Terminal deletion 11q in thrree children: narrowing the critical region for the 11q Jacobsen Syndrome phenotype

DEL REY G; CASALI B.; GUTIERREZ M; ARMANDO R.; LAUDICINA A.; GARCIÁ ESTRANGA P; MARTINO G.; BOYWITT A.; FERNANDEZ MC; DE BELLIS R.,; VILLEGAS MF.; ARBERAS C.,

Congreso; ? XXIV Sociedad Latinoamericana de Endocrinología Pediátrica. XV Sociedad Mexicana de Endocrinología Pediátric; 2014

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

Terminal deletion 11q in three children: narrowing the critical region for the 11qJacobsen syndrome phenotype. Background: Jacobsen syndrome is caused by partial deletion of the long arm of chromosome 11. Its incidence is 1/100,000 births with a female/male ratio of 2:1. Mainly features include pre- and postnatal growth retardation, psychomotor deficit and trombocitopenia. Characteristic facial dysmorphism such as skull deformities, hypertelorism, ptosis, coloboma, downslanting palpebral fissures, epicanthal folds, broad nasal bridge, short nose, v-shaped mouth, small ears and low set posteriorly rotated ears. Malformations of the heart, kidney, genitalia, and central nervous system are also present. Most of the patients have short stature, and some have growth hormone deficiency or central or primary hypothyroidism. The size of the deletion ranges from 7 to 20 Mb proximal or telomeric to 11q23.3. In 85% of cases the deletion is de novo and in the other15% it is the result of an unbalanced segregation from familial balanced translocation. 25% of the children died before the age of 2, mainly due to  and thrombocytopenia complications. It is proposed that a differential survival depending on the sex of the patient. The published cases show a wide range of phenotypic variability related either to differences in the size of the deletion or different ages of the patients. Methods: Patient 1 and 2: two siblings. At physical examination P1 a boy, age: 2.1 yrs, height: 85cm (10thPc); HC: 50.5 cm (0/+2 SD). P2: a girl, age: 1.1 yrs; height: 75 cm (50thPc); HC: 50 cm (0/+2 SD). Common findings included: narrow protruding forehead, hypertelorism, ptosis, strabismus, broad root, and short upturned tip of the nose, longest marked columella, rotated ears, long philtrum, v-shaped mouth and thin upper lip. Seizure and maturation delay. P2 died ofheart disease at age 15. Her brother presents at 19 a deep mental retardation, bicuspid aorta and frequent bleeding episodes. Patient 3: Full term female baby Asian origin. Height 40cm (<3rdPc); HC 32cm (-2.85/0 SD). 3rd trimester US showed: IUGR, small kidneys, ambiguous genitalia, oligoamnios. Mechanical ventilation was required immediately after birth. Physical exam showed broad and bombe front, flat face, short palpebral fissures, low-set ears with prominent antihelixand helix folding, clitoral hypertrophy. Patient presented intraventricular hemorrhage Grade I and moderate premature retinopathy. Ductus, PFO, and severe pulmonary hypertension. She died at 3 months of age by cardiac defect. Results: Karyotypes P1 and P2: partial deletion 11q from 11q24.1-qter and partial duplication 13q from 13q22.1-qter resulting from a maternal translocation 46,XX,t(11;13)(q24.1;q22.1). FISH analysis with a telomeric 11q probe confirmed a proximal deletion to 11qter. Karyotype P3: 46,XX,der(11)t(11;16)(q25; q22) resulted from a balanced paternal translocation. Discussion: P1 and P2 presented typical phenotypic characteristic of JBS due to monosomy 11qter. P3 showed a subtle 11q deletion from 11q25-qter and a duplication 16q22-qter, such as the clinical signs were explained mainly by the latter. Given thepresence of hemorrhage and thrombocytopenia a positional effect could affect FLI1 gene mapped in 11q24.3. Conclusion: The description of these three patients with different parental translocation and the delineation of their chromosomal rearrangements could help define the critical region in 11q24.1 chromosome for the typical abnormalities of JBS