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Microcephaly-capillary malformation syndrome(MICCAP)

MedGen UID:
481926
Concept ID:
C3280296
Disease or Syndrome
Synonym: MICCAP
SNOMED CT: Microcephaly-capillary malformation syndrome (703369003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): STAMBP (2p13.1)
 
Monarch Initiative: MONDO:0013659
OMIM®: 614261
Orphanet: ORPHA294016

Disease characteristics

Excerpted from the GeneReview: Microcephaly-Capillary Malformation Syndrome
The defining clinical characteristics of the microcephaly-capillary malformation (MIC-CAP) syndrome are typically present at birth: microcephaly and generalized cutaneous capillary malformations (a few to hundreds of oval/circular macules or patches varying in size from 1-2 mm to several cm), hypoplastic distal phalanges of the hands and/or feet, early-onset intractable epilepsy, and profound developmental delay. Seizures, which can be focal, tonic, and complex partial and can include infantile spasms, appear to stabilize after age two years. Myoclonus of the limbs and eyelids is common; other abnormal movements (dyskinetic, choreiform) may be seen. To date, the diagnosis has been confirmed in 18 individuals from 15 families. [from GeneReviews]
Authors:
Melissa T Carter  |  Ghayda Mirzaa  |  Laura M McDonell, et. al.   view full author information

Additional descriptions

From OMIM
The microcephaly-capillary malformation syndrome is a congenital disorder characterized by severe progressive microcephaly, early-onset refractory epilepsy, profound developmental delay, and multiple small capillary malformations spread diffusely on the body. Additional more variable features include dysmorphic facial features, distal limb abnormalities, and mild heart defects (summary by Carter et al., 2011 and Mirzaa et al., 2011).  http://www.omim.org/entry/614261
From MedlinePlus Genetics
Microcephaly-capillary malformation syndrome is an inherited disorder characterized by an abnormally small head size (microcephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).

In people with microcephaly-capillary malformation syndrome, microcephaly begins before birth and is associated with an unusually small brain and multiple brain abnormalities. Affected individuals develop seizures that can occur many times per day and are difficult to treat (intractable epilepsy). The problems with brain development and epilepsy lead to profound developmental delay and intellectual impairment. Most affected individuals do not develop skills beyond those of a 1- or 2-month-old infant. For example, most children with this condition are never able to control their head movements or sit unassisted.

Capillary malformations are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations look like pink or red spots on the skin. People with microcephaly-capillary malformation syndrome are born with anywhere from a few to hundreds of these spots, which can occur anywhere on the body. The spots are usually round or oval-shaped and range in size from the head of a pin to a large coin.

Other signs and symptoms of microcephaly-capillary malformation syndrome include abnormal movements, feeding difficulties, slow growth, and short stature. Most affected individuals have abnormalities of the fingers and toes, including digits with tapered ends and abnormally small or missing fingernails and toenails. Some affected children also have distinctive facial features and an unusual pattern of hair growth on the scalp.  https://medlineplus.gov/genetics/condition/microcephaly-capillary-malformation-syndrome

Clinical features

From HPO
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Right ventricular hypertrophy
MedGen UID:
57981
Concept ID:
C0162770
Disease or Syndrome
In this case the right ventricle is more muscular than normal, causing a characteristic boot-shaped (coeur-en-sabot) appearance as seen on anterior- posterior chest x-rays. Right ventricular hypertrophy is commonly associated with any form of right ventricular outflow obstruction or pulmonary hypertension, which may in turn owe its origin to left-sided disease. The echocardiographic signs are thickening of the anterior right ventricular wall and the septum. Cavity size is usually normal, or slightly enlarged. In many cases there is associated volume overload present due to tricuspid regurgitation, in the absence of this, septal motion is normal.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Spastic tetraparesis
MedGen UID:
658719
Concept ID:
C0575059
Disease or Syndrome
Spastic weakness affecting all four limbs.
Delayed myelination
MedGen UID:
224820
Concept ID:
C1277241
Finding
Delayed myelination.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Infantile spasms
MedGen UID:
854616
Concept ID:
C3887898
Disease or Syndrome
Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
Extra-axial cerebrospinal fluid accumulation
MedGen UID:
868477
Concept ID:
C4022871
Finding
An increased amount of cerebrospinal fluid (CSF) in the subarachnoid space.
CNS hypomyelination
MedGen UID:
892446
Concept ID:
C4025616
Finding
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
Hypoplastic hippocampus
MedGen UID:
1388294
Concept ID:
C4476822
Congenital Abnormality
Underdevelopment of the hippocampus.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Hypoplasia of the maxilla
MedGen UID:
66804
Concept ID:
C0240310
Congenital Abnormality
Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Anatomical Abnormality
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Wide nose
MedGen UID:
140869
Concept ID:
C0426421
Finding
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Sloping forehead
MedGen UID:
346640
Concept ID:
C1857679
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
Capillary malformation
MedGen UID:
90955
Concept ID:
C0340803
Congenital Abnormality
A capillary malformation is a flat, sharply defined vascular stain of the skin. It may cover a large surface area or it may be scattered and appear as little islands of color. In a capillary maformation, the predominant vessels are small, slow-flow vessels (i.e., arterioles and postcapillary venules).
Abnormal hair whorl
MedGen UID:
481933
Concept ID:
C3280303
Finding
An abnormal hair whorl (that is, a patch of hair growing in the opposite direction of the rest of the hair).
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMicrocephaly-capillary malformation syndrome
Follow this link to review classifications for Microcephaly-capillary malformation syndrome in Orphanet.

Recent clinical studies

Etiology

McDonell LM, Mirzaa GM, Alcantara D, Schwartzentruber J, Carter MT, Lee LJ, Clericuzio CL, Graham JM Jr, Morris-Rosendahl DJ, Polster T, Acsadi G, Townshend S, Williams S, Halbert A, Isidor B, David A, Smyser CD, Paciorkowski AR, Willing M, Woulfe J, Das S, Beaulieu CL, Marcadier J; FORGE Canada Consortium, Geraghty MT, Frey BJ, Majewski J, Bulman DE, Dobyns WB, O'Driscoll M, Boycott KM
Nat Genet 2013 May;45(5):556-62. Epub 2013 Mar 31 doi: 10.1038/ng.2602. PMID: 23542699Free PMC Article

Diagnosis

Postma JK, Zambonin JL, Khouj E, Alyamani S, Graham JM Jr, Alkuraya FS, Kundell S, Carter MT
Am J Med Genet A 2022 Nov;188(11):3350-3357. Epub 2022 Aug 13 doi: 10.1002/ajmg.a.62936. PMID: 35962715
Wu F, Dai Y, Wang J, Cheng M, Wang Y, Li X, Yuan P, Liao S, Jiang L, Chen J, Yan L, Zhong M
Mol Med Rep 2019 Dec;20(6):5145-5151. Epub 2019 Oct 17 doi: 10.3892/mmr.2019.10757. PMID: 31638258Free PMC Article
Naseer MI, Sogaty S, Rasool M, Chaudhary AG, Abutalib YA, Walker S, Marshall CR, Merico D, Carter MT, Scherer SW, Al-Qahtani MH, Zarrei M
Am J Med Genet A 2016 Nov;170(11):3018-3022. Epub 2016 Aug 17 doi: 10.1002/ajmg.a.37845. PMID: 27531570
Faqeih EA, Bastaki L, Rosti RO, Spencer EG, Zada AP, Saleh MA, Um K, Gleeson JG
Am J Med Genet A 2015 Apr;167A(4):805-9. Epub 2015 Feb 18 doi: 10.1002/ajmg.a.36782. PMID: 25692795
Dyment DA, Sawyer SL, Warman-Chardon J, Boycott KM
Curr Neurol Neurosci Rep 2013 Aug;13(8):364. doi: 10.1007/s11910-013-0364-1. PMID: 23793931

Prognosis

Wu F, Dai Y, Wang J, Cheng M, Wang Y, Li X, Yuan P, Liao S, Jiang L, Chen J, Yan L, Zhong M
Mol Med Rep 2019 Dec;20(6):5145-5151. Epub 2019 Oct 17 doi: 10.3892/mmr.2019.10757. PMID: 31638258Free PMC Article
Faqeih EA, Bastaki L, Rosti RO, Spencer EG, Zada AP, Saleh MA, Um K, Gleeson JG
Am J Med Genet A 2015 Apr;167A(4):805-9. Epub 2015 Feb 18 doi: 10.1002/ajmg.a.36782. PMID: 25692795

Clinical prediction guides

Wu F, Dai Y, Wang J, Cheng M, Wang Y, Li X, Yuan P, Liao S, Jiang L, Chen J, Yan L, Zhong M
Mol Med Rep 2019 Dec;20(6):5145-5151. Epub 2019 Oct 17 doi: 10.3892/mmr.2019.10757. PMID: 31638258Free PMC Article
Faqeih EA, Bastaki L, Rosti RO, Spencer EG, Zada AP, Saleh MA, Um K, Gleeson JG
Am J Med Genet A 2015 Apr;167A(4):805-9. Epub 2015 Feb 18 doi: 10.1002/ajmg.a.36782. PMID: 25692795

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