Diffuse neurofibroma with hypertrichosis in a toddler.

Diffuse neurofibroma is a rare type of neurofibroma uncommonly reported in infancy. It is a slow growing tumor originating in the peripheral nerve sheath. We present the case of a 17-month-old boy with diffuse neurofibroma of the scalp associated with hypertrichosis. His genetic and clinical workup for neurofibromatosis was negative.

Multiple vascular anomalies and refractory pericardial effusion in a young patient with Cantu syndrome: a case report and review of the literature.

BACKGROUND: Cantu syndrome is a rare and complex multisystem disorder characterized by hypertrichosis, facial dysmorphism, osteochondroplasia and cardiac abnormalities. With only 150 cases reported worldwide, Cantu syndrome is now gaining wider recognition due to molecular testing and a growing body of literature that further characterizes the syndrome and some of its most important features. Cardiovascular pathology previously described in the literature include cardiomegaly, pericardial effusion, vascular dilation and tortuosity, and other congenital heart defects. However, cardiovascular involvement is highly variable amongst individuals with Cantu syndrome. In some instances, it can be extensive and severe requiring surgical management and long term follow up. CASE PRESENTATION: Herein we report a case of a fourteen-year-old female who presented with worsening pericardial effusion of unknown etiology, and echocardiographic findings of concentric left ventricular hypertrophy, a mildly dilated aortic root and ascending aorta. Her medical history was notable for hemoptysis and an episode of pulmonary hemorrhage secondary to multiple aortopulmonary collaterals that were subsequently embolized in early childhood. She was initially managed with Ibuprofen and Colchicine but continued to worsen, and ultimately required a pericardial window for the management of refractory pericardial effusion. Imaging studies obtained on subsequent visits revealed multiple dilated and tortuous blood vessels in the head, neck, chest, and pelvis. A cardiomyopathy molecular studies panel was sent, and a pathogenic variant was identified in the ABCC9 gene, confirming the molecular diagnosis of autosomal dominant Cantu syndrome. CONCLUSIONS: Vascular anomalies and significant cardiac involvement are often present in Cantu syndrome, however there are currently no established screening recommendations or surveillance protocols in place. The triad of hypertrichosis, facial dysmorphism, and unexplained cardiovascular involvement in any patient should raise suspicion for Cantu syndrome and warrant further investigation. Initial cardiac evaluation and follow up should be indicated in any patient with a clinical and/or molecular diagnosis of Cantu syndrome. Furthermore, whole body imaging should be utilized to evaluate the extent of vascular involvement and dictate long term monitoring and care.

Milium cysts on hands; hypertrichosis on face.

The patient's dermatologic symptoms and his history of a particular chronic condition pointed toward the diagnosis.

Hair and Nail Conditions: Hypertrichosis and Hirsutism.

Hypertrichosis and hirsutism can be signs of underlying conditions, some of which may be life-threatening. They also can result in significant psychosocial distress for patients. Hypertrichosis refers to excessive hair growth beyond normal variation for a patient's age, sex, or race or for a particular body area. Hirsutism refers to an abnormal excess of hair growth solely in androgen-dependent areas of the body in females. The standard for hirsutism assessment is the modified Ferriman-Gallwey (mFG) score. Hirsutism can be idiopathic or associated with endocrine conditions, most commonly polycystic ovary syndrome (PCOS). Evaluation for underlying causes may be indicated depending on the clinical presentation. For premenopausal patients with an abnormal hirsutism score (ie, mFG score of 8 or greater), a serum total testosterone level should be obtained. If the level is normal in patients with moderate to severe hirsutism and/or evidence of a hyperandrogenic endocrine condition, an early morning serum total testosterone level and a free testosterone level should be obtained. An elevated total testosterone level indicates a hyperandrogenic state, and further testing is needed to determine if this is due to PCOS or another endocrine condition. Hair removal options for patients with hirsutism include temporary methods, electrolysis, and laser treatments. Pharmacotherapies include topical creams, combination oral contraceptives, and antiandrogens. Referral to an endocrinologist may be indicated if an underlying endocrine condition is suspected.

Cantù syndrome: Report of a patient with a novel variant in KCNJ8 and revision of literature.

Cantù syndrome (CS) is a rare multisystemic disorder, characterized by congenital hypertrichosis, macrocephaly, facial dysmorphisms, cardiomegaly, vascular, and skeletal anomalies. From the cognitive point of view, most of the patients show a mild speech delay and a few of them present intellectual disability and learning difficulties. To date, most CS-reported cases are caused by heterozygous ABCC9 gene mutations. Only three patients with CS and heterozygous KCNJ8 gene variants have been reported. The authors here present the fourth case of CS with a variant in KCNJ8 in a 6-month-old baby. Diagnosis was reached through Trio-Whole Exome analysis that revealed a de novo missense variant in KCNJ8.

Diverse clinical manifestations of Cantú syndrome: The first case series in Vietnam.

Cantú syndrome (CS) is an extremely rare autosomal dominant hereditary disease characterized by congenital hypertrichosis, distinct coarse facial features, cardiac defects, and other abnormalities in the skeletal and neurological systems. At present, cases with pathognomonic clinical manifestations are increasingly confirmed by genetic analysis. Two causative genes for CS are the well-known ABCC9 and the more rarely reported KCNJ8. Here, we report three Vietnamese children with CS, confirmed through genetic testing, presenting de novo ABCC9 mutations. The patients shared some common clinical manifestations, including congenital hypertrichosis, distinctive facial features, and a history of polyhydramnios during pregnancy. Concerning the various cardiac and neurological problems in the lifetime of patients with CS, an accurate diagnosis and appropriate management, especially genetic counseling, should be clinically applied in CS. Thus, our findings might modestly contribute to the global CS data, providing practical insights into CS manifestations.

Young adult with Cantú syndrome: dealing with a rare genetic skin disorder.

This case report of a young adult with Cantú syndrome (CS) illustrates a remarkable journey of learning how to cope with symptom management and emotional impact associated with a rare skin condition. We describe a 20-year-old woman with a CS-related mutation in ABCC9 resulting in clinical manifestations, including congenital hypertrichosis, facial dysmorphism and cardiomegaly. As of yet, no treatment is available for CS.Little is known about the impact of CS and similar (skin) conditions on the life of affected individuals, and about their needs and preferences in this regard. Hence, we describe the psychosocial implications our case had to deal with immediately after her diagnosis. In addition, we outline her significant progress in managing disease-associated features and emotional stress prompted by considerable personal development and an increase in confidence. This example shows that a normal lifestyle is achievable for (newly diagnosed) individuals despite suffering from CS or a related skin disorder.

Behavioral and cognitive functioning in individuals with Cantú syndrome.

Cantú syndrome (CS) is caused by pathogenic variants in ABCC9 and KCNJ8 encoding the regulatory and pore-forming subunits of ATP-sensitive potassium (KATP ) channels. CS is characterized by congenital hypertrichosis, distinctive facial features, peripheral edema, and cardiac and neurodevelopmental abnormalities. Behavioral and cognitive issues have been self-reported by some CS individuals, but results of formal standardized investigations have not been published. To assess the cognitive profile, social functioning, and psychiatric symptoms in a large group of CS subjects systematically in a cross-sectional manner, we invited 35 individuals (1-69 years) with confirmed ABCC9 variants and their relatives to complete various commonly applied standardized age-related questionnaires, including the Kaufman brief intelligence test 2, the social responsiveness scale-2, and the Achenbach system of empirically based assessment. The majority of CS individuals demonstrated average verbal and nonverbal intelligence compared to the general population. Fifteen percent of cases showed social functioning strongly associated with a clinical diagnosis of autism spectrum disorder. Both externalizing and internalizing problems were also present in this cohort. In particular, anxiety, anxiety or attention deficit hyperactivity disorder, and autism spectrum behaviors were predominantly observed in the younger subjects in the cohort (≥25%), but this percentage decreased markedly in adults.

Identification of Oliver-McFarlane syndrome caused by novel compound heterozygous variants of PNPLA6.

OBJECTIVES: Oliver-McFarlane syndrome (OMCS) is an autosomal recessive inherited disease resulting from PNPLA6 mutations that results in intellectual impairment and profound short stature. To obtain a better understanding of the genotype-phenotype correlations for PNPLA6-related disorders, we reported the 14th OMCS case and summarized all the reported cases of OMCS. METHODS: We collected clinical biochemical and data and brain MRI data and used whole-exon gene detection and analysis tools to evaluate the pathogenicity of the variants, including PolyPhen-2 and Mutation Taster, and we also generated three-dimensional protein structures and visualized the effects of altered residues with I-TASSER and PyMOL Viewer software. RESULTS: The patient presented with trichomegaly and multiple pituitary hormone deficiencies. Brain MRI showed small pituitary and bilateral paraventricular leukomalacia. Novel variants (c.1491G > T and c.3367G > A) in the PNPLA6 gene were detected in the proband and verified by direct sequencing. Amino acid residues of Gln497 and Gly1123 are predicted to be damaging and destroy the three-dimensional protein structures of the protein. In follow-up, this patient could neither walk nor hold his head erect and had not spoken one word at the age of one year and ten months. Moreover, there is no obvious hot spot mutation in any of the reported allelic variants. Interestingly, the majority of mutations are located in the phospholipid esterase domain, which is responsible for esterase activity. CONCLUSIONS: We identified two novel variants of the PNPLA6 gene in an OMCS patient, which will help to better understand the function of PNPLA6 and genotype-phenotype correlations for PNPLA6-related disorders.

Case of melorheostosis associated with ipsilateral verrucous epidermal nevus, linear connective tissue nevus, diffuse hyperpigmentation and hypertrichosis: A fortuitous coincidence?

Melorheostosis (MEL) is a rare benign bone disorder that can be associated with several anomalies, including vascular abnormalities, nevus sebaceus, unilateral nevoid telangiectasia, linear scleroderma and hypertrichosis. We report the case of a 6-year-old patient who showed an unusual co-occurrence of bone hyperostosis and different skin lesions affecting the same side of the body: MEL, verrucous epidermal nevus, connective tissue nevus, linear scleroderma-like disorder, hyperpigmentation and hypertrichosis. The spatial co-occurrence of these conditions made us speculate as to whether they originated from a common genetic mechanism or if their co-occurrence was completely accidental.

Wiedemann-steiner syndrome with a de novo mutation in KMT2A: A case report.

RATIONALE: Wiedemann-Steiner syndrome (WDSTS, online mendelian inheritance in man 605130) is a rare autosomal dominant disorder characterized by hypertrichosis cubiti. Here, we report a Chinese boy who do not show the characteristic of hypertrichosis cubiti, and was misdiagnosed as blepharophimosis-ptosis-epicanthus inversus syndrome at first. We found a de novo frameshift mutation (p.Glu390Lysfs*10) in the KMT2A gene, which was not reported before. Our study increases the cohort of Chinese WDSTS patients, and expand the WDSTS phenotypic and variation spectrum. PATIENT CONCERNS: The patient demonstrated typical craniofacial features of blepharophimosis-ptosis-epicanthus inversus syndrome, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus, besides he had congenital heart disease (ventricular septal defects), strabismus, hypotonia, amblyopia, delayed speech and language development, delayed psychomotor development, and amblyopia (HP:0000646) which was not reported before. DIAGNOSIS: FOXL2 gene was cloned and sequenced, however, there was no mutation detected in this patient. The result of Chromosomal microarray analysis was normal. The patient was diagnosed as WDSTS by whole exome sequencing. INTERVENTIONS: The patient received cardiac surgery, frontalis suspension and regular speech and occupational therapy. He also treated with growth hormone (GH). OUTCOMES: The patient's symptoms are improved after cardiac surgery and frontalis suspension, he can express himself well now and had a 10 cm gain in height. LESSONS: As the relationship between genotype and phenotype becomes more and more clear, WES is incredibly powerful tool to diagnose the disease of WDSTS.