ABSTRACT
CASE DESCRIPTION: We report the case of a one-year-old girl who was diagnosed with Wiedemann-Steiner Syndrome based on the identification of a novel de novo frameshift mutation in the KMT2A gene by whole exome sequencing and supported by her clinical features. CLINICAL FINDINGS: KMT2A mutations cause Wiedemann-Steiner Syndrome, a very rare genetic disorder characterized by congenital hypertrichosis, short stature, intellectual disability, and distinct facial features. TREATMENT AND OUTCOME: Whole exome sequencing identified a novel frameshift variant: c. 4177dupA (p.Ile1393Asnfs * 14) in KMT2A; this change generates an alteration of the specific binding to non-methylated CpG motifs of the DNA to the protein. The genotype and phenotype of the patient were compared with those of earlier reported patients in the literature. CLINICAL RELEVANCE: In diseases with low frequency, it is necessary to establish a genotype-phenotype correlation that allows the establishment of therapeutic and follow-up goals. The phenotype comparation with other reported cases did not show differences attributable to sex or age among patients with Wiedemann-Steiner Syndrome. Whole exome sequencing allows identifying causality in conditions with high clinical and genetic heterogeneity like hypertrichosis.
DESCRIPCIÓN DEL CASO: Se reporta el caso de una paciente femenina de un año de edad, diagnosticada con Síndrome de Wiedemann-Steiner basado en la identificación de una nueva variante patogénica de novo de tipo frameshift en el gen KMT2A Mediante secuenciación de exoma usando el enfoque de trio, sumado a sus características clínicas. HALLAZGOS CLÍNICOS: las mutaciones en KMT2A causan el Síndrome de Wiedemann-Steiner, un desorden genético muy raro caracterizado por hipertricosis congénita, talla baja, retardo mental variable y fenotipo facial distintivo, los cuales se encuentran en la paciente reportada. RESULTADO: La Secuenciación de exoma completo encontró una variante de tipo frameshift: c.4177dupA (p. Ile1393Asnfs * 14) en KMT2A, este cambio a nivel génico genera una alteración de la unión específica a motivos CpG no metilados del DNA a la proteína. El genotipo y el fenotipo de la paciente fue comparado con los pacientes reportados previamente en la literatura. RELEVANCIA CLÍNICA: En enfermedades con baja frecuencia como la aquí reportada es necesario establecer correlaciones genotipo-fenotipo que permitan establecer planes terapéuticos y de seguimiento. El análisis realizado no evidenció diferencias atribuibles a sexo o edad entre los pacientes diagnosticados con Síndrome de Weidemann-Steiner. La secuenciación de exoma permitió identificar causalidad en este caso, cuya característica principal de hipertricosis se asocia con alta heterogeneidad clínica y genética.
Subject(s)
Abnormalities, Multiple/diagnosis , Histone-Lysine N-Methyltransferase/genetics , Hypertrichosis/congenital , Intellectual Disability/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Abnormalities, Multiple/genetics , Female , Genotype , Humans , Hypertrichosis/genetics , Infant , Mutation , Phenotype , SyndromeABSTRACT
Abstract Case Description: We report the case of a one-year-old girl who was diagnosed with Wiedemann-Steiner Syndrome based on the identification of a novel de novo frameshift mutation in the KMT2A gene by whole exome sequencing and supported by her clinical features. Clinical Findings: KMT2A mutations cause Wiedemann-Steiner Syndrome, a very rare genetic disorder characterized by congenital hypertrichosis, short stature, intellectual disability, and distinct facial features. Treatment and Outcome: Whole exome sequencing identified a novel frameshift variant: c. 4177dupA (p.Ile1393Asnfs * 14) in KMT2A; this change generates an alteration of the specific binding to non-methylated CpG motifs of the DNA to the protein. The genotype and phenotype of the patient were compared with those of earlier reported patients in the literature. Clinical Relevance: In diseases with low frequency, it is necessary to establish a genotype-phenotype correlation that allows the establishment of therapeutic and follow-up goals. The phenotype comparation with other reported cases did not show differences attributable to sex or age among patients with Wiedemann-Steiner Syndrome. Whole exome sequencing allows identifying causality in conditions with high clinical and genetic heterogeneity like hypertrichosis.
Resumen Descripción del caso: Se reporta el caso de una paciente femenina de un año de edad, diagnosticada con Síndrome de Wiedemann-Steiner basado en la identificación de una nueva variante patogénica de novo de tipo frameshift en el gen KMT2A Mediante secuenciación de exoma usando el enfoque de trio, sumado a sus características clínicas. Hallazgos clínicos: las mutaciones en KMT2A causan el Síndrome de Wiedemann-Steiner, un desorden genético muy raro caracterizado por hipertricosis congénita, talla baja, retardo mental variable y fenotipo facial distintivo, los cuales se encuentran en la paciente reportada. Resultado: La Secuenciación de exoma completo encontró una variante de tipo frameshift: c.4177dupA (p. Ile1393Asnfs * 14) en KMT2A, este cambio a nivel génico genera una alteración de la unión específica a motivos CpG no metilados del DNA a la proteína. El genotipo y el fenotipo de la paciente fue comparado con los pacientes reportados previamente en la literatura. Relevancia clínica: En enfermedades con baja frecuencia como la aquí reportada es necesario establecer correlaciones genotipo-fenotipo que permitan establecer planes terapéuticos y de seguimiento. El análisis realizado no evidenció diferencias atribuibles a sexo o edad entre los pacientes diagnosticados con Síndrome de Weidemann-Steiner. La secuenciación de exoma permitió identificar causalidad en este caso, cuya característica principal de hipertricosis se asocia con alta heterogeneidad clínica y genética.
Subject(s)
Female , Humans , Infant , Abnormalities, Multiple/diagnosis , Histone-Lysine N-Methyltransferase/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Hypertrichosis/congenital , Intellectual Disability/genetics , Phenotype , Syndrome , Abnormalities, Multiple/genetics , Genotype , Hypertrichosis/genetics , MutationABSTRACT
La hipertricosis cubital es un aumento localizado de la densidad, longitud y espesor del vello. Es una entidad benigna con muy escasos pacientes descritos en la literatura médica (alrededor de medio centenar). La mitad de los casos descritos asocian otros defectos o malformaciones, y la otra mitad son problemas puramente estéticos. La pubarquia precoz en niñas se define como el inicio del vello púbico antes de los 8 años de edad. Se presenta a una paciente de 6 años con la asociación no descrita previamente de hipertricosis cubital y pubarquia precoz.
Hypertrichosis cubiti is a localized increase in hair density, length and thickness. It is an uncommon and benign entity with very few patients described in the medical literature (more or less than half a hundred). Half of the described patients associate other defects or malformations and the other half are purely aesthetic cases. Early pubarche in girls is defined as the onset of pubic hair before 8 years of age. We present a six-year-old patient with the association not previously described of hypertrichosis cubiti and precocious pubarche.
Subject(s)
Humans , Female , Child , Puberty, Precocious/diagnosis , Growth Disorders/diagnosis , Hypertrichosis/congenital , Puberty, Precocious/pathology , Growth Disorders/pathology , Hypertrichosis/diagnosis , Hypertrichosis/pathologyABSTRACT
Hypertrichosis cubiti is a localized increase in hair density, length and thickness. It is an uncommon and benign entity with very few patients described in the medical literature (more or less than half a hundred). Half of the described patients associate other defects or malformations and the other half are purely aesthetic cases. Early pubarche in girls is defined as the onset of pubic hair before 8 years of age. We present a six-year-old patient with the association not previously described of hypertrichosis cubiti and precocious pubarche.
La hipertricosis cubital es un aumento localizado de la densidad, longitud y espesor del vello. Es una entidad benigna con muy escasos pacientes descritos en la literatura médica (alrededor de medio centenar). La mitad de los casos descritos asocian otros defectos o malformaciones, y la otra mitad son problemas puramente estéticos. La pubarquia precoz en niñas se define como el inicio del vello púbico antes de los 8 años de edad. Se presenta a una paciente de 6 años con la asociación no descrita previamente de hipertricosis cubital y pubarquia precoz.
Subject(s)
Growth Disorders/diagnosis , Hypertrichosis/congenital , Puberty, Precocious/diagnosis , Child , Female , Growth Disorders/pathology , Humans , Hypertrichosis/diagnosis , Hypertrichosis/pathology , Puberty, Precocious/pathologySubject(s)
Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/radiotherapy , Genetic Predisposition to Disease , Hypertrichosis/congenital , Low-Level Light Therapy/methods , Child , Diseases in Twins/diagnosis , Female , Follow-Up Studies , Genetic Diseases, X-Linked/diagnosis , Humans , Hypertrichosis/diagnosis , Hypertrichosis/genetics , Hypertrichosis/radiotherapy , Mexico , Pedigree , Severity of Illness Index , Twins, MonozygoticABSTRACT
We report the case of a girl with hypertrichosis lanuginosa congenita treated with diode laser depilation since the age of 9 months. The treatment was well tolerated, and neither general nor local anesthesia was needed. A reduction of approximately 80% of facial and body hair was noted, which improved her condition significantly.
Subject(s)
Hair Removal/methods , Hypertrichosis/congenital , Lasers, Semiconductor/therapeutic use , Female , Hair , Humans , Hypertrichosis/therapy , InfantABSTRACT
A 23-year-old woman presented to our hospital with 9 months history of progressive ataxia, visual loss since childhood due to retinitis pigmentosa and primary amenorrhea. On examination, there were also sparse scalp hair, very long and curled upwards eyelashes and short stature. Oliver-McFarlane syndrome was suspected. Brain MRI disclosed cerebellar atrophy and hyperintense signal in corticospinal tracts on FLAIR and T2-weighted images. Therefore, brain imaging must be thoroughly investigated in patients with suspected Oliver-McFarlane syndrome, in order to determinate whether cerebellar atrophy and hyperintense signal in corticospinal tracts are part of this neurological condition.
Subject(s)
Blepharoptosis/congenital , Blepharoptosis/pathology , Dwarfism/pathology , Hypertrichosis/congenital , Hypertrichosis/pathology , Intellectual Disability/pathology , Magnetic Resonance Imaging/methods , Pyramidal Tracts/pathology , Retinitis Pigmentosa/congenital , Retinitis Pigmentosa/pathology , Adult , Atrophy/pathology , Developmental Disabilities/pathology , Female , HumansABSTRACT
Congenital Hypertrichosis Lanugionsa is a rare autosomal dominant genetic disorder, with fewer than 50 cases reported in the literature. It is characterized by excessive lanugo hair, sparing only the mucous membranes, palms and soles. It may be associated with other organic abnormalities and should form part of the dermatologist's current knowledge. We discuss some aspects of the syndrome in question arising from the case report of a 2-year-old female patient, black, with classic clinical presentation, with no other associated congenital abnormalities.
Subject(s)
Hypertrichosis/congenital , Child, Preschool , Diagnosis, Differential , Female , Humans , Hypertrichosis/diagnosis , Hypertrichosis/genetics , Syndrome , Tooth AbnormalitiesABSTRACT
Congenital Hypertrichosis Lanugionsa is a rare autosomal dominant genetic disorder, with fewer than 50 cases reported in the literature. It is characterized by excessive lanugo hair, sparing only the mucous membranes, palms and soles. It may be associated with other organic abnormalities and should form part of the dermatologist's current knowledge. We discuss some aspects of the syndrome in question arising from the case report of a 2-year-old female patient, black, with classic clinical presentation, with no other associated congenital abnormalities.
A hipertricose Lanugionsa Congênita é uma desordem genética rara, autossômica dominante, com menos de 50 casos descritos na literatura. É caracterizada por pêlo lanugo excessivo, poupando apenas membranas mucosas, palmas e plantas. Pode estar associada a outras anormalidades orgânicas, devendo ser de conhecimento do dermatologista. Discutiremos aspectos da síndrome em questão a partir do relato de caso de uma paciente do sexo feminino, negra, 02 anos, com apresentação clínica clássica, sem outras anormalidades congênitas associadas.
Subject(s)
Child, Preschool , Female , Humans , Hypertrichosis/congenital , Diagnosis, Differential , Hypertrichosis/diagnosis , Hypertrichosis/genetics , Syndrome , Tooth AbnormalitiesABSTRACT
We report a large Mexican kindred with a variant form of congenital universal hypertrichosis that is inherited in an apparent X-linked recessive manner. In addition to the generalized hypertrichosis, the affected individuals have dental malformations and deafness. Males are more severely affected than females who exhibit only mild hypertrichosis, but not deafness or dental anomalies. Haplotype analysis in this pedigree revealed linkage to a 13-cM region on chromosome Xq24-q27.1 between markers GATA198A10 and DXS8106. Localization of the gene underlying this form of hypertrichosis is the initial step in identifying genes on the X chromosome that are involved in the control of hair growth and development.
Subject(s)
Chromosomes, Human, X , Deafness/genetics , Genetic Linkage , Hypertrichosis/congenital , Hypertrichosis/genetics , Tooth Abnormalities/genetics , Chromosome Mapping , DNA Mutational Analysis , Female , Genes, Recessive , Genotype , Haplotypes , Humans , Male , Mexico , Pedigree , PhenotypeABSTRACT
Hypertrichosis is hair growth that is abnormal for the age, sex, or race of an individual, or for a particular area of the body. Recognized forms of hypertrichosis are reviewed. Hirsutism, which is male-pattern hair growth in a female or child, is not included in this review. Hypertrichosis is categorized as congenital or acquired, and regional or generalized. Methods of managing hypertrichosis are also briefly reviewed
Subject(s)
Humans , Hypertrichosis/congenital , Hypertrichosis/etiology , Hypertrichosis/physiopathology , Hypertrichosis/therapy , SyndromeABSTRACT
Congenital generalized terminal hypertrichosis is a rare disease, especially when associated with gingival hyperplasia. Congenital hypertrichosis can be a clinical feature of several syndromes, so these patients must be studied by a multidisciplinary team that should include a dermatologist, geneticist, psychologist, odontologist, and an endocrinologist. We report a 7-year-old girl with congenital generalized hypertrichosis and gingival hyperplasia, and analyze the clinical approach, differential diagnosis, and treatment.
Subject(s)
Gingival Hyperplasia/congenital , Hypertrichosis/congenital , Child , Female , Gingival Hyperplasia/complications , Gingival Hyperplasia/surgery , Humans , Hypertrichosis/complications , Hypertrichosis/pathologyABSTRACT
Apresentamos uma paciente de 14 anos, de sexo feminino, portadora de um quadro de múltiplas anomalias congênitas: hipertelorismo, telecanto, macrostomia, agenesia da hélice em ambos os pavilhöes auriculares, pele grossa e redundante e hirsutismo severo, que corresponde ao 5º caso reportado de síndrome de Barber-Say. Esta paciente tem praticamente o mesmo fenótipo que a paciente descrita por Martínez Santana et al. (Am. J. Med. Genet. 47:20-23, 1992), incluindo o mesmo padräo dermatoglífico que näo havia sido descrito até entäo.
Subject(s)
Humans , Female , Adolescent , Abnormalities, Multiple/genetics , Hypertelorism , Macrostomia , Hypertrichosis/congenital , SyndromeABSTRACT
The hypertrichosis and osteochondrodysplasia syndrome is a rare entity with clinical findings including macrosomia at birth cardiomegaly. Autosomal recessive inheritance is presumed based on the report of two affected sibs born to healthy parents. Here we report on four new patients with their follow-up data, as well as on one of the four cases from the original report. Comparison of all eight cases indicates that they share 50% of clinical and radiological changes. This report contributes to the further delineation of this newly recognized syndrome.
Subject(s)
Abnormalities, Multiple/genetics , Cardiomegaly/congenital , Hypertrichosis/congenital , Osteochondrodysplasias/congenital , Adolescent , Cardiomegaly/diagnosis , Cardiomegaly/genetics , Child , Child, Preschool , Female , Humans , Hypertrichosis/diagnosis , Hypertrichosis/genetics , Male , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/diagnostic imaging , Osteochondrodysplasias/genetics , Phenotype , Radiography , Syndrome , X-RaysABSTRACT
El Síndrome de Waardenburg representa la forma más común de sordera congénita; es una condición pleitrópica, autosómica dominante, con penetrancia y expresividad variable. Se describen dos casos clínicos de Síndrome de Waardenburg tipo II. Las principales manifestaciones son la sordera sensorioneural congénita, alteraciones de la pigmentación pilosa y cutánea, puente nasal ancho, hipertricosis de las cejas, mandíbula cuadrada, encanecimiento prematuro y alteraciones neurológicas. Se revisan los criterios de diagnóstico de la enfermedad y los hallazgos asociados descritos de la literatura
Subject(s)
Humans , Male , Female , Adult , Deafness/congenital , Waardenburg Syndrome/physiopathology , Clinical Diagnosis , Eyebrows/abnormalities , Hair Color , Hypopigmentation/congenital , Hypertrichosis/congenital , Iris/abnormalities , Mandible/abnormalities , Nasal Cavity/abnormalities , Hearing Loss, Sensorineural/congenitalABSTRACT
Julia Pastrana (1834-1860) has gained immortality as one of the most extreme cases of generalized hypertrichosis upon record. When she was exhibited for money in the United States and Europe during the years 1855-1860, people thronged to see her, and she was several times described in the medical press of the day. After Julia Pastrana's death in childbirth, her corpse was embalmed in a very life-like manner, and exhibited all over Europe for several decades. Later, the mummy was believed to be lost, but in 1990 it was discovered at the Oslo Forensic Institute. Some writers have included Julia Pastrana among the cases of congenital hypertrichosis languinosa. However, a microscopic examination of hair samples from the mummy shows that her hairy growth is unmistakably terminal in character, and we propose that she instead was an example of congenital, generalized hypertrichosis terminalis with associated gingival hyperplasia. While many earlier writers have asserted that Julia Pastrana's dentition was abnormal, a radiographic examination of the mummy has shown that she had a complete permanent dentition.