Table 1

Other cardiocutaneous syndromes: genetics, cutaneous and cardiac manifestations, and other key findings

Other cardiocutaneous syndromes
Syndrome	Genetics	Cutaneous manifestations	Cardiac manifestations	Other key findings
Hutchinson-Gilford Progeria syndrome55–57	▸ Autosomal dominant sporadic ▸ C>T substitution at codon 608 of the lamin gene, LMNA (chromosome 1q) ▸ Aberrantly spliced, truncated Lamin A=progerin ▸ Role in nuclear structure, gene expression, cell cycle regulation, apoptosis ▸ Progerin causes p53-mediated effect on shortening telomeres, thus early senescence	▸ Premature ageing (starts within first year of life) ▸ Characteristic ‘plucked bird’ appearance ▸ Atrophic skin ▸ Decreased subcutaneous fat ▸ Sclerodermoid features ▸ Mottled hyperpigmentation ▸ Diffuse alopecia ▸ Prominent scalp veins	▸ Myocardial infection ▸ Stroke ▸ Cause of death	▸ Short lifespan ▸ Midface hypoplasia ▸ Micrognathia ▸ Prominent eyes ▸ Protruding ears with absent earlobes ▸ Delayed dentition ▸ Short stature ▸ Lack of sexual maturation ▸ Thin limbs ▸ Prominent abdomen ▸ Stiff joints ▸ Prominent kyphosis
Arrhythmogenic Right Ventricular Cardiomyopathy58 59 (excluding Naxos–Carvajal)	▸ Autosomal dominant and recessive mutations in PKP (plakophilins) ▸ Autosomal dominant mutations in DSP (desmoplakin)	▸ Skin fragility to severe ectodermal dysplasia	▸ Fibro-fatty replacement of right ventricular myocardium ▸ Right ventricular dilation ▸ Ventricular arrhythmias ▸ Sudden cardiac death ▸ Presenting symptoms: chest pain, palpitations, dizziness, fatigue, syncope ▸ May have biventricular failure
Striate palmoplantar keratoderma60	▸ DSP haploinsufficiency	▸ Severe keratoderma ▸ Skin fragility ▸ Woolly hair ▸ Alopecia	▸ Arrhythmogenic cardiomyopathy
Severe Generalised Dystrophic Epidermolysis Bullosa61 62	▸ Autosomal dominant and recessive mutations in collagen COL7A1	▸ Generalised blistering ▸ Poorly healing wounds ▸ Extensive scarring	▸ Cardiomyopathy
Williams syndrome63 64	▸ Elastin gene haploinsufficiency due to a deletion at chromosome 7q detected by fluorescent in situ hybridisation	▸ Soft and lax skin ▸ Hypoplastic nails	▸ Supravalvular aortic stenosis ▸ Pulmonary stenosis ▸ Mitral valve regurgitation ▸ Arterial hypertension	▸ Growth delay ▸ Middle ear infections ▸ Interest and enthusiasm for music (almost universal) ▸ Mental retardation ▸ Overly friendly, sociable, inattentive, hyperactive ▸ Hyperacusis
Turner syndrome65 66	▸ Monosomy X	▸ Hypoplastic or hyperconvex nails (rarely seen in other syndromes) ▸ Excess nevi ▸ Loose skin folds (especially neck in neonates)	▸ Hypertension ▸ Aortic coarctation ▸ Hypoplastic left heart ▸ Bicuspid aortic valve ▸ Aortic dissection	▸ Short stature ▸ Webbed neck ▸ High arched palate ▸ Normal pubic hair ▸ Ovarian failure ▸ Cubitus valgus ▸ Shield chest ▸ Lympheodema
Down syndrome67 68	▸ Trisomy 21	▸ Xerosis ▸ Localised hyperkeratotic lesions ▸ Elastosis serpiginosa ▸ Alopecia areata ▸ Vitiligo ▸ Folliculitis ▸ Abscess formation ▸ Recurrent skin infections	▸ Endocardial cushion defect (atrioventricular septal defect/atrioventricular canal defect) ▸ Ventricular septal defect ▸ Secundum atrial septal defect ▸ Tetralogy of Fallot ▸ Isolated patent ductus arteriosus	▸ Single transverse palmar crease ▸ Fla occiput and flattened facies ▸ Epicanthal folds ▸ Upward palpebral fissures ▸ Small nose and mouth ▸ Protruding tongue ▸ Wide space between first and second toes (sandal gap)
▸ Refsum69 70	▸ Phytanoyl-coenzyme A hydroxylase deficiency	▸ Ichthyosis: small white scales on extensor surfaces of the trunk and extremities	▸ Cardiac arrhythmias (most common cause of death) ▸ Heart failure due to cardiomyopathy	▸ Anosmia ▸ Early onset retinitis pigmentosa ▸ Neuropathy ▸ Deafness ▸ Ataxia
▸ CHIME syndrome ▸ (Zunich Neuroectodermal syndrome)71–73	▸ Mutations in the glycosylphosphatidylinositol gene PIGL Chromosome 17	▸ Migratory ichthyosiform dermatosis ▸ Thick and dry skin at birth ▸ Pruritus during first months of life ▸ Trichorrhexis nodosa (50%)	▸ Pulmonary stenosis ▸ Ventricular septal defect ▸ Transposition of great vessels ▸ Tetralogy of Fallot	▸ Brachydactyly (all patients) ▸ Colobomas (mostly retinal) ▸ Mental retardation ▸ Ear anomalies ▸ Hypertelorism ▸ Broad flat nasal ridge ▸ Upslanting palpebral fissures ▸ Cupped ears ▸ Macrostomia with full lips