Trisomy 1q41-qter and monosomy 3p26.3-pter in a family with a translocation (1;3): further delineation of the syndromes.

BACKGROUND: Trisomy 1q and monosomy 3p deriving from a t(1;3) is an infrequent event. The clinical characteristics of trisomy 1q41-qter have been described but there is not a delineation of the syndrome. The 3p25.3-pter monosomy syndrome (MIM 613792) characteristics include low birth weight, microcephaly, psychomotor and growth retardation and abnormal facies. CASE PRESENTATION: A 2 years 8 months Mexican mestizo male patient was evaluated due to a trisomy 1q and monosomy 3p derived from a familial t(1;3)(q41;q26.3). Four female carriers of the balanced translocation and one relative that may have been similarly affected as the proband were identified. The implicated chromosomal regions were defined by microarray analysis, the patient had a trisomy 1q41-qter of 30.3 Mb in extension comprising about 240 protein coding genes and a monosomy 3p26.3-pter of 1.7 Mb including only the genes CNTN6 (MIM 607220) and CHL1 (MIM 607416), which have been implicated in dendrite development. Their contribution to the phenotype, regarding the definition of trisomy 1q41-qter and monosomy 3p26.3-pter syndromes are discussed. CONCLUSION: We propose that a trisomy 1q41-qter syndrome should be considered in particular when the following characteristics are present: postnatal growth delay, macrocephaly, wide fontanelle, triangular facies, frontal bossing, thick eye brows, down slanting palpebral fissures, hypertelorism, flat nasal bridge, hypoplasic nostrils, long filtrum, high palate, microretrognathia, ear abnormalities, neural abnormalities (in particular ventricular dilatation), psychomotor developmental delay and mental retardation. Our patient showed most of these clinical characteristics with exception of macrocephaly, possibly due to a compensatory effect by haploinsufficiency of the two genes lost from 3p. The identification of carriers has important implications for genetic counseling as the risk of a new born with either a der(3) or der(1) resulting from an adjacent-1 segregation is of 25% for each of them, as the products of adjacent-2 or 3:1 segregations are not expected to be viable.

Pure trisomy 2p syndrome in two siblings with an unbalanced translocation and minimal terminal 12q monosomy characterized by high-density microarray.

Pure partial trisomy 2p patients have rarely been reported. Oligonucleotide array analysis has proved to be important for examining 2p rearrangements to delineate the involved segment and to rule out additional imbalances modifying the phenotype. Here, we report 2 siblings with an unbalanced translocation that led to a partial trisomy 2p (p22.3pter) and a terminal deletion of 12q (q24.33qter). This finding was characterized by the molecular karyotyping of both siblings. The 12q loss spanned approximately 300 kb and did not yield clinical features in our patients. The trisomic region in the short arm of chromosome 2 spanned 32.8 Mb and yielded phenotypic features of pure distal 2p trisomy, notably facial anomalies, growth failure, and psychomotor delay. The clinical features of our patients help to delineate the phenotype of the pure trisomy 2p syndrome. Patient 2 also showed a horseshoe kidney which is a previously unrecognized defect associated with this syndrome.

El papel de la genética en la restricción del crecimiento intrauterino / The role of genetics in fetal growth restriction

Se define como restricción del crecimiento intrauterino (RCIU) a la alteración en el crecimiento fetal que determina un peso por debajo de la percentila 10 para la edad gestacional. Las causas genéticas de RCIU pueden dividirse en: cromosómicas, alteraciones de la epigenética o impronta y síndromes génicos. Se presenta el caso de una paciente con RCIU referida por sospecha de displasia ósea, en la que se descartó disfunción vascular placentaria por ultrasonido prenatal, infecciones, patología materna y displasias óseas por estudio radiológico normal. Se realizó cariotipo en el cordón umbilical y en tres diferentes sitios de la placenta por la posibilidad de un mosaico placentario, obteniéndose un resultado normal. Al nacimiento presentó peso y talla por debajo de la percentila 3, cráneo dolicocéfalo con frontal prominente, fontanela anterior amplia, cara pequeña, triangular con mentón en punta y clinodactilia bilateral. A los dos meses de edad se observó asimetría de extremidades inferiores y se refirió reflujo gastroesofágico. Con base en los criterios clínicos y resultados obtenidos se realizó el diagnóstico de síndrome de Silver-Russell.

Intrauterine growth restriction (IUGR) is an alteration in fetal development in which the fetal weight is below the 10th percentile for gestational age. The genetic causes of IUGR can be classified as: chromosomal, epigenetic and other imprinting disorders and monogenic syndromes. We report a patient with IUGR referred to our hospital with the prenatal diagnosis of achondroplasia. Vascular malfunction of the placentae, maternal pathology, and skeletal dysplasia were discarded. A karyotype in umbilical cord and in three different placental spots was performed, with a normal result in all of them, ruling out placentae mosaicism. At birth, the weight and height were below the 3th percentile. Physical examination showed: dolicocephaly, frontal prominence, large fontanels, small and triangular face, pointed chin and incurved bilateral fifth fingers. Two months later a lower limb asymmetry was noticed and gastroesophageal reflux was referred. With these clinical abnormalities and the studies performed the diagnosis of Silver-Russell syndrome was established.