Identification of a founder effect involving n.197C>T variant in RMRP gene associated to cartilage-hair hypoplasia syndrome in Brazilian patients.

Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.71A>G), the most common RMRP variant worldwide. More than 130 pathogenic variants in this gene have already been described associated with CHH, and founder alterations were reported in the Finnish and Japanese populations. Our previous study in Brazilian CHH patients showed a high prevalence of n.197C>T variant (former n.195C>T and n.196C>T) when compared to other populations. The aim of this study was to investigate a possible founder effect of the n.197C>T variant in the RMRP gene in a series of CHH Brazilian patients. We have selected four TAG SNPs within chromosome 9 and genotyped the probands and their parents (23 patients previously described and nine novel). A common haplotype to the n.197C>T variant carriers was identified. Patients were also characterized for 46 autosomal Ancestry Informative Markers (AIMs). European ancestry was the most prevalent (58%), followed by African (24%) and Native American (18%). Our results strengthen the hypothesis of a founder effect for the n.197C>T variant in Brazil and indicate that this variant in the RMRP gene originated from a single event on chromosome 9 with a possible European origin.

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.

Altered oral microbiome, but normal human papilloma virus prevalence in cartilage-hair hypoplasia patients.

BACKGROUND: Cartilage-hair hypoplasia (CHH) is a rare syndromic immunodeficiency with metaphyseal chondrodysplasia and increased risk of malignancy. In this cross-sectional observational study, we examined HPV status and oral microbiome in individuals with CHH. Oral brush samples were collected from 20 individuals with CHH (aged 5-59 years) and 41 controls (1-69 years). Alpha HPVs (43 types) were tested by nested PCR followed by bead-based probe hybridization. Separately, beta-, gamma-, mu- and nu- HPV types were investigated, and a genome-based bacterial microbiome sequencing was performed. RESULTS: We found a similar alpha HPV prevalence in individuals with CHH (45%) and controls (36%). The HPV types of individuals with CHH were HPV-16 (25%), 27, 28, and 78, and of controls HPV-3, 16 (21%), 27, and 61. Beta HPV positivity and combined beta/gamma/mu/nu prevalence was detected in 11% and 11% of individuals with CHH and in 5% and 3% of the controls, respectively. Individuals with CHH differed from the controls in bacterial microbiota diversity, richness, and in microbial composition. Individuals with CHH had lower abundance of species Mitsuokella sp000469545, Parascardovia denticolens, Propionibacterium acidifaciens, UMGS1907 sp004151455, Salinicola halophilus, Haemophilus_A paraphrohaemolyticus, Fusobacterium massiliense, and Veillonella parvula, and higher abundance of Slackia exigua. CONCLUSIONS: Individuals with CHH exhibit similar prevalence of HPV DNA but different bacterial microbiota on their oral mucosa compared to healthy controls. This may partly explain the previously observed high prevalence of oral diseases in CHH, and regular oral examination is warranted.

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.

RMRP-related short stature: A report of six additional Japanese individuals with cartilage hair hypoplasia and literature review.

Biallelic pathogenic variants in RMRP, the gene encoding the RNA component of RNase mitochondrial RNA processing enzyme complex, have been reported in individuals with cartilage hair hypoplasia (CHH). CHH is prevalent in Finnish and Amish populations due to a founder pathogenic variant, n.71A > G. Based on the manifestations in the Finnish and Amish individuals, the hallmarks of CHH are prenatal-onset growth failure, metaphyseal dysplasia, hair hypoplasia, immunodeficiency, and other extraskeletal manifestations. Herein, we report six Japanese individuals with CHH from four families. All probands presented with moderate short stature with mild metaphyseal dysplasia or brachydactyly. One of them had hair hypoplasia and the other immunodeficiency. By contrast, the affected siblings of two families showed only mild short stature. We also reviewed all previously reported 13 Japanese individuals. No n.71A > G allele was detected. The proportions of Japanese versus Finnish individuals were 0% versus 70% for birth length < -2.0 SD, 84% versus 100% for metaphyseal dysplasia and 26% versus 88% for hair hypoplasia. Milder manifestations in the Japanese individuals may be related to the difference of genotypes. The mildest form of CHH phenotypes is mild short stature without overt skeletal alteration or extraskeletal manifestation and can be termed "RMRP-related short stature".

Pelo lanoso generalizado: reporte de un caso / Generalized woolly hair: case report

Introducción: El pelo lanoso (PL) es una rara alteración del tallo piloso que puede ser localizada o generalizada y puede asociarse a alteraciones cutáneas o extracutáneas. Objetivo: Analizar un cuadro clínico de muy escasa frecuencia y enfatizar la importancia del examen físico en el enfrentamiento de ésta. Caso clínico: Preescolar de tres años de edad con pelo fino, claro, corto y rizado. En los antecedentes familiares, destacaba la madre con historia de alopecia desde la infancia y disminución de la velocidad de crecimiento del pelo del cuero cabelludo; cuadro compatible con pelo lanoso generalizado forma hereditaria, sin anomalías asociadas. Conclusiones: El pelo lanoso es una rara anormalidad del tallo piloso. El diagnóstico de certeza se obtiene mediante la microscopía electrónica, sin embargo, el uso de la dermatoscopía constituye una buena herramienta diagnóstica en la práctica diaria. Puede asociarse a anomalías cutáneas y extracutáneas, por lo cual el enfrentamiento clínico y estudio complementario es primordial para descartar anomalías asociadas.

Introduction: Woolly hair (WH) is a rare abnormality of the hair shaft that can be localized or generalized and may be associated with cutaneous or extracutaneous abnormalities. Objective: To analyze a rare clinical case and emphasize the importance of physical examination. Case report: A three year old child with fine, light, short and curly hair is reported. Regarding family history, his mother reports alopecia since childhood and decreased growth rate of the hair of the scalp. The clinical picture is compatible with generalized hereditary woolly hair without associated anomalies. Conclusions: Woolly hair is a rare abnormality of the structure of the scalp hair. Electron microscopy allows the definitive diagnosis, however the use of dermoscopy is a practical and effective diagnostic tool in everyday practice.

Síndrome hipoplasia cartílago-cabello: reporte de caso / Cartilage-hair hypoplasia syndrome: a case report

El síndrome hipoplasia cartílago cabello también conocido como condrodisplasia Metafisiaria tipo Mc Kusickes una enfermedad autosómica recesiva que presenta múltiples manifestaciones fenotípicas, tales como talla baja con miembros cortos, alteraciones osteocondrales, extremidades cortas, vello corporal y cabello fino y escaso, piernas relativamente cortas con arqueamiento de los fémures, manos cortas y uñas pequeñas, defectos variables en la inmunidad celular y predisposición a una variedad de neoplasias. El manejo médico de estos pacientes requiere un enfoque multidisciplinario con especialistas en hematología, genética, nutrición y estomatología pediátrica. Se reporta el caso de un paciente con este síndrome al cual fue rehabilitado en el servicio de Odontopediatría del Departamento de Estomatología del Hospital Infantil de México Federico Gómez.

Kusick type is an autosomal recessive disease, has multiple phenotypic manifestations such as hypoplastic hair, short stature, osteochondral abnormalities, short limbs, fine and sparse hair, thin body hair scares relatively short legs with bow femurs, short hands and nails small defects in cellular immunity variables and predisposition to a variety of neoplasm. Management of these patients requires a multidisciplinary approach with specialists in hematology, genetics nutrition and pediatric dentistry. This case report describes phonotypical manifestations of patient with this syndrome who received dental treatment in the Pediatric Dentistry Service at Hospital Infantile de Mexico Federico Gómez .

Woolly hair generalizado: caso clínico e revisão da literatura / Generalized woolly hair: case report and literature review

O termo woolly hair, ou cabelo lanoso, refere-se a uma variante anormal de cabelo, que pode ser parcial ou generalizado. As variantes de woolly hair generalizado são raras e podem ocorrer isoladamente ou associadas a outras alterações cutâneas e extracutâneas. Desta forma, nestes doentes, é necessário a exclusão de certos síndromes, como o de Noonan e cardiofaciocutâneo (CFC), que cursam com importante morbilidade e mortalidade. É descrito o caso clínico de uma criança com woolly hair generalizado e queratose pilar, mas que, após avaliação dos vários órgãos e sistemas, não foi encontrada qualquer alteração ou característica associada a esses síndromes.

The term woolly hair, or tightly curled hair, refers to a structural anomaly of scalp hair, which can be partial or generalized. Generalized woolly hair variants are rare and can occur in isolation or in association with other cutaneous and extra-cutaneous abnormalities. Thus, it is important to dismiss in these patients the diagnosis of syndromes such as the Noonan syndrome and Cardiofaciocutaneous syndrome, which have high morbidity and mortality rates. We report the clinical case of a 7 year-old boy with generalized woolly hair and keratosis pilaris. After an evaluation of organs and systems, no alteration or characteristics associated with these syndromes were found.

Síndrome de rapp hodgkin: a propósito de un caso: Centro de Recuperación Nutricional "Dr. Pastor Oropeza" San Cristóbal Estado Táchira-Venezuela noviembre 2003 / Rapp-Hodgkin syndrome: a purpose of a case: Centro de Recuperación Nutricional Dr. Pastor Oropeza San Cristóbal stado Táchira-Venezuela november 2003

La displasia ectodérmica hereditaria (DEH), representa un grupo de disturbios caracterizados por aplasia o displasia de estructuras y tejidos derivados del ectodermo. Las estructuras generalmente afectadas incluyen el cabello, piel, uñas, dientes y diversas glándulas. Esta condición representa un disturbio raro y se estima su frecuencia de un caso a cada 10.000 ó 100.000 nacimientos. La detección de la DEH en recién nacidos y en los primeros años de la infancia puede ser tarea difícil, debido a pocos cabellos y pelos, así como la ausencia de dientes, son características muy comunes durante esos períodos. Después de los primeros años de vida el diagnóstico es realizado con mayor facilidad, basados en la historia clínica del paciente y el examen físico. Es importante resaltar que en muchas circunstancias la DEH puede presentar características semejantes o hasta estar asociada a otros síndromes, tales como a ectocractilia displasia ectodérmica (EEC), síndrome trico-rino-falangeral y enfermedad de Robinson. El tratamiento de la DEH es exitosa cuando se establece el diagnóstico en el período adecuado o sea en la infancia. Un control multidisciplinario, instituido en los primeros años de vida del paciente, puede minimizar las posibles complicaciones odontológicas y médicas.

Nevo de cabelo lanoso / Woolly hair nevus

O nevo de cabelo lanoso é condiçäo rara näo determinada geneticamente, caracterizada por cabelos muito encaracolados e que näo se agrupam em mechas, em uma ou mais áreas do couro cabeludo. Os autores apresentam o caso de menino de um ano de idade com várias áreas de cabelos muito encaracolados, características de nevo de cabelo lanoso, associado a nevus unius lateralis. Näo foram diagnosticadas outras alteraçöes ou malformaçöes sistêmicas. Fazem, ainda, breve discussäo de casos anteriormente relatados na literatura médica, enfatizando a necessidade de investigaçäo sistêmica nos casos associados ao nevo epidérmico

Moniletrix: comunicación de un caso y revisión de la literatura / Molinethrix: a case report and review of the literature

Femenino de 10 años de edad con dermatosis caracterizada por alopecia difusa, pelos cortos y pápulas foliculares, padecimiento que concidía con queratosis pilar. El tricograma mostró presencia de pelos moniliformes con nudosidades y zonas estrechas, hallazgo que fue confirmado con histología. Existieron antecedentes familiares hasta tres generaciones anteriores a la que pertenece el propósito. Se presenta una revisión del tema.

Hipoplasia cartílago-pelo: descripción de dos casos de origen mexicano / Cartilage-hair hypoplasia: two cases description of mexican origen

Se presentan dos niños mexicanos con hipoplasia cartílago-pelo y se describen sus particularidades clínicas destacando la rareza de este proceso.

Menkes' kinky hair syndrome

We herein describe a case of Menke's syndrome in a Jamaican infant. The diagnosis was confirmed by low serum copper and ceruloplasmin levels.