Silvia Castillo T

Síndrome de Williams: estudio clínico, citogenético, neurofisiológico y neuroanatómico

Background: Williams syndrome (WS) is a genetically based disorder caused by deletion of elastin and contiguous genes on chromosome 7q11.23. This syndrome is characterized by multiorganic involvement with dysmorphic facial features and a distinctive cognitive profile. It is an interesting model for elucidation of relationships between brain, cognition and genes. Patients have a visual-spatial cognition impaired with relative strengths in social and language abilities. Aim: To report clinical, cytogenetic, neurophysiological and neuroanatomic features in 44 patients referred as WS. Patients and methods: Forty four patients, aged 2 to 17 years, with the clinical diagnosis of Williams syndrome were studied with fluorescence in situ hybridization (FISH). In three cases, electrophysiological and neuroimaging studies were performed. Result: The deletion was confirmed in 23 patients. In three patients with neurophysiological studies, event related potentials suggested a cognitive difficulty in detecting and processing visual stimuli. Magnetic resonance imaging showed normal brain morphology. SPECT showed hypoperfusion of the right frontal lobe and bilateral anterior cingulum hyperperfusion. Conclusions: There are functional alterations in the brains of patients with Williams, which may be related to the cognitive deficits (Rev Med Chile 2002; 130: 631-37)

Prevalencia al nacimiento de aberraciones cromosómicas en el Hospital Clínico de la Universidad de Chile: Período 1990-2001

Background: A cytogenetical study should be performed to every newborn with malformations. If a chromosomal aberration is found, parents must be studied to give an adequate genetic advise. Aim: To study the frequency of chromosomal aberrations in newborns with malformations. Patients and methods: In the Clinical Hospital of the University of Chile all malformations in newborns are registered, as part of the Collaborative Latin American Study of Congenital Malformations (ECLAMC). The frequency of chromosomal aberrations, determined by cytogenetical studies, was determined in newborns with malformations. Results: In the study period, there were 32,214 births. Of these, 2,268 live newborns and 43 stillbirths had malformations. Ninety nine children with malformations had chromosomal aberrations (4.3%). Trisomy 21 was the most common aberration with a rate of 23/10,000 births, followed by trisomy 18 with a rate of 4/10,000 and trisomy 18 with a rate of 1.2/10,000. Ninety four percent of these children were born alive and 16.1% died before discharge from the hospital. The masculinity indexes for Down syndrome and for trisomy 18 were 0.38 and 0.61 respectively. Conclusions: A higher frequency of female gender for trisomy 21 and male gender for trisomy 18 has not been reported previously (Rev Med Chile 2003; 131: 651-658)

Frecuencia de los defectos de cierre del tubo neural en las maternidades públicas de Santiago durante el año 1999

Background: Fortification of wheat flour with folic acid in Chile, started in January 2000. This fortification should decrease the incidence of neural tube defects. Aim: To study the incidence of neural tube defects among Chilean newborns, during 1999. Material and methods: The records of all newborns and stillbirths with a birth weight over 500 g from 9 public maternity hospitals in Santiago in 1999, were reviewed. All neural tube defects, associated or not to other malformations were taken into account. Results: During the study period, 59.627 newborns and 455 stillbirths were analyzed. The global incidence of neural tube defects was 1.56 per 1.000 born (57% women, 42% men and 1% ambiguous sex). Spina bifida was the most frequent neural tube defect found. Conclusion: These baseline data will be useful to assess the impact of folic acid fortification of wheat flour. (Rev Med Chile 2001; 129: 277-84).

Displasia Ectodérmica hipohidrótica, caso clínico y revisión de la literatura

La displasia ectodermica hipohidrotica (DEH) es un trastorno genetico que se caracteriza por hipohidrosis, hipotricosis e hipodoncia. Comunmente afecta a varones con una herencia recesiva ligada al X, aunque existen otras formas con herencia autosomica dominante y recesiva. Los pacientes afectados pueden presentar intolerancia al calor, fiebre, hipertermia grave e incluso muerte subita. Objetivo: Presentan el caso clinico de un paciente portador de DEH, y actualizar el conocimiento de la etiologia y medidas terapeuticas de esta patologia. Caso clinico: Se reporta el caso de una nina de 7 anos de edad, que presenta escaso vello, alteraciones dentarias, amastia y escasa sudoracion, compatible con una DEH y una probable herencia autosomica recesiva. Se comenta su evolucion y manejo clinico, junto a aspectos embriologicos, geneticos, diagnosticos y el consejo genetico de esta enfermedad

Estudio genético de una familia chilena con tres fenotipos dentales diferentes

Background: Congenital dental anomalies can affect up to 25% of the population. Aim: To report the genetic study of a family with dental anomalies. Material and methods: We studied a Chilean family presenting with three independent dental phenotypes: third molar agenesis, supernumerary teeth, and dentinal dysplasia type I. We searched for mutations in candidate genes proposed for tooth agenesis and supernumerary teeth: IRF6, FGFR1, MSX1, MSX2, PAX9, PRDM16 and TGFA. We also studied DSPP as a candidate gene for dentinal dysplasia type I. Results: We did not find mutations in FGFR1, MSX2, PAX9, PRDM16, or TGFA. We found a MSX1 mutation (G16D) in both affected and unaffected family members. Also, we found a genetic variation not described before in IRF6 in the dentinal dysplasia type I case. Conclusions: Further investigation is necessary to evaluate if these variants are functional in nature. Finally, we are reporting a mutation in DSPP in an asymptomatic 2-year-old child, which illustrates the ethical pitfalls of interpreting molecular data for genetic counseling of young and/or

SÍNDROME DE MORQUIO (MUCOPOLISACARIDOSIS TIPO IV) Y EMBARAZO

RESUMENSe presenta el caso de una paciente embarazada, portadora de Sindrome de Morquio (Muco-polisacaridosis tipo IV), que evoluciona con polihidroamnios y disnea. Se comenta el manejo y resoluciondel caso.PALABRAS CLAVES: Sindrome de Morquio, mucopolisacaridosis tipo IV, embarazoSUMMARYWe report the case of a pregnant women with Morquio syndrome (Mucopolysaccharidosis type IV), thatpresented polihydramnios and dyspnea. The management and resolution of the case are commented.KEY WORDS: Morquio syndrome, mucopolysaccharidosis type IV, pregnancy Casos Clinicos *Trabajo presentado por Dr. Hugo Salinas el 6 de septiembre de 2005 en Sesion Ordinaria de la Sociedad Chilena deObstetricia y Ginecologia. vivos (2). No existe evidencia en la literatura sobreel embarazo en estas pacientes, motivo por elcual comunicamos nuestra experiencia en el ma-nejo de este caso.CASO CLINICOPaciente de 21 anos de edad, trasladada des-de el Hospital Clinico Regional de Valdivia al Hos-pital Clinico de la Universidad de Chile el 10 demayo de 2005, portadora de una MPS tipo IV yque cursa con un embarazo de 20 semanas. Estapatologia fue diagnosticada a los 8 anos de edaden 1993, en Puerto Montt, mediante estudio demucopolisacaridos en orina. Tenia estudio de co-lumna cervical; la TAC revelo inestabilidad cervicalINTRODUCCIONLa mucopolisacaridosis tipo IV fue descrita en1929 por Morquio en Montevideo, Uruguay. Sinembargo, Brailsford en Inglaterra caracterizaba deforma simultanea esta patologia, por lo que estecuadro se denomina Sindrome de Morquio-Brailsford (1). Este sindrome forma parte de lasmucopolisacaridosis (MPS), enfermedades meta-bolicas hereditarias causadas por el deficit deenzimas lisosomicas que producen acumulacionde mucopolisacaridos (llamados actualmente glico-saminoglicanos) en los tejidos. La MPS tipo IV secaracteriza por ser de herencia autosomica rece-siva, afectar de igual manera a hombres y muje-res, con una incidencia de 1 en 200.000 nacidos

Síndrome de Coffin-Siris: casos clínicos y revisión de la literatura

Presentamos los casos clinicos de 2 pacientes de sexo femenino de 10 y 5 anos de edad, que tenian retraso del crecimiento de inicio posnatal, retardo mental, cabello ralo, hirsutismo corporal, facies tosca, cejas pobladas, nariz ancha, filtrum largo, boca grande, micrognatia, escoliosis, braquidactilia de predominio distal, pulpejos prominentes e hipoplasia ungueal del quinto dedo bilateral. El cariograma en sangre fue normal 46XX. Considerndo las caracteristicas clinicas de ambas pacientes se realizo el diagnostico de sindrome de Coffin-Siris, enfermedad genetica de la que existen menos de 100 casos publicados. La forma de herencia de este sindrome, al parecer autosomica dominante, aun se encuentra en discusion. El sindrome de Coffin-Siris debe ser considerado en el diagnostico diferencial del retardo mental asociado a rasgos toscos

ENDOMETRIOSIS FAMILIAR: REPORTE DE UNA FAMILIA CON HERENCIA MENDELIANA

RESUMENLa endometriosis es una causa importante de dolor pelvico e infertilidad en las mujeres premeno-pausicas. Aunque poco se conoce sobre su etiopatogenia, se considera como un trastorno multifactorialdonde se conjugan elementos endocrinologicos, inmunologicos, ambientales y geneticos. El estudio degenes candidatos no ha sido exitoso en la ubicacion de genes de susceptibilidad. Se reporta una familiacon tres hermanas afectadas de endometriosis, se comenta su evolucion y posibles implicancias geneticas.PALABRAS CLAVE: Endometriosis, geneticaSUMMARYEndometriosis is an important cause of pelvic pain and infertility in the premenopausal women. Althoughfew is known about its etiology, it is recognized as a multifactorial disorder where endocrine, immunologic,environmental and genetic factors, join together. The study of candidate genes has failed in the location ofgenes of susceptibility. We report a family where three sisters are affected by endometriosis; their evolutionand possible genetic implications are commented.KEY WORDS: Endometriosis, genetic

Hernia diafragmática congénita y malformaciones asociadas.

La hernia diafragmatica congenita (HDC) continua siendo me patologia que pone en peligro la vida a pesar de los adelantos en su manejo. Las malformaciones congenitas asociadas resultan ser uno de los factores mas importantes que contribuyen a elevar los tasas de mortalidad en estos pacientes. En este trabajo presentamos nuestra experiencia con relacion a esta anomalia, la cual forma parte del Estudio Colaborativo Latinoamericano de Malformaciones Congenitos (ECLAMC), enfocado principalmente en lo asociacion de la HDC con otras malformaciones Congenitas, y revise mas los aspectos relacionadcs con el patron de herencia involucrado en los casos familiares de HDC. En este estudio encontramos que las malformaciones mayo res, especialmente las cardiacas, y un bajo peso al nacer confieren un mal pronostico a los recien nacidos con HDC.

Alteraciones cromosómicas en niños referidos para estudio citogenética

From year 1981 throughout 1 993 we have performed 1 473 caryotipes in patients aged 0 to 15 years. Referencediagnosis were Downs syndrome [30,8%), multiple malformations (19,1%), psychomoto r retardation (10,5%), Turnerssyndrome 18%), abnormal sexual developmeni (7,6%), short stature (7,1%), speech development disturbances (2%) andmiscelaneous syndromes (14,9%). The efficiency of the investigation for chromosomal abnormalities varied accordinglyto clinical diagnosis: Downs syndrome (94.0%), multiple malformations (24.8%), psychomolor retardation (13.4%),Turner s syndrome [55.6%), abnormal sexual development (T 3.4%), speech disturbances [10.0%) and other syndromes[9.1 %). Chromosomal study allows confirmation of clinically suspected cases of chromosomal anomalies or -if normal- itpromotes ihe search of non chromosomal etiologies in apparently similar phenotypes, and it represents an importantcontribution to genetic counsel for affected families.(Keywords: Chromosomes, human, abnormalities, cytogenetics, kariotyping.)