016

PED

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The authors present the case of a child with megalencephaly-capillary malformation syndrome who developed a rapidly progressive holocord syringomyelia that was treated surgically. A 3-year-old boy with megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome presented with several months of right leg weakness, worsening scoliosis, and increased seizures. An MRI study of the brain demonstrated a Chiari I malformation and massively dilated syringomyelia extending from C-2 to the conus medullaris. The patient underwent an urgent suboccipital craniectomy with C1–3 laminectomies to relieve the CSF outflow obstruction with significant clinical improvement. Surgery was complicated by bleeding from intracranial vascular malformations. This report describes a very rapidly developing, massive holocord syringomyelia related to CSF obstruction due to an unusual congenital brain malformation and associated vascular overgrowth at the site. Serial, premorbid MRI studies demonstrated the very rapid progression from no Chiari malformation, to progressively greater cerebellar tonsillar herniation, to holocord syrinx. This complication has never been reported in MCAP syndrome and should be considered in any affected MCAP patient with a progressive neurological decline, even if previous spine imaging findings were normal. Surgical complications due to hemorrhage also need to be considered in this vascular brain malformation.

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“…49,50 Imaging studies are indicated only for the evaluation of suspected congenital anomalies. 49,51 In 2009 some Authors proposed diagnostic criteria for CMTG based on the presence of all three major criteria and at least two or more minor criteria. (Table 2) However, the diagnostic validity of these criteria has not been confirmed yet and further studies are needed for this purpose.…”

Section: Discussionmentioning

confidence: 99%

Cutis Marmorata Telangiectatica Congenita in a Preterm Female Newborn: Case Report and Review of the Literature

et al. 2014

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RiassuntoLa Cutis Marmorata Telangiectatica Congenita (CMTC) è una condizione rara, di solito presente alla nascita, caratterizzata da cutis marmorata persistente, localizzata o generalizzata, telangectasia e flebectasia. Riportiamo il caso di una neonata pretermine, terzogenita di genitori caucasici non consanguinei, con CMTC alla nascita che mostrava le tipiche lesioni cutanee e glaucoma congenito monolaterale. La patogenesi di questo disordine non è nota e la causa è probabilmente multifattoriale. Come fattori etiologici sono stati ipotizzati l'esposizione ad agenti teratogeni ed un meccanismo di trasmissione autosomico dominante a penetranza incompleta. La prognosi, nei casi senza complicazioni, è buona. AbstractCutis Marmorata Telangiectatica Congenita (CMTC) is a rare, sporadic condition usually present at birth characterized by localized or generalized persistent cutis marmorata, telangiectasia and phlebectasia. We report a preterm female newborn, the third child of non-related caucasian parents, with CMTC at birth who showed typical cutaneous features and monolateral congenital glaucoma. The pathogenesis of this disorder is unknown and the cause is probably multifactorial.Teratogens and autosomal dominant mode of inheritance with incomplete penetrance have been considered as etiological factors. Prognosis, in uncomplicated cases, is good. Case reportM.R. is a female newborn spontaneously delivered at 33 weeks and 5 days of gestational age (GA) for maternal preeclampsia. The baby needed no resuscitation at birth. Apgar score was 9-9 at 1' and 5' minutes of life respectively. Family medical history was noncontributory. During first hours of life, for incoming of respiratory distress syndrome, exogenous porcine surfactant was administered and mechanical ventilation performed for about 24 hours. Hypoglycemia was corrected by infusion of 10% glucose solution through umbilical venous catheter. Since birth marbled bluish and deep purple reticulated skin lesions involving the whole body were noted. The lesions were prominent over the trunk and face but more pronounced over the limbs and became more visible with crying and exposure to room temperature (Fig.1). Clinical characteristics and persistence of cutis marmorata prompted the diagnosis of Cutis Marmorata Telangiectatica Congenita (CMTC). The baby had normal face, head circumference 32.5 cm (90° percentile), birth weight 2,688 Kg (>97° percentile), length 48 cm (>97° percentile), without other vascular anomalies or asymmetry of limbs growth. Neurological examination showed mild hypotonia of the trunk, poor spontaneous motor activity, autonomic instability and immaturity of the organization of behavioral states, while ophthalmological evaluation detected unilateral congenital glaucoma in the left eye. Cardiac examination, audiologic screening, Magnetic Resonance Imaging (MRI) and abdominal ultrasound were normal. At four month of life, under general anesthesia, she underwent surgical trabeculotomy ab externo in the left eye with uneventful postoperative cours...

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Macrocephaly–capillary malformation: Analysis of 13 patients and review of the diagnostic criteria

Cited by 60 publications

References 26 publications

Megalencephaly Syndromes and Activating Mutations in the PI3K‐AKT Pathway: MPPH and MCAP

Megalencephaly Syndromes and Activating Mutations in the PI3K‐AKT Pathway: MPPH and MCAP

Severe holocord syrinx in a child with megalencephaly-capillary malformation syndrome

Cutis Marmorata Telangiectatica Congenita in a Preterm Female Newborn: Case Report and Review of the Literature

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