INHERITANCE
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ARCL
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Phenotypes
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IA; MIM 219100
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IB; MIM 614437
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IC; MIM 613177
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IIA MIM 219200
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IIB MIM 612940
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IIC MIM 617402
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IID MIM 617403
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IIIA MIM 219150
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IIIB MIM 614438
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Genes
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FBLN5
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FBLN4
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LTBP4
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ATP6V0A2
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PYCR1
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ATP6V1E1
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ATP6V1A
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ALDH18A1
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PYCR1
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SKIN
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- Loose redundant skin
- Excessive skin folds
- Normal wound healing
- No skin hyperelasticity
- Increased vascularization, reduced collagen bundle size
- Underdeveloped elastic fibers in dermis
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- Velvety skin
- Normal scarring
- Collagen bundles smaller than normal
- Vascularization increased in upper dermis
- Underdeveloped elastic fibers, severe
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- Skin laxity
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- Loose redundant skin
- Excessive skin folds
- Abnormal, broken, shortened elastic fibers
- Decreased amount of elastin
- Sparse, brittle hair
- Coarse hair
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- Cutis laxa
- Loose redundant skin (especially of dorsum of hands and feet and anterior abdominal wall)
- Reduced skin elasticity
- Wrinkly skin
- Prominent veins
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- Generalized skin wrinkling
- Reduced elastic fibers
- Fragmented elastic fibers
- Loosely packed collagen fibers
- Variable diameters of collagen fibers
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- Generalized skin wrinkling
- Reduced elastic fibers
- Fragmented elastic fibers
- Loosely packed collagen fibers
- Variable diameters of collagen fibers
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- Thin, translucent skin
- Prominent superficial blood vessels due to thin skin
- Reduced number of elastic fibers
- Thin or fragmented elastic fibers
- Degenerated elastic fibers
- Sparse hair
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-Skin laxity
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CARDIOVASCULAR
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- Supravalvular aortic stenosis
- Vascular tortuosity
- Ascending aortic aneurysm
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Thickened myocardium (rare)
- Bradycardia (rare)
- Aortic aneurysm
- Pulmonary artery aneurysm
- Arterial aneurysms, multiple
- Arterial tortuosity, general
- Venous tortuosity
- Arterial stenoses, multiple
- Vascular fragility
- Vascularization increased in upper dermis
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- Pulmonary artery stenosis
- Patent foramen ovale
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- No vascular tortuosity
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- Severe dilation of ascending aortic root
- Moderate biventricular hypertrophy
- Mild dilation of right ventricle
- Reduced diastolic compliance of right ventricle
- Hypoplastic right ventricle
- Tricuspid valve stenosis
- Tricuspid insufficiency
- Aortic insufficiency
- Mitral valve prolapse
- Hypoplastic pulmonary artery
- Atrial septal defect
- Incomplete right bundle branch block
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- Atrial septal defect
- Dilated ascending aorta
- Tortuous aortic arch
- Cardiac failure
- Cardiomyopathy, hypertrophic
- Hypertrophy of interventricular septum, mild
- Long QT interval on electrocardiography (ECG)
- Incomplete right bundle branch block (ECG)
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RESPIRATORY
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- Recurrent respiratory infections
- Emphysema
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- Emphysema
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- Laryngomalacia
- Tracheomalacia
- Bronchomalacia
- Emphysema
- Hypoplastic lung
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- Laryngomalacia
- Bilateral pneumothorax (in early infancy)
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HEAD
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- Microcephaly
- Sagging cheeks
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- Microcephaly (rare)
- Prominent forehead
- Prominent premaxilla
- Micrognathia
- Dysplastic ears
- Low-set ears
- Prominent eyes
- Small palpebral fissures
- Downslanting palpebral fissures
- Hypertelorism, mild
- Bulbous nasal tip (in some patients)
- Hooked nose (in some patients)
- Depressed nasal bridge (in some patients)
- High-arched palate
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- Wide fontanels
- Micrognathia
- Flat midface
- Receding forehead
- Periorbital swelling
- Hypertelorism
- Wide nasal bridge
- Long philtrum
- Retrognathia
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- Microcephaly
- Midface hypoplasia
- Long philtrum
- Flat face
- Low-set ears
- Downslanting palpebral fissures
- Strabismus
- Myopia
- Short nose
- Anteverted nares
- Small mouth
- High-arched palate
- Dental caries
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- Microcephaly
- Large fontanel
- Broad, prominent forehead
- Sagging cheeks
- Aged appearance
- Triangular face
- Midface hypoplasia
- Prominent ears
- Blue sclerae
- Downslanting palpebral fissures (in 2 patients)
- Hypotelorism (in 2 patients)
- Deep-set eyes (in 2 patients)
- Prominent bulbous nose
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- Progeroid facies
- Mask-like triangular face
- Short forehead
- Long philtrum
- Prominent nasolabial folds
- Short pointed chin
- Low-set ears
- Misfolded helices
- Hypertelorism
- Entropion
- Nystagmus
- Prominent beaked nose
- High nasal root
- Broad nasal tip
- Broad columella
- Narrow nostrils
- High-arched palate
- Dental crowding
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- Progeroid facies
- Mask-like facies
- Triangular face
- Short forehead
- Receding chin
- Low-set ears
- Large ears
- Prominent ears
- Simple folded helices
- Hypertelorism
- Entropion
- Blepharophimosis
- Downslanting palpebral fissures
- Bilateral cataract
- Bulbous nose
- Broad nasal bridge
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- Brachycephaly
- Prominent forehead
- Large fontanelles
- Progeroid appearance
- Low-set ears
- Large ears
- Corneal opacities
- Cataracts
- Hypotelorism
- Hypertelorism
- Strabismus
- Myopia
- Salt-and-pepper retinopathy (in some patients)
- Pinched nose
- Hypoplastic alae
- Small mouth
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-Corneal opacification
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GENITOURINARY
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External Genitalia (Male)
- Inguinal hernia
External Genitalia (Female)
- Inguinal hernia
Bladder
- Bladder diverticula
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External Genitalia (Male)
- Inguinal hernia
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External Genitalia (Male)
- Inguinal hernia
Kidneys
- Hydronephrosis
Bladder
- Bladder diverticula
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External Genitalia (Male)
- Inguinal hernias, bilateral
Internal Genitalia (Male)
- Cryptorchidism, bilateral
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External Genitalia (Male)
- Micropenis
- Inguinal hernia
Internal Genitalia (Male)
- Cryptorchidism, bilateral
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Internal Genitalia (Male)
- Undescended testes (in some patients)
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MISCELLANEOUS
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- Relatively mild cutis laxa, associated with severe vascular abnormalities
- Massive aortic aneurysm can cause airway compression in affected infants
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- Skin abnormalities tend to decrease with age
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- One Kuwaiti and one Iranian family with 2 sibs each have been reported (last curated March 2017)
- Variable congenital heart defects
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- Based on 3 patients (last curated March 2017)
- Variable cardiac and skeletal features may be present
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SKELETAL
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- Congenital fractures
- Joint laxity
- Arachnodactyly
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- Joint hypermobility, generalized
- Fractures at birth
- Arachnodactyly
- Contractures of third to fifth fingers
- Arachnodactyly
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- Joint laxity
- Wide sutures
- Widely spaced first and second toes
- Plantar crease
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- Joint hyperextensibility
- Large anterior fontanel
- Delayed closure of the fontanel
- Congenital hip dislocation
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- Joint hyperextensibility
- Osteopenia
- Scoliosis (in 2 patients)
- Congenital hip dislocation
- Bowing of long bones
- Long digits (in 2 patients)
- Clasped thumb
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- Joint laxity
- Recurrent dislocations of temporomandibular joint
- Kyphoscoliosis
- Hip dysplasia
- Flexion contractures of knees
- Clenched hands
- Ulnar deviation of fingers
- Flat feet
- Club feet
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- Flexion contractures of all joints
- Dislocated hips
- Camptodactyly
- Club feet
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- Delayed bone age
- Hyperextensible joints
- Dislocated joints
- Wormian bones
- Wide cranial sutures
- Scoliosis
- Congenital hip dislocation
- Adducted thumbs
- Clenched fists
- Talipes equinovarus
- Pes calcaneovalgus
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- Congenital hip dislocation
- Patent anterior fontanelle
- Joint laxity
-Scoliosis
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ABDOMEN
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- Umbilical hernias
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- Umbilical hernia
- Gastroesophageal reflux
- Diverticula
- Pyloric stenosis
- Intestinal dilatation, tortuosity
- Rectal prolapsed
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- Feeding problems in infancy
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- Gastroesophageal reflux
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- Inguinal hernia
- Umbilical hernia
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Hernias
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NEUROLOGIC
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- Hypotonia
- Brain hemorrhage
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- Delayed motor development
- Mental retardation
- Seizures
- Hypotonia
- Partial pachygyria
- Cobblestone lissencephaly, posterior frontal and parietal regions
- Board and poorly defined gyri
- Polymicrogyria
- Dandy-Walker malformation
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- Developmental delay
- Agenesis of the corpus callosum (in 2 patients)
- Hydrocephalus (in 2 patients)
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- Hypotonia
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- Hypotonia
- Seizures
- Speech delay
- Motor delay
- Enlarged ventricles with white matter involvement
- Periventricular parietooccipital gliosis
- Diffuse thickening of cerebral cortex
- Thin corpus callosum
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- Developmental delay
- Hypotonia
- Athetoid movements
- Hyperreflexia
- Seizures
- Grimacing
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-Delayed motor development
-Mental retardation
-Hypotonia
-Athetoid movements
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Other
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- Fetal overgrowth
- Pectus excavatum
- Diaphragmatic hernia
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- Fetal overgrowth (in some patients)
- Pectus excavatum
- Hypoplastic diaphragm
- Diaphragmatic hernia
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- Postnatal growth delay
- Diaphragm hernia or eventration
- Low muscle tone
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- Intrauterine growth retardation (IUGR)
- Failure to thrive
- Hypotonia
- Lipodystrophy
- Abnormal distribution of subcutaneous fat
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- Intrauterine growth retardation
- Failure to thrive
- Poor postnatal growth
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- Short stature
- Low weight
- Marfanoid habitus
- Sparse subcutaneous fat
- Marked muscular atrophy
- Reduced muscular strength
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- Failure to thrive
- Marfanoid habitus
- Abnormal fat distribution
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- Intrauterine growth retardation (IUGR)
- Failure to thrive
- Poor postnatal growth
- Pectus excavatum
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-intrauterine growth retardation
-Postnatal growth delay
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