Diagnóstico clínico de síndrome de Levy-Hollister familiar / Clinical diagnosis of familial Levy-Hollister syndrome

El síndrome lácrimo-aurículo-dento-digital (síndrome LADD o también conocido como síndrome de Levy-Hollister) es un defecto autosómico dominante con expresividad variable. Este síndrome se caracteriza por la asociación de displasias en diversos órganos y sistemas que afectan a las estructuras craneofaciales, incluyendo glándulas lagrimales y salivales, dientes, oído interno y externo y el esqueleto óseo. Presentamos este síndrome inusual y desconocido (es el primer caso en nuestro estado del que existen solamente cerca de 100 casos descritos, distribuidos en pocas familias) en referencia a un adolescente de 17 años ingresado en la Unidad de Cuidados Intensivos Pediátricos por otro motivo y que tras la exploración física se llega a un diagnóstico clínico en toda la rama familiar

Lacrimo-auriculo-dento-digital syndrome (LADD syndrome), also known as Levy-Hollister syndrome, is an autosomal dominant defect with variability on phenotypical expression. This syndrome is characterised by the association of dysplasia in various organs and systems that affect craniofacial structures, including lachrymal and salivary glands, teeth, internal and external ear, and the bone skeleton. We present this unusual and almost unknown syndrome (the first case in our state, with only about 100 cases described in the world, distributed in a few families) in a teenager of 17 years admitted to PICU for another reason. After the physical examination, a clinical diagnosis was made in the entire family branch

[Clinical diagnosis of familial Levy-Hollister syndrome]. / Diagnóstico clínico de síndrome de Levy-Hollister familiar.

Lacrimo-auriculo-dento-digital syndrome (LADD syndrome), also known as Levy-Hollister syndrome, is an autosomal dominant defect with variability on phenotypical expression. This syndrome is characterised by the association of dysplasia in various organs and systems that affect craniofacial structures, including lachrymal and salivary glands, teeth, internal and external ear, and the bone skeleton. We present this unusual and almost unknown syndrome (the first case in our state, with only about 100 cases described in the world, distributed in a few families) in a teenager of 17 years admitted to PICU for another reason. After the physical examination, a clinical diagnosis was made in the entire family branch.

Síndrome de Crouzon: a propósito de 2 casos. Entidades craneoestenóticas alélicas de los genes FGFR / Presentation of two cases of Crouzon syndrome: allelic cranio-stenotic conditions of FGFR genes

Introducción: La craneosinostosis consiste en una fusión patológica precoz de una o varias suturas craneales. El 20% de los casos corresponde a formas sindrómicas con patrones hereditarios mendelianos, mientras que el 80% restante a formas no sindrómicas, pero con transmisión hereditaria en el 10-14% de los casos. A propósito de 2 pacientes con síndrome de Crouzon, se revisan los aspectos clínicos y genéticos. Pacientes y métodos: Paciente 1: niña de 35 días con macrocefalia progresiva, abombamiento de la fontanela, proptosis ocular, hipertelorismo y estrabismo divergente. Rx de cráneo con sinostosis de la sutura sagital. Fue intervenida quirúrgicamente a los 3 y 8 meses por desarrollo de pansinostosis. Paciente 2: niño de 3 años 8 meses con cefaleas de tipo migrañoso de un año de evolución. Presentaba acantosis nigricans. Rx de cráneo y TC craneal con impresiones digitales y fondo de ojo con discreto borramiento papilar. Tras 18 meses apareció edema de papila y en la TC craneal se detectó pansinostosis, requiriendo intervención quirúrgica. Resultados: Hemos presentado un paciente con síndrome de Crouzon clásico (paciente 1) y otro con acantosis nigricans (paciente 2), diagnosticándose por su particular fenotipo clínico. Conclusiones: Dada la amplia diversidad de formas alélicas en los genes FGFR que cursan con craneosinostosis, conociéndose hasta 10 entidades, realizamos una revisión de las mismas. En las formas sindrómicas, como nuestros 2 casos, conviene detallar al máximo los signos clínicos pues pueden orientar el diagnóstico, y el estudio molecular permitirá en ocasiones confirmarlo y ofrecer asesoramiento genético a las familias(AU)

Introduction: Craniosynostosis is an abnormal and premature fusion of any cranial suture. Twenty per cent of them involve any specific syndrome with Mendelian transmission; the other 80% are "non syndromic", although but 10-14% of them are genetically transmitted. Using the experience of two patients with Crouzon syndrome, a clinical and genetic review is performed. Patients and methods: Patient 1: girl of 35 days of age with progressive macrocephaly, protrusion of fontanel, ocular proptosis, hypertelorism and divergent strabismus. Cranial RX with sagittal synostosis. Surgical operation was performed with 3 months and 8 months of age due to development of pansynostosis. Patient 2: boy of 3 years 8 months of age with headaches of migrainous type of one year onset. He had acanthosis nigricans. Cranial RX and cerebral CT with evident digital markings and fundus of eye with undefined papillary limits, but 18 month later oedematous papilla were evident and pansynostosis was detected, so surgery was performed. Results: We present a patient with classical Crouzon syndrome (patient 1) and another with acanthosis nigricans (patient 2), both diagnosed by the description of characteristic clinical features. Conclusions: Ten craniosynostotic clinical forms are currently known as allelic variations of the FGFR genes, and as such have reviewed them. As in our two cases, in syndromic types is very important the accurate study of the phenotype to orientate the diagnosis, although the molecular study will confirm it in many patients and genetic counselling offered(AU)

[Presentation of two cases of Crouzon syndrome: allelic cranio-stenotic conditions of FGFR genes]. / Síndrome de Crouzon: a propósito de 2 casos. Entidades craneoestenóticas alélicas de los genes FGFR.

INTRODUCTION: Craniosynostosis is an abnormal and premature fusion of any cranial suture. Twenty per cent of them involve any specific syndrome with Mendelian transmission; the other 80% are "non syndromic", although but 10-14% of them are genetically transmitted. Using the experience of two patients with Crouzon syndrome, a clinical and genetic review is performed. PATIENTS AND METHODS: Patient 1: girl of 35 days of age with progressive macrocephaly, protrusion of fontanel, ocular proptosis, hypertelorism and divergent strabismus. Cranial RX with sagittal synostosis. Surgical operation was performed with 3 months and 8 months of age due to development of pansynostosis. Patient 2: boy of 3 years 8 months of age with headaches of migrainous type of one year onset. He had acanthosis nigricans. Cranial RX and cerebral CT with evident digital markings and fundus of eye with undefined papillary limits, but 18 month later oedematous papilla were evident and pansynostosis was detected, so surgery was performed. RESULTS: We present a patient with classical Crouzon syndrome (patient 1) and another with acanthosis nigricans (patient 2), both diagnosed by the description of characteristic clinical features. CONCLUSIONS: Ten craniosynostotic clinical forms are currently known as allelic variations of the FGFR genes, and as such have reviewed them. As in our two cases, in syndromic types is very important the accurate study of the phenotype to orientate the diagnosis, although the molecular study will confirm it in many patients and genetic counselling offered.

Deleción intersticial del brazo largo del cromosoma 4(4q12q21.1): comunicación de un nuevo caso / Intersticial deletion of the long arm of chromosome 4(4q12-q21.1): report oa a new case

Se comunica un nuevo caso de deleción proximal del brazo largo del cromosoma 4 de novo, en un niño de 3 años de edad con rasgos fenotípicos compatibles con un síndrome de Waardemburg tipo II. Presentaba mechón de pelo blanco frontal, hipoacusia neurosensorial bilateral, desplazamiento lateral de cantos internos, heterocromía de iris, fisura velopalatina, lesiones hipocrómicas en tronco, hipotonía axial, extremidades cortas, deformidades de cuerpos vertebrales, retraso mental y ponderoestatural, reflujo gastroesofágico, síndrome de malabsorción, panhipopituitarismo, comunicación interauricular tipo ostium secundum, hipermetropía (11 dioptrías) y dificultad para la deglución. El cariotipo de alta resolución realizado en células de sangre periférica y piel hipo/hiperpigmentada puso de manifiesto una deleción intersticial en el brazo largo del cromosoma 4 (4q12-q21.1). El estudio mutacional del gen MITF (Waardenburg II) fue normal. Se revisan los casos similares descritos anteriormente en la bibliografía y se resalta que la asociación retraso mental y ponderoestatural en niños con rasgos fenotípicos que recuerdan al síndrome de Waardenburg o al piebaldismo aislado deben alertar sobre posibles deleciones en la estructura del brazo largo del cromosoma 4(AU)

We report a new case of a de novo interstitial deletion of the long arm of chromosome 4, in a three-year-old boy, with phenotypic features compatible with Waardenburg syndrome type II. Clinical examination disclosed the following abnormalities: white forelock, sensorineural hearing loss, hypertelorism, irisheterochromia, cleft palate, hypotonia, depigmented areas in trunk, short limbs and deformities in vertebral bodies, mental retardation and developmental delay. Further studies showed gastroesophageal reflux, malabsorption syndrome, panhypopituitarism, atrial septal defect, hypermetropia (11 diopters) and swallowing difficulties. Chromosome analysis of peripheral blood cells and hypopigmented and hyperpigmented skin cells showed an interstitial deletion of the long arm of chromosome 4 (4q12-q21.1). The results of the mutational study of the MITF gene (Waardenburg II) were normal. Genetic studies of the parentsal so produced normal results. We have reviewed similar cases previously published in the literature, and we stress the fact that the association of growth failure and mental retardation in children with a phenotype resembling piebald trait or Waardenburg syndrome should alert us to the possibility of deletions in the structure of the long arm of chromosome 4(AU)

[Septo-optic dysplasia]. / Displasia septóptica.

INTRODUCTION: Septo optic syndrome, described by De Morsier in 1956, consists in the hypoplasia of one or both optic nerves, mid line brain malformations and hypothalamohypophysial dysfunction, which is inconstant. It is an infrequent, but treatable, cause of hepatic and neurological damage, and it is important to obtain an early diagnosis and to begin hormone replacement therapy. CASE REPORT: We report the clinical case of a female baby who was diagnosed early on as suffering from septo?optic dysplasia, after discovery of the existence of cholestatic jaundice. In our case the three components of the syndrome were present: hypothalamohypophysial dysfunction, bilateral hypoplasia of the optic nerves and brain malformations with dysplasia of the transparent septum. All this gives rise to complex clinical features and the predominance of hypernatraemic dehydration secondary to insipid diabetes, nystagmus and serious psychomotor retardation. Our patient died, as in other cases reported in the literature, from an episode of sudden death. DISCUSSION: Despite the importance of an early diagnosis of this disorder, it is usually late. Most children who present hypopituitarism traits in the neonatal period are not diagnosed at that time, with the subsequent risk of death or brain damage. Some clinical findings, which appear early on and can provide clues which aid us to reach a diagnosis, are the appearance of episodes of hypoglycaemia in the neonatal period, the existence of micropenis and cryptorchidism with hypoplasic testes, jaundice or the appearance of clinical manifestations of insipid diabetes. Later on nystagmus and neurological symptoms may appear. The final diagnosis is performed through the use of neuroimaging techniques (CT or MRI) and hormonal studies.

Displasia septóptica / Septo-optic dysplasia

Introducción. El síndrome septóptico, descrito por De Morsier en 1956, consiste en la hipoplasia de uno o ambos nervios ópticos, malformaciones cerebrales de línea media y disfunción hipotalamohipofisaria, la cual es inconstante. Es una causa poco frecuente, pero tratable, de daño hepático y neurológico, y es de gran importancia su diagnóstico precoz e instauración de tratamiento hormonal substitutivo. Caso clínico. Presentamos el caso clínico de una lactante que se diagnosticó precozmente de displasia septoóptica, a partir de la existencia de ictericia colestática. En nuestro caso se presentan los tres componentes del síndrome: disfunción hipotalamohipofisaria, hipoplasia bilateral de nervios ópticos y malformaciones cerebrales con displasia del septum pellucidum. Todo ello da lugar a una florida clínica, y predomina la deshidratación hipernatrémica secundaria a diabetes insípida, nistagmo y grave retraso psicomotor. Nuestra paciente falleció, como otros casos descritos en la bibliografía, por un episodio de muerte súbita. Discusión. Pese a la importancia del diagnóstico precoz de esta entidad, éste suele ser tardío. La mayoría de niños que presentan rasgos de hipopituitarismo en el período neonatal no se diagnostican en ese momento, con el consecuente riesgo de muerte o daño cerebral. Algunos hallazgos clínicos, que aparecen tempranamente y que pueden darnos la pista para llegar al diagnóstico, son la aparición de episodios de hipoglucemia en el período neonatal, la existencia de micropene y criptorquidia con testes hipoplásicos, ictericia o aparición de manifestaciones clínicas de diabetes insípida. Más adelante, pueden aparecer nistagmo y síntomas neurológicos. El diagnóstico definitivo se realiza mediante técnicas de neuroimagen (TAC o RM) y estudios hormonales (AU)

Síndrome de Beckwith-Wiedemann. Aportación de cinco casos y revisión de la literatura / Beckwith-Wiedemann syndrome: a report

Presentamos nuestra experiencia con el síndrome de Beckwith-Wiedemann (SBW), aportando cinco casos, cuyo diagnóstico y seguimiento se llevó a cabo en nuestro centro y que se registraron desde el año 1987 hasta 1998. Todos ellos son hijos de padres sanos no consanguíneos. Presentan un desarrollo psicomotor normal, y la edad media de seguimiento ha sido de 5,2 años (rango: 20 meses-10 años). Todos ellos, menos uno, cumplen al menos 3 criterios mayores: patología onfalica, macroglosia, hipoglucemia neonatal y gigantismo pre y/o posnatal y alguno de los diferentes criterios menores descritos en este síndrome. Los cinco pacientes sobreviven en la actualidad. El caso 5 es una forma incompleta de la enfermedad, pero que presenta la característica del desarrollo de un tumor de Wilms a lo largo de su evolución (AU)

Clinical and immunological spectrum of partial DiGeorge syndrome.

We present four cases of DiGeorge syndrome diagnosed at our center. Onset occurred during the neonatal period and was associated with severe congenital heart disease. In case 1, the patient had heart disease and absence of thymus. Total T-lymphocytes were 34%; total T4-lymphocytes were 27%. Stimulation test with phytohemagglutinin (PHA), concanavalin A (conA) and pokeweed mitogen were negative. Microdeletion was found in the chromosome 22q11 region. The second case involved heart disease, microstomia, round and rotated ears and branchial cyst. Total T-lymphocytes were 38% and total T4-lymphocytes 27%. Thymus was absent. Microdeletion in the chromosome 22q11 region. Case 3 showed heart disease, renal malformation, absence of thymus and parathyroid gland. The patient died 5 days postsurgery. Microdeletion was seen at chromosome 22q11. In the fourth case there was heart disease, microretrognathia, hypertelorism, short neck, absence of thymus and parathyroid glands. Total T-lymphocytes were 22%, total T4-lymphocytes 15%, and total T lymphocytes for pokeweed mitogen were negative. Microdeletion was found at chromosome 22q11. At the age of 13 days the patient died. The cases were recorded during a 2-year period, between 1997 and 1998. The prevalence of DiGeorge syndrome in the number of admissions for congenital heart disease among the neonates at our hospital was 3.14%. Presentation in the form of repeated infections is rare, since most cases of DiGeorge syndrome are partial, and functional cellular immunity is preserved.