case_images: PMC10484218_01
case_images: A Diffuse black to brownish lentigines seen mainly on the face of the proband (individual II-3). Ocular hypertelorism (asterisk), ptosis (arrowhead) and thick lips were remarkable. (B) Multiple lentigines over the anterior trunk and limbs varied in shape and size, and with diameters ranging from to 5 mm. (C) A cafe au lait macule (arrowhead) was seen on his mid-back. (D) Low set ears and retrognathism (arrowhead) were revealed. Echocardiography demonstrated (E) eccentric left ventricular hypertrophy (septal wall thickness: 22 mm, arrowhead), (F) without left ventricle outflow tract obstruction. (G,H) Cardiac magnetic resonance imaging showed hypertrophic segments over septal and apical walls (arrowhead).
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case_images: PMC10484218_01_fcvm-10-1225667-g001.jpg
case_images: F1
case_images: A 36-year-old male with a past history of bilateral congenital hearing loss presented to the dermatology clinic with diffuse black to brownish pigmented macules locating on his face, trunk and four limbs since early childhood, varying in shape and size, and with diameters ranging from 1 to 5 mm (Figures 1A-C). Cafe-au-lait macule was revealed (Figure 1C). Facial dysmorphic features including ocular hypertelorism, ptosis, thick lips (Figure 1A), retrognathism and bilateral low set ears (Figure 1D) were remarkable. Echocardiography demonstrated eccentric left ventricular hypertrophy (septal wall thickness: 22 mm) without outflow tract obstruction (Figures 1E,F, Supplementary Video S1). Cardiac magnetic resonance imaging revealed consistent findings with echocardiography (Figures 1G,H).
case_images: Pedigree of the proband (II-3, arrowhead). The black-filled squares and circle indicated the individuals with clinical evidence of NSML. Both proband (II-3), proband's mother (I-8), elder brother (II-2) and son (III-2) presented with multiple lentigines and facial dysmorphism. Clinical features of NSML were labelled with relevant symbols in the pedigree. Same heterozygous missense mutation of PTPN11 was confirmed in proband (II-3) and proband's son (III-2). Two unaffected family members (I-7 and III-1) showed no clinical evidence of NSML. Individual II-2 died at the age of 32 due to sudden cardiac death.
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case_images: F2
case_images: Echocardiography demonstrated normal left/right ventricle size and function, septal wall hypertrophy (maximal wall thickness: 17 mm) without left ventricle outflow tract obstruction (LVOTO) (Figure 3D and Supplementary Video S2), a secundum atrial septal defect (7 mm, shunting from left to right) (Figure 3E), and right pulmonary artery stenosis (peak pressure gradient around 14 mmHg) (Figure 3F).
case_images: PMC10484218_02
case_images: Pedigree of the proband (II-3, arrowhead). The black-filled squares and circle indicated the individuals with clinical evidence of NSML. Both proband (II-3), proband's mother (I-8), elder brother (II-2) and son (III-2) presented with multiple lentigines and facial dysmorphism. Clinical features of NSML were labelled with relevant symbols in the pedigree. Same heterozygous missense mutation of PTPN11 was confirmed in proband (II-3) and proband's son (III-2). Two unaffected family members (I-7 and III-1) showed no clinical evidence of NSML. Individual II-2 died at the age of 32 due to sudden cardiac death.
case_images: fcvm-10-1225667-g002.jpg
case_images: PMC10484218_02_fcvm-10-1225667-g002.jpg
case_images: F2
case_images: Echocardiography demonstrated normal left/right ventricle size and function, septal wall hypertrophy (maximal wall thickness: 17 mm) without left ventricle outflow tract obstruction (LVOTO) (Figure 3D and Supplementary Video S2), a secundum atrial septal defect (7 mm, shunting from left to right) (Figure 3E), and right pulmonary artery stenosis (peak pressure gradient around 14 mmHg) (Figure 3F).
case_images: (A) The proband's son (individual III-2) presented with diffuse lentigines over the face, thick lips and ocular hypertelorism. (B) Low set ears and (C) Diffuse lentigines over the trunk and pectus excavatum (arrowhead) were also revealed. Echocardiography showed (D) septal wall hypertrophy without intra-cavity or left ventricle outflow tract obstruction. (E) Secundum atrial septal defect (cross-mark) (defect size about 7 mm, shunting from left to right). (F) Narrowing color-flow at the right pulmonary artery, indicating right pulmonary artery stenosis.
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case_images: PMC10484218_03_fcvm-10-1225667-g003.jpg
case_images: F3
case_images: Echocardiography revealed eccentric septal hypertrophy (septal wall thickness: 26 mm) (Figure 4D), apical aneurysm and mid-cavity obstruction with pressure gradient (17 mmHg) (Figures 4E,F and Supplementary Video S3).
case_images: PMC10484218_03
case_images: (A) The proband's son (individual III-2) presented with diffuse lentigines over the face, thick lips and ocular hypertelorism. (B) Low set ears and (C) Diffuse lentigines over the trunk and pectus excavatum (arrowhead) were also revealed. Echocardiography showed (D) septal wall hypertrophy without intra-cavity or left ventricle outflow tract obstruction. (E) Secundum atrial septal defect (cross-mark) (defect size about 7 mm, shunting from left to right). (F) Narrowing color-flow at the right pulmonary artery, indicating right pulmonary artery stenosis.
case_images: fcvm-10-1225667-g003.jpg
case_images: PMC10484218_03_fcvm-10-1225667-g003.jpg
case_images: F3
case_images: Echocardiography revealed eccentric septal hypertrophy (septal wall thickness: 26 mm) (Figure 4D), apical aneurysm and mid-cavity obstruction with pressure gradient (17 mmHg) (Figures 4E,F and Supplementary Video S3).
case_images: (A) The proband's mother (individual I-8) presented with ocular hypertelorism and diffuse black to brownish facial lentigines. (B) Numerous lentigines on her back, varying in size and shape. (C) Close-up of back lentigines with diameters ranging from 1 mm to 5 mm. Echocardiography revealed (D) significant septal wall hypertrophy (septal wall thickness: 26 mm, cross-mark). (E) Apical aneurysm formation was revealed with midventricular obstruction. (F) Pulsed wave Doppler showed mid-cavity pressure gradient was around 17 mmHg.
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case_images: PMC10484218_03_fcvm-10-1225667-g004.jpg
case_images: F4
case_images: A 66-year-old woman with a history of diffuse lentigines since childhood (Figures 4A-C) came to the cardiology clinic with intermittent exertional dyspnea and exercise intolerance in the recent few months. Ocular hypertelorism was revealed (Figure 4A). Echocardiography revealed eccentric septal hypertrophy (septal wall thickness: 26 mm) (Figure 4D), apical aneurysm and mid-cavity obstruction with pressure gradient (17 mmHg) (Figures 4E,F and Supplementary Video S3).