Macrocephaly-capillary malformation: Difference between revisions

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{{Short description|A genetic disorder characterized by overgrowth and vascular anomalies}}
{{Infobox medical condition (new)
{{Infobox medical condition (new)
| name            = Macrocephaly-capillary malformation
| name            = Macrocephaly-capillary malformation
| synonyms        = Macrocephaly-cutis marmorata telangiectatica congenita syndrome, Megalencephaly-cutis marmorata telangiectatica congenita syndrome
| synonyms        = Macrocephaly-cutis marmorata telangiectatica congenita syndrome, Megalencephaly-cutis marmorata telangiectatica congenita syndrome, M-CM syndrome, MCAP
| image          = A new born child with m-cm syndrome..png
| image          = A new born child with m-cm syndrome..png
| alt            =  
| alt            =  
| caption        = A newborn child with M-CM syndrome. A port-wine stain is visible under the nose. On the right side of a cheek, a capillary malformations are present.
| caption        = A newborn child with M-CM syndrome. A port-wine stain is visible under the nose. On the right side of the cheek, capillary malformations are present.
| pronounce      =  
| pronounce      =  
| field          =  
| field          = [[Medical genetics]], [[Pediatrics]], [[Neurology]]
| geneReviewsID  =  
| geneReviewsID  = mcap
| symptoms        =  
| symptoms        = [[Macrocephaly]], [[capillary malformations]], [[developmental delay]], [[hypotonia]], [[connective tissue]] abnormalities, [[asymmetry]], [[brain overgrowth]], [[polymicrogyria]], [[syndactyly]]
| complications  =  
| complications  = [[Seizures]], intellectual disability, overgrowth syndromes, risk of [[hydrocephalus]]
| onset          =  
| onset          = Congenital
| duration        =  
| duration        = Lifelong
| types          =  
| types          = Overgrowth syndrome
| causes          =  
| causes          = Somatic mutations in the [[PIK3CA]] gene
| risks          =  
| risks          = Sporadic; not usually inherited
| diagnosis      =  
| diagnosis      = Clinical examination, [[MRI]], [[genetic testing]]
| differential    =  
| differential    = [[Klippel–Trénaunay syndrome]], [[Proteus syndrome]], [[Sturge–Weber syndrome]], other [[PIK3CA-related overgrowth spectrum]] conditions
| prevention      =  
| prevention      = None
| treatment      =  
| treatment      = Supportive and symptomatic; includes [[physical therapy]], [[occupational therapy]], seizure management
| medication      =  
| medication      = [[Anticonvulsants]] for seizures; investigational targeted therapies (e.g. PI3K inhibitors)
| prognosis      =  
| prognosis      = Variable; depends on severity of symptoms and complications
| frequency      =  
| frequency      = Rare; estimated fewer than 1 in 1,000,000 live births
| deaths          =  
| deaths          = Rare; typically related to neurological complications
}}
}}


'''Macrocephaly-capillary malformation''' ('''M-CM''') is a multiple malformation syndrome causing abnormal body and head overgrowth and [[cutaneous]], [[vascular]], [[neurologic]], and limb abnormalities. Though not every patient has all features, commonly found signs include [[macrocephaly]], congenital [[macrosomia]], extensive cutaneous capillary malformation ([[naevus flammeus]] or [[port-wine stain]] type birthmark over much of the body; a capillary malformation of the upper lip or philtrum is seen in many patients with this condition), body asymmetry (also called hemihyperplasia or [[hemihypertrophy]]), [[polydactyly]] or [[syndactyly]] of the hands and feet, lax joints, doughy skin, variable [[developmental delay]] and other neurologic problems such as [[seizures]] and [[low muscle tone]].
'''Macrocephaly-capillary malformation''' (M-CM) is a rare [[genetic disorder]] characterized by a combination of [[macrocephaly]], [[capillary malformation]], and other distinctive features. It is also known as macrocephaly-capillary malformation syndrome (M-CM syndrome) or macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC).


==Genetics==
==Clinical Features==


Mosaic mutations in [[PIK3CA]] have been found to be the genetic cause of M-CM.<ref name="Rivière-2012">{{Cite journal  | last1 = Rivière | first1 = JB. | last2 = Mirzaa | first2 = GM. | last3 = O'Roak | first3 = BJ. | last4 = Beddaoui | first4 = M. | last5 = Alcantara | first5 = D. | last6 = Conway | first6 = RL. | last7 = St-Onge | first7 = J. | last8 = Schwartzentruber | first8 = JA. | last9 = Gripp | first9 = KW. | last10 = Nikkel | first10 = Sarah M | last11 = Worthylake | first11 = Thea | last12 = Sullivan | first12 = Christopher T | last13 = Ward | first13 = Thomas R | last14 = Butler | first14 = Hailly E | last15 = Kramer | first15 = Nancy A | last16 = Albrecht | first16 = Beate | last17 = Armour | first17 = Christine M | last18 = Armstrong | first18 = Linlea | last19 = Caluseriu | first19 = Oana | last20 = Cytrynbaum | first20 = Cheryl | last21 = Drolet | first21 = Beth A | last22 = Innes | first22 = A Micheil | last23 = Lauzon | first23 = Julie L | last24 = Lin | first24 = Angela E | last25 = Mancini | first25 = Grazia M S | last26 = Meschino | first26 = Wendy S | last27 = Reggin | first27 = James D | last28 = Saggar | first28 = Anand K | last29 = Lerman-Sagie | first29 = Tally | last30 = Uyanik | first30 = Gökhan | title = De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes | journal = Nat Genet | volume = 44 | issue = 8 | pages = 934–40 | month =  | year = 2012 | doi = 10.1038/ng.2331 | pmid = 22729224 | display-authors = 8 | pmc = 3408813 }}</ref> Other overgrowth conditions with distinct phenotypes have also been found to be caused by mosaic mutations in PIK3CA. How different mutations in this gene result in a variety of defined clinical syndromes is still being clarified.<ref name="Kurek-2012">{{Cite journal  | last1 = Kurek | first1 = KC. | last2 = Luks | first2 = VL. | last3 = Ayturk | first3 = UM. | last4 = Alomari | first4 = AI. | last5 = Fishman | first5 = SJ. | last6 = Spencer | first6 = SA. | last7 = Mulliken | first7 = JB. | last8 = Bowen | first8 = ME. | last9 = Yamamoto | first9 = GL. | last10 = Kozakewich | first10 = Harry P.W. | last11 = Warman | first11 = Matthew L. | title = Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome | journal = American Journal of Human Genetics | volume = 90 | issue = 6 | pages = 1108–15 |date=Jun 2012 | doi = 10.1016/j.ajhg.2012.05.006 | pmid = 22658544 | display-authors = 8 | pmc = 3370283 }}</ref><ref name="Lee-2012">{{Cite journal  | last1 = Lee | first1 = JH. | last2 = Huynh | first2 = M. | last3 = Silhavy | first3 = JL. | last4 = Kim | first4 = S. | last5 = Dixon-Salazar | first5 = T. | last6 = Heiberg | first6 = A. | last7 = Scott | first7 = E. | last8 = Bafna | first8 = V. | last9 = Hill | first9 = KJ. | last10 = Collazo | first10 = Adrienne | last11 = Funari | first11 = Vincent | last12 = Russ | first12 = Carsten | last13 = Gabriel | first13 = Stacey B | last14 = Mathern | first14 = Gary W | last15 = Gleeson | first15 = Joseph G | title = De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly | journal = Nat Genet | volume = 44 | issue = 8 | pages = 941–5 | month =  | year = 2012 | doi = 10.1038/ng.2329 | pmid = 22729223 | display-authors = 8 | pmc = 4417942 }}</ref><ref name="Lindhurst-2012">{{Cite journal  | last1 = Lindhurst | first1 = MJ. | last2 = Parker | first2 = VE. | last3 = Payne | first3 = F. | last4 = Sapp | first4 = JC. | last5 = Rudge | first5 = S. | last6 = Harris | first6 = J. | last7 = Witkowski | first7 = AM. | last8 = Zhang | first8 = Q. | last9 = Groeneveld | first9 = MP. | last10 = Scott | first10 = Carol E | last11 = Daly | first11 = Allan | last12 = Huson | first12 = Susan M | last13 = Tosi | first13 = Laura L | last14 = Cunningham | first14 = Michael L | last15 = Darling | first15 = Thomas N | last16 = Geer | first16 = Joseph | last17 = Gucev | first17 = Zoran | last18 = Sutton | first18 = V Reid | last19 = Tziotzios | first19 = Christos | last20 = Dixon | first20 = Adrian K | last21 = Helliwell | first21 = Timothy | last22 = O'Rahilly | first22 = Stephen | last23 = Savage | first23 = David B | last24 = Wakelam | first24 = Michael J O | last25 = Barroso | first25 = Inês | last26 = Biesecker | first26 = Leslie G | last27 = Semple | first27 = Robert K | title = Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA | journal = Nat Genet | volume = 44 | issue = 8 | pages = 928–33 | month =  | year = 2012 | doi = 10.1038/ng.2332 | pmid = 22729222 | display-authors = 8 | pmc = 3461408 }}</ref> Mutations in PIK3CA have not been found in a non-mosaic state in any of these disorders, so it is unlikely that the conditions could be inherited.
Individuals with M-CM typically present with a range of clinical features, which may vary in severity. The hallmark features include:


==Diagnosis ==
* '''Macrocephaly''': An abnormally large head size, often present at birth or developing in early infancy.
* '''Capillary malformations''': These are flat, pink or red birthmarks, often referred to as "port-wine stains," that can occur anywhere on the body.
* '''Overgrowth''': Disproportionate overgrowth of one side of the body (hemihyperplasia) or generalized overgrowth.
* '''Developmental delay''': Many individuals experience delays in reaching developmental milestones.
* '''Hypotonia''': Decreased muscle tone, which can affect motor skills.
* '''Syndactyly''': Fusion of fingers or toes, which may be partial or complete.
* '''Polydactyly''': Extra fingers or toes.
* '''Connective tissue abnormalities''': Such as joint hypermobility or skin laxity.


Diagnosis is usually based on clinical observation. Various sets of criteria have been suggested to identify the disorder in an individual patient, all of which include macrocephaly and a number of the following: somatic overgrowth, cutis marmorata, midline facial birthmark, polydactyly/syndactyly, asymmetry (hemihyperplasia or hemihypertrophy), hypotonia at birth, developmental delay, connective tissue defect and frontal bossing.<ref name="pmid10710221">{{cite journal|vauthors=Franceschini P, Licata D, Di Cara G, Guala A, Franceschini D, Genitori L | title=Macrocephaly-Cutis marmorata telangiectatica congenita without cutis marmorata? | journal=American Journal of Medical Genetics | year= 2000 | volume= 90 | issue= 4 | pages= 265–9 | pmid=10710221 | doi = 10.1002/(SICI)1096-8628(20000214)90:4<265::AID-AJMG1>3.0.CO;2-S| url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=10710221 }}</ref><ref name="pmid10649789">{{cite journal|vauthors=Robertson SP, Gattas M, Rogers M, Adès LC | title=Macrocephaly--cutis marmorata telangiectatica congenita: report of five patients and a review of the literature. | journal=Clin Dysmorphol | year= 2000 | volume= 9 | issue= 1 | pages= 1–9 | pmid=10649789 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=10649789 | doi=10.1097/00019605-200009010-00001}}</ref> Currently no consensus exists about which diagnostic criteria are definitive and so evaluation by a medical geneticist or other clinician with familiarity with the syndrome is usually needed to provide diagnostic certainty. It is not clear if there are some features which are mandatory to make the diagnosis, but [[macrocephaly]] appears essentially universal though may not be congenital. The distinctive vascular abnormalities of the skin often fade over time, making the diagnosis challenging in older children with this condition.
==Genetics==


The brain can be affected in several ways in this syndrome. Some children are born with structural brain anomalies such as [[cortical dysplasia]] or [[polymicrogyria]]. While [[developmental delay]] is nearly universal in this syndrome it is variable in severity, with the majority having mild to moderate delays and a minority having severe cognitive impairment. Some patients are affected with a seizure disorder. [[White matter]] abnormalities on [[magnetic resonance imaging]] (MRI), suggesting a delay in white matter [[myelination]], is commonly seen in early childhood. Some patients may have asymmetry of the brain, with one side being noticeably larger than the other.
M-CM is caused by mutations in the [[PIK3CA]] gene, which plays a role in cell growth and division. These mutations are typically not inherited but occur as a de novo event, meaning they arise spontaneously in the affected individual. The condition is part of a group of disorders known as [[PIK3CA-related overgrowth spectrum]] (PROS).


One interesting phenomenon that seems very common in this syndrome is the tendency for disproportionate brain growth in the first few years of life, with crossing of percentiles on the head circumference growth charts. A consequence of this disproportionate brain growth appears to be a significantly increased risk of cerebellar tonsillar herniation (descent of the cerebellar tonsils through the [[foramen magnum]] of the skull, resembling a [[Arnold–Chiari malformation|Chiari]] I malformation neuroradiologically) and [[ventriculomegaly]]/[[hydrocephalus]].<ref name="pmid18000912">{{cite journal |vauthors=Conway RL, Pressman BD, Dobyns WB, Danielpour M, Lee J, Sanchez-Lara PA, etal | title=Neuroimaging findings in macrocephaly-capillary malformation: a longitudinal study of 17 patients. | journal=American Journal of Medical Genetics | year= 2007 | volume= 143A | issue= 24 | pages= 2981–3008 | pmid=18000912 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=18000912 | doi=10.1002/ajmg.a.32040 }}</ref> Such cerebellar tonsil herniation may occur in up to 70% of children with M-CM.
==Diagnosis==


The medical literature suggests that there is a risk of [[cardiac arrhythmias]] in early childhood.<ref name="pmid11477607">{{cite journal|vauthors=Yano S, Watanabe Y | title=Association of arrhythmia and sudden death in macrocephaly-cutis marmorata telangiectatica congenita syndrome. | journal=American Journal of Medical Genetics | year= 2001 | volume= 102 | issue= 2 | pages= 149–52 | pmid=11477607 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=11477607 |doi=10.1002/ajmg.1428 }}</ref><ref name="Kuint-">{{Cite journal  | last1 = Kuint | first1 = J. | last2 = Globus | first2 = O. | last3 = Ben Simon | first3 = GJ. | last4 = Greenberger | first4 = S. | title = Macrocephaly-capillary malformation presenting with fetal arrhythmia | journal = Pediatr Dermatol | volume = 29 | issue = 3 | pages = 384–6 | month =  | year =  2012| doi = 10.1111/j.1525-1470.2011.01677.x | pmid = 22329570 }}</ref> The cause for this is unknown. In addition, a variety of different congenital cardiac malformations have been reported in a small number of patients with this disorder.<ref name="Erener Ercan-2012">{{Cite journal  | last1 = Erener Ercan | first1 = T. | last2 = Oztunc | first2 = F. | last3 = Celkan | first3 = T. | last4 = Bor | first4 = M. | last5 = Kizilkilic | first5 = O. | last6 = Vural | first6 = M. | last7 = Perk | first7 = Y. | last8 = Islak | first8 = C. | last9 = Tuysuz | first9 = B. | title = Macrocephaly-Capillary Malformation Syndrome in a Newborn With Tetralogy of Fallot and Sagittal Sinus Thrombosis | journal = J Child Neurol | volume =  28| issue =  1| pages =  115–9|date=Mar 2012 | doi = 10.1177/0883073812439346 | pmid = 22451530  }}</ref><ref name="Dueñas-Arias-2009">{{Cite journal  | last1 = Dueñas-Arias | first1 = JE. | last2 = Arámbula-Meraz | first2 = E. | last3 = Frías-Castro | first3 = LO. | last4 = Ramos-Payán | first4 = R. | last5 = Quibrera-Matienzo | first5 = JA. | last6 = Luque-Ortega | first6 = F. | last7 = Aguilar-Medina | first7 = EM. | title = Tetralogy of Fallot associated with macrocephaly-capillary malformation syndrome: a case report and review of the literature | journal = Journal of Medical Case Reports | volume = 3 | issue = 1 | pages = 9215 |date=Sep 2009 | doi = 10.4076/1752-1947-3-9215 | pmid = 20210980 | pmc=2827170}}</ref>
Diagnosis of M-CM is based on clinical evaluation and the presence of characteristic features. Genetic testing can confirm the diagnosis by identifying mutations in the PIK3CA gene. Imaging studies, such as [[MRI]] or [[CT scan]], may be used to assess brain structure and identify any associated abnormalities.


Like other syndromes associated with disproportionate growth, there appears to be a slightly increased risk of certain types of childhood malignancies in M-CM (such as [[Wilms' tumor]]). However, the precise incidence of these malignancies is unclear.
==Management==


==Treatment==
There is no cure for M-CM, and treatment is symptomatic and supportive. Management may involve:


There is no cure for this condition. Treatment is supportive and varies depending on how symptoms present and their severity. Some degree of developmental delay is expected in almost all cases of M-CM, so evaluation for early intervention or special education programs is appropriate. Rare cases have been reported with no discernible delay in academic or school abilities.
* Regular monitoring of head growth and development.
* Physical and occupational therapy to address motor delays and hypotonia.
* Surgical intervention for syndactyly or polydactyly if necessary.
* Educational support for developmental delays.
* Monitoring for potential complications, such as seizures or hydrocephalus.


[[Physical therapy]] and orthopedic bracing can help young children with gross motor development. [[Occupational therapy]] or [[speech therapy]] may also assist with developmental delays. Attention from an orthopedic surgeon may be required for leg length discrepancy due to hemihyperplasia.
==Prognosis==
 
Children with hemihyperplasia are thought to have an elevated risk for certain types of cancers. Recently published management guidelines recommend regular abdominal ultrasounds up to age eight to detect [[Wilms' tumor]]. AFP testing to detect liver cancer is not recommended as there have been no reported cases of [[hepatoblastoma]] in M-CM patients.<ref name="Rivière-2012"/>
 
Congenital abnormalities in the brain and progressive brain overgrowth can result in a variety of neurological problems that may require intervention. These include [[hydrocephalus]], cerebellar tonsillar herniation ([[Arnold–Chiari malformation|Chiari I]]), [[seizures]] and [[syringomyelia]]. These complications are not usually congenital, they develop over time often presenting complications in late infancy or early childhood, though they can become problems even later. Baseline brain and spinal cord MRI imaging with repeat scans at regular intervals is often prescribed to monitor the changes that result from progressive brain overgrowth.
 
Assessment of cardiac health with [[echocardiogram]] and [[EKG]] may be prescribed and arrhythmias or abnormalities may require surgical treatment.


==Prognosis==
The prognosis for individuals with M-CM varies depending on the severity of symptoms and associated complications. Early intervention and supportive therapies can improve quality of life and developmental outcomes.


Prognosis varies widely depending on severity of symptoms, degree of intellectual impairment, and associated complications. Because the syndrome is rare and so newly identified, there are no long term studies.
==Related pages==
==History ==


This disorder was recognized as a distinct syndrome in 1997 and named macrocephaly-cutis marmorata telangiectasia congenita or M-CMTC.<ref name="pmid9354837">{{cite journal |vauthors=Clayton-Smith J, Kerr B, Brunner H, Tranebjaerg L, Magee A, Hennekam RC, etal | title=Macrocephaly with cutis marmorata, haemangioma and syndactyly--a distinctive overgrowth syndrome. | journal=Clin Dysmorphol | year= 1997 | volume= 6 | issue= 4 | pages= 291–302 | pmid=9354837 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=9354837 | doi=10.1097/00019605-199710000-00001}}</ref><ref name="pmid9129744">{{cite journal |vauthors=Moore CA, Toriello HV, Abuelo DN, Bull MJ, Curry CJ, Hall BD, etal | title=Macrocephaly-cutis marmorata telangiectatica congenita: a distinct disorder with developmental delay and connective tissue abnormalities. | journal=American Journal of Medical Genetics | year= 1997 | volume= 70 | issue= 1 | pages= 67–73 | pmid=9129744 | doi = 10.1002/(SICI)1096-8628(19970502)70:1<67::AID-AJMG13>3.0.CO;2-V| url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=9129744 }}</ref>  A new name, macrocephaly-capillary malformation, abbreviated M-CM, was recommended in 2007.<ref name="pmid17963258">{{cite journal|vauthors=Toriello HV, Mulliken JB | title=Accurately renaming macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) as macrocephaly-capillary malformation (M-CM). | journal=American Journal of Medical Genetics | year= 2007 | volume= 143A | issue= 24 | pages= 3009 | pmid=17963258 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=17963258 | doi=10.1002/ajmg.a.31971 }}</ref>  This new name was chosen to more accurately describe the skin markings associated with this disorder. In January 2012, a paper proposed new names for the syndrome: megalencephaly-capillary malformation or megalencephaly-capillary malformation-polymicrogyria with an abbreviation of MCAP.<ref name="Mirzaa-2012">{{Cite journal  | last1 = Mirzaa | first1 = GM. | last2 = Conway | first2 = RL. | last3 = Gripp | first3 = KW. | last4 = Lerman-Sagie | first4 = T. | last5 = Siegel | first5 = DH. | last6 = deVries | first6 = LS. | last7 = Lev | first7 = D. | last8 = Kramer | first8 = N. | last9 = Hopkins | first9 = E. | last10 = Graham | first10 = John M. | last11 = Dobyns | first11 = William B. | title = Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis | journal = American Journal of Medical Genetics | volume = 158A | issue = 2 | pages = 269–91 |date=Feb 2012 | doi = 10.1002/ajmg.a.34402 | pmid = 22228622 | display-authors = 8 }}</ref>
* [[Genetic disorder]]
* [[Overgrowth syndrome]]
* [[PIK3CA-related overgrowth spectrum]]
* [[Capillary malformation]]


==References==
{{Reflist}}
<!-- Citations made with http://clinical.uthscsa.edu/cite/ -->


== External links ==
== External links ==
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[[Category:Syndromes]]
[[Category:Syndromes]]
[[Category:Human appearance]]
[[Category:Human appearance]]
{{dictionary-stub1}}
[[Category:Genetic disorders]]
== Macrocephaly-capillary malformation ==
[[Category:Congenital disorders]]
<gallery>
[[Category:Rare diseases]]
File:A_new_born_child_with_m-cm_syndrome..png|A new born child with M-CM syndrome.
</gallery>

Latest revision as of 04:14, 23 March 2025

A genetic disorder characterized by overgrowth and vascular anomalies


Macrocephaly-capillary malformation
Synonyms Macrocephaly-cutis marmorata telangiectatica congenita syndrome, Megalencephaly-cutis marmorata telangiectatica congenita syndrome, M-CM syndrome, MCAP
Pronounce
Field Medical genetics, Pediatrics, Neurology
Symptoms Macrocephaly, capillary malformations, developmental delay, hypotonia, connective tissue abnormalities, asymmetry, brain overgrowth, polymicrogyria, syndactyly
Complications Seizures, intellectual disability, overgrowth syndromes, risk of hydrocephalus
Onset Congenital
Duration Lifelong
Types Overgrowth syndrome
Causes Somatic mutations in the PIK3CA gene
Risks Sporadic; not usually inherited
Diagnosis Clinical examination, MRI, genetic testing
Differential diagnosis Klippel–Trénaunay syndrome, Proteus syndrome, Sturge–Weber syndrome, other PIK3CA-related overgrowth spectrum conditions
Prevention None
Treatment Supportive and symptomatic; includes physical therapy, occupational therapy, seizure management
Medication Anticonvulsants for seizures; investigational targeted therapies (e.g. PI3K inhibitors)
Prognosis Variable; depends on severity of symptoms and complications
Frequency Rare; estimated fewer than 1 in 1,000,000 live births
Deaths Rare; typically related to neurological complications


Macrocephaly-capillary malformation (M-CM) is a rare genetic disorder characterized by a combination of macrocephaly, capillary malformation, and other distinctive features. It is also known as macrocephaly-capillary malformation syndrome (M-CM syndrome) or macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC).

Clinical Features[edit]

Individuals with M-CM typically present with a range of clinical features, which may vary in severity. The hallmark features include:

  • Macrocephaly: An abnormally large head size, often present at birth or developing in early infancy.
  • Capillary malformations: These are flat, pink or red birthmarks, often referred to as "port-wine stains," that can occur anywhere on the body.
  • Overgrowth: Disproportionate overgrowth of one side of the body (hemihyperplasia) or generalized overgrowth.
  • Developmental delay: Many individuals experience delays in reaching developmental milestones.
  • Hypotonia: Decreased muscle tone, which can affect motor skills.
  • Syndactyly: Fusion of fingers or toes, which may be partial or complete.
  • Polydactyly: Extra fingers or toes.
  • Connective tissue abnormalities: Such as joint hypermobility or skin laxity.

Genetics[edit]

M-CM is caused by mutations in the PIK3CA gene, which plays a role in cell growth and division. These mutations are typically not inherited but occur as a de novo event, meaning they arise spontaneously in the affected individual. The condition is part of a group of disorders known as PIK3CA-related overgrowth spectrum (PROS).

Diagnosis[edit]

Diagnosis of M-CM is based on clinical evaluation and the presence of characteristic features. Genetic testing can confirm the diagnosis by identifying mutations in the PIK3CA gene. Imaging studies, such as MRI or CT scan, may be used to assess brain structure and identify any associated abnormalities.

Management[edit]

There is no cure for M-CM, and treatment is symptomatic and supportive. Management may involve:

  • Regular monitoring of head growth and development.
  • Physical and occupational therapy to address motor delays and hypotonia.
  • Surgical intervention for syndactyly or polydactyly if necessary.
  • Educational support for developmental delays.
  • Monitoring for potential complications, such as seizures or hydrocephalus.

Prognosis[edit]

The prognosis for individuals with M-CM varies depending on the severity of symptoms and associated complications. Early intervention and supportive therapies can improve quality of life and developmental outcomes.

Related pages[edit]


External links[edit]

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