RESUMEN
Generalized hypertrichosis is a feature of several genetic disorders, and the nosology of these entities is still provisional. Recent studies have implicated chromosome 17q24.2-q24.3 microdeletion and the reciprocal microduplication in a very rare form of congenital generalized hypertrichosis terminalis (CGHT) with or without gingival hyperplasia. Here, we report on a 5-year-old Egyptian girl born to consanguineous parents. The girl presented with CGHT and gingival hyperplasia for whom we performed detailed clinical, pathological, and molecular studies. The girl had coarse facies characterized by bilateral epicanthic folds, thick and abundant eyelashes, a broad nose, full cheeks, and lips that constituted the distinctive facial features for this syndrome. Biopsy of the gingiva showed epithelial marked acanthosis and hyperkeratosis with hyperplastic thick collagen bundles and dense fibrosis in the underlying tissues. Array analysis indicated a 17q24.2-q24.3 chromosomal microdeletion. We validated this microdeletion by real-time quantitative PCR and confirmed a perfect co-segregation of the disease phenotype within the family. In summary, this study indicates that 17q24.2-q24.3 microdeletion caused CGHT with gingival hyperplasia and distinctive facies, which should be differentiated from the autosomal recessive type that lacks the distinctive facies.
Asunto(s)
Facies , Fibromatosis Gingival/diagnóstico , Fibromatosis Gingival/genética , Hipertricosis/diagnóstico , Hipertricosis/genética , Secuencia de Bases , Preescolar , Deleción Cromosómica , Cromosomas Humanos Par 17/genética , Consanguinidad , Análisis Mutacional de ADN , Femenino , Fibromatosis Gingival/patología , Genotipo , Humanos , Hipertricosis/patología , Datos de Secuencia Molecular , FenotipoRESUMEN
We describe a 2-year-old boy born to healthy, consanguineous parents. He had craniofacial asymmetry with left frontal bossing, midface hypoplasia, proptosis, and low-set ears. In addition, he had curly, light hair, and oval hypomelanotic patches in the abdomen, lower limbs and back and one hyperpigmented patch in the groin without acanthosis nigricans. Cranial three-dimensional CT scan showed right-coronal, sagittal, and lambdoid suture synostoses. His cranial MRI at 2-months of age showed left hemimegalencephaly, hypoplasia of corpus callosum, and an abnormal configuration of hippocampus. In spite of these cranial findings, he had mild developmental delay and his neurological examination showed symmetric strength, tone and reflexes. Apart from febrile seizures, there was no history of epilepsy. The proband developed asymmetric hydrocephalus at the age of 18 months that required third ventriculostomy. Post-operative cranial MRI showed Chiari I- like malformation and asymmetry of cerebral hemispheres but less dysplastic cerebral cortex. Mutation analysis of FGFR3 showed a c.749C > G, p.Pro250Arg substitution. To the best of our knowledge, these manifestations have not been reported in patients with Muenke syndrome.
Asunto(s)
Encéfalo/patología , Malformaciones del Desarrollo Cortical/patología , Trastornos de la Pigmentación/patología , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Preescolar , Craneosinostosis/genética , Craneosinostosis/patología , Análisis Mutacional de ADN , Humanos , Imagen por Resonancia Magnética , Masculino , Malformaciones del Desarrollo Cortical/genética , Mutación Missense/genética , Trastornos de la Pigmentación/genéticaRESUMEN
The designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of autosomal recessive disorders, comprising microcephaly, growth retardation, and a skeletal dysplasia. The different types of MOPD have been delineated on the basis of clinical, radiological, and genetic criteria. We describe two brothers, born to healthy, consanguineous parents, with intrauterine and postnatal growth retardation, microcephaly with abnormal gyral pattern and partial agenesis of corpus callosum, and skeletal anomalies reminiscent of those described in MOPD type I. This was confirmed by the identification of the homozygous g.55G > A mutation of RNU4ATAC encoding U4atac snRNA. The sibs had yellowish-gray hair, fair skin, and deficient retinal pigmentation. Skin biopsy showed abnormal melanin function but OCA genes were normal. The older sib had an intracranial hemorrhage at 1 week after birth, the younger developed chilblains-like lesions at the age 2½ years old but analysis of the SAMHD1 and TREX1 genes did not show any mutations. To the best of our knowledge, vasculopathy and pigmentary disorders have not been reported in MOPD I.
Asunto(s)
Enanismo/genética , Retardo del Crecimiento Fetal/genética , Microcefalia/genética , Mutación , Osteocondrodisplasias/genética , Trastornos de la Pigmentación/genética , Adolescente , Agenesia del Cuerpo Calloso/genética , Agenesia del Cuerpo Calloso/patología , Preescolar , Consanguinidad , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Enanismo/patología , Femenino , Retardo del Crecimiento Fetal/patología , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Microcefalia/patología , Osteocondrodisplasias/patología , Linaje , Examen Físico , Trastornos de la Pigmentación/patología , Embarazo , Tercer Trimestre del Embarazo , ARN Nuclear Pequeño/análisis , HermanosRESUMEN
Kabuki syndrome (KS) is extensively described in the literature and characterized by a typical facial gestalt in combination with postnatal short stature, hypotonia, joint laxity, developmental delay, persistent fetal fingertip pads, and an ever-growing group of congenital abnormalities. In this study, we focus on some ectodermal manifestations that we have observed. We studied seven patients who fulfilled the clinical criteria for KS and undertook a detailed clinical, dental, cytogenetic, and immunoglobulin assessments. In addition, microscopic hair examinations were performed on all patients and compared with matched control patients. All patients had receding of the anterior hair line, but five had evident sparse frontal scalp hair. They all showed peculiar similar microscopic hair abnormalities in the form of twisting of the hair shafts, irregularity of the diameter of the hair, and trichorrhexis nodosa. In addition, hypoplastic nails, café-au-lait patches, and missing upper lateral incisors were observed in 57.1%, 28.6%, and 14.3% of the patients, respectively. Variable orodental anomalies were seen in all the patients with an everted lower lip found in four patients (57.1%). This report provides further evidence that some cases of KS have ectodermal involvement.
Asunto(s)
Ectodermo/anomalías , Cabello/anomalías , Anomalías Múltiples , Manchas Café con Leche/epidemiología , Preescolar , Cara/anomalías , Femenino , Enfermedades Hematológicas , Humanos , Incidencia , Lactante , Masculino , Anomalías Dentarias/epidemiología , Enfermedades VestibularesRESUMEN
In this report, we describe two unrelated Egyptian male infants with limb malformations and constriction rings. The first case is developing normally but has severe limb anomalies, congenital constriction rings, scoliosis because of vertebral anomalies, a left accessory nipple, a small tumor-like swelling on his lower back with tiny skin tubular appendages, a hypoplastic scrotum, and an anchored penis. The second case is developmentally delayed with limb malformations, congenital constriction rings, a lumbar myelomeningeocele, hemangioma, and tiny tubular skin appendages on the back. The patient also had bilateral optic atrophy. The constellation of features in our patients cannot be fully explained by the amniotic disruption complex. The first patient may represent an additional case of the human homolog of the mouse disorganization mutant. The presence of bilateral optic atrophy in the second case, although without an absent septum pellucidum nor other brain anomalies resembles the infrequently reported disorder of septo-optic dysplasia with limb anomalies. Both cases were sporadic and could be caused by a new dominant mutation because of the high paternal age of case 1 and the history of paternal occupational exposure to heat for both fathers. We draw attention to the phenotypic overlap between the disorganization-like syndrome and septo-optic dysplasia with limb anomalies.