Cartilage-hair hypoplasia-anauxetic dysplasia spectrum disorders harboring RMRP mutations in two Korean children: A case report.

RATIONALE: Cartilage-hair hypoplasia (CHH, OMIM # 250250) is a rare autosomal recessive disorder, which includes cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders. CHH-AD is caused by homozygous or compound heterozygous mutations in the RNA component of the mitochondrial RNA-processing Endoribonuclease (RMRP) gene. PATIENT CONCERNS: Here, we report 2 cases of Korean children with CHH-AD. DIAGNOSES: In the first case, the patient had metaphyseal dysplasia without hypotrichosis, diagnosed by whole exome sequencing (WES), and exhibited only skeletal dysplasia and lacked extraskeletal manifestations, such as hair hypoplasia and immunodeficiency. In the second case, the patient had skeletal dysplasia, hair hypoplasia, and immunodeficiency, which were identified by WES. INTERVENTIONS: The second case is the first CHH reported in Korea. The patients in both cases received regular immune and lung function checkups. OUTCOMES: Our cases suggest that children with extremely short stature from birth, with or without extraskeletal manifestations, should include CHH-AD as a differential diagnosis. LESSONS SUBSECTIONS: Clinical suspicion is the most important and RMRP sequencing should be considered for the diagnosis of CHH-AD.

Extensive and deep granulomatous ulcers as an atypical manifestation of cartilage-hair hypoplasia syndrome: A diagnostic and therapeutic challenge.

Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment.

[Genetic analysis of a child with Hypotrichosis simplex].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Hypotrichosis 14. METHODS: A child who had presented at the Henan Provincial People's Hospital on May 4, 2020 due to hair thinning was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples were collected from the child and her parents. Genomic DNA was extracted and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-old female, had presented with thin, soft lanugo-like hair which was easy to fall off. The child was found to harbor compound heterozygous missense variants of the LSS gene, namely c.1609G>A (p.V537M) in exon 17 and c.802T>G (p.F268V) in exon 8, which were respectively inherited from her father and mother. Both variant sites were highly conserved, though based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as variants of unknown significance (PM2_Supporting+PP3+PP4). CONCLUSION: The c.1609G>A (p.V537M) and c.802T>G (p.F268V) compound heterozygous variants of the LSS gene probably underlay the clinical phenotype in this patient.

[Bazex syndrome: a rare paraneoplastic disease]. / Síndrome de Bazex: una enfermedad paraneoplásica infrecuente.

Bazex syndrome is a paraneoplastic disorder most commonly linked to squamous cell carcinomas of the upper aerodigestive tract, followed by lung cancer and other malignancies. It manifests through three stages of skin involvement that mirror the tumor's progression. Remarkably, skin lesions precede tumor symptoms or diagnosis in two-thirds of cases, underscoring the crucial role of suspecting this condition as it can promptly reveal an underlying neoplasm. Treatment primarily focuses on addressing the root neoplasm, with recurrent skin lesions potentially indicating tumor relapse. In this context, we present a clinical case involving a male patient whose manifestation of this syndrome facilitated the timely diagnosis of lung adenocarcinoma. This case underscores the significance of understanding this uncommon syndrome and its link to cancer, enabling early and accurate oncological diagnosis.

El síndrome de Bazex es una enfermedad paraneoplásica que se asocia con mayor frecuencia a carcinomas de células escamosas del tracto aerodigestivo superior, seguido en frecuencia por el cáncer de pulmón y otras neoplasias. Afecta a la piel en tres etapas que tienen un comportamiento paralelo al crecimiento del tumor. En dos tercios de los casos, las lesiones cutáneas preceden a los síntomas o al diagnóstico del tumor. De ahí la importancia de la sospecha de esta entidad, que puede desenmascarar a la neoplasia asociada en una etapa temprana. Su tratamiento consiste en tratar la neoplasia subyacente. La recurrencia de las lesiones cutáneas puede revelar la recaída del tumor. Comunicamos el caso clínico de un paciente de sexo masculino en el cual el hallazgo de este síndrome permitió realizar el diagnóstico de un adenocarcinoma de pulmón, lo cual destaca la importancia de conocer a esta rara enfermedad y su asociación con cáncer, para poder realizar el diagnóstico oncológico de forma temprana y oportuna.

A case of congenital cataracts with hypotrichosis caused by compound heterozygous variants in the LSS gene.

BACKGROUND: Patients with biallelic variants in the lanosterol synthase (LSS) gene has been reported to exhibit phenotypes as follows: non-syndromic form of hypotrichosis, congenital cataracts, and alopecia with intellectual disability or growth retardation. However, genotype-phenotype correlations in the LSS gene are still not completely clear. METHODS: In this study, we reported a Chinese girl who had congenital cataracts with hypotrichosis. The trio exome sequencing was performed to elucidate the genetic cause of the patient. RESULTS: We identified compound heterozygous variants (c.296G>A, p.G99D and c.1025T>G, p.I342S) in the LSS gene. Both variants altered the amino acid coding at highly conserved amino acid residues and were predicted to be deleterious using prediction software. CONCLUSION: Our report expands the spectrum of variants in the LSS gene and will be helpful for genotype-phenotype correlations study.

Autism spectrum disorder in a patient with Nicolaides-Baraitser Syndrome: case report.

Nicolaides-Baraitser Syndrome is a rare genetic condition that clinically presents with intellectual disabilities, facial and bone changes, and sparse hair. In Brazil, only one case has been previously reported without genetic confirmation. We present the case of an 8-year-old boy, clinically and genetically diagnosed with Nicolaides-Baraitser Syndrome, who developed autism spectrum disorder characteristics with a formal diagnosis at the age of eight. Diagnosing autism spectrum disorder in patients with intellectual disabilities is a clinical challenge requiring careful evaluation.

A case of LSS-associated congenital nuclear cataract with hypotrichosis and literature review.

Congenital cataract is the most common cause of lifelong visual loss in children worldwide, which has significant genotypic and phenotypic heterogeneity. The LSS gene encodes lanosterol synthase (LSS), which acts on the cholesterol biosynthesis pathway by converting (S)-2,3-oxidosqualene to lanosterol. The biallelic pathogenic variants in the LSS gene were found in congenital cataract, Alopecia-intellectual disability syndrome, hypotrichosis simplex, and mutilating palmoplantar keratoderma. In this study, we reported the first congenital nuclear cataract combined with hypotrichosis in a 12-year-old boy with biallelic LSS variants (c.1025T>G; p.I342S and c.1531_1532insT; p.L511Ffs*17) by exome sequencing. Reviewing all reported patients with LSS variants indicated that p.W629 might be a hotspot for hypospadias and p.I342S was associated with congenital cataract. Patients with one or two truncation variants tend to have multisystem symptoms compared with those with two missense variants. These findings deepen the understanding of LSS variants and contribute to the genetic counseling of affected families.

Comparative study of the efficacy and safety of topical minoxidil 2% versus topical bimatoprost 0.01% versus topical bimatoprost 0.03% in treatment of eyebrow hypotrichosis: a randomized controlled trial.

Eyebrows are an important feature of facial identity and communications in human beings as well as an important eye defense shield from dust and foreign bodies. To compare the efficacy and safety between 0.01%, 0.03% bimatoprost and minoxidil 2% in gel formulations for eyebrow enhancement. Sixty eligible subjects were female or male, aged 18 years or older with eyebrow hypotrichosis, defined as either a Grade 1 or 2 on the Global Eyebrow Assessment (GEBA) scale. Patients were randomized into 3 groups using block randomization. Group a (20 patients) applied topical 0.03% bimatoprost gel once daily onto both eyebrows, group b (20 patients) applied topical 0.01% bimatoprost gel once daily onto both eyebrows while group c (20 patients) applied topical minoxidil 2% gel once daily onto both eyebrows. A significant improvement in GEBA score was reported in all the three groups after treatment (P ≤ 0.001); however, there was no statistically significant difference between the three groups (P1 = 0.091; P2 = 0.102; P3 = 0.663). Bimatoprost is equally efficacious as minoxidil in enhancement of eyebrows with a more favorable response produced by the 0.03% concentration.

Non-syndromic hypotrichosis: A report of two novel variants in the LSS gene.

To date, more than 15 genes have been linked to syndromic and non-syndromic hypotrichosis, among which the LSS gene encoding lanosterol synthase was recently linked to autosomal recessive isolated hypotrichosis. Here we report the case of a 6-year-old girl born to non-consanguineous Iraqi parents and presenting with sparse lanugo hair since birth on the scalp, eyelashes, and eyebrows. Whole exome sequencing followed by Sanger sequencing allowed the detection of two novel compound heterozygous variants in LSS (p.Ile323Thr and p.Gly600Val). Reporting and investigating further cases with LSS variants might help establishing a better genotype-phenotype correlation.

Identification of a novel sporadic U2HR pathogenic variant in a patient with Marie Unna hereditary hypotrichosis.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant hair loss disorder characterized by coarse, wiry, and twisted hair developing during early childhood, and followed by progressive hair loss with puberty. We report a sporadic case of a 4-year-old boy with clinical features suggestive of MUHH, in whom we identified the new pathogenic variant c.67C>T; p.(Gln23*) in U2HR. This finding extends the known spectrum of U2HR variants underlying MUHH and increases genetic information for further genotype-phenotype correlation.