Faciocardiorenal syndrome: a wide clinical spectrum?

Faciocardiorenal syndrome (FCRS), also named Eastman-Bixler syndrome, is an apparent autosomal recessive entity, characterized by endocardial fibroelastosis, unusual facial appearance, renal defects and mental retardation. We report a 7 months male patient, with the diagnosis of endocardial fibroelastosis, an abnormal facial appearance (arched eyebrows, broad nasal root, long philtrum and microretrognathia) and psychomotor delay. Associated anomalies were: plagiocephaly, broad halluces, nail hypoplasia, cryptorchidism, diastasis recti, and adducted thumbs. Focal seizures in the mouth were also observed. The radiographs revealed advanced bone age and metaphyseal widening of femur and tibia. FCRS has an unknown etiology with only three reported cases so far (since 1977). We report a patient with the main features of FCRS but without the renal component, suggesting that this entity can present a wide clinical spectrum. Based on these findings and on the few previously reported cases with a highly variable phenotype when compared with the original report, we suggest that FCRS should be further clinical delineated according to the following leading anomalies: endocardial fibroelastosis, unusual facial appearance and mental retardation, in order to find more cases that allow a wider clinical description and the identification of the genetic defect(s).

Wide clinical spectrum in Zimmermann-Laband syndrome.

Gingival fibromatosis can be present as an isolated form or be part of a genetic disease. The Zimmermann-Laband syndrome (ZLS) is a rare disorder inherited as an autosomal dominant fashion, clinically characterized by gingival fibromatosis, bulbous soft nose, thick floppy ears, nail dysplasia, joint hyperextensibility, hepatosplenomegaly, skeletal anomalies and occasional mental retardation. We studied a girl aged five years with clinical and radiological features of the ZLS, additionally she presented deafness not previously described in the ZLS, as only partial hearing loss was reported in some patients. The father presented some facial features suggestive of ZLS, nevertheless he did not have gingival fibromatosis or hypertrichosis. We suggest that this case supports that ZLS can be part a contiguous genes syndrome or be consequence ofa gene mutation with wide variable expression. The present report supports that ZLS has a wide clinical spectrum.

Duplication 5q and deletion 9p due to a t(5;9)(q34;p23) in 2 cousins with features of Hunter-McAlpine syndrome and hypothyroidism.

We report on 2 similarly affected cousins with a compound imbalance resulting from a familial t(5;9)(q34;p23) and entailing both an ∼17-Mb 5q terminal duplication and an ∼12-Mb 9p terminal deletion as determined by G-banding, subtelomere FISH, and aCGH. The proband's karyotype was 46,XX,der(9)t(5;9)(q34;p23)mat.ish der(9)t(5;9)(q34;p23)(9pter-,5qter+).arr 5q34q35(163,328,000-180,629,000)×3, 9p24p23(194,000-12,664,000)×1. Her cousin had the same unbalanced karyotype inherited from his father. The clinical phenotype mainly consists of a distinct craniofacial dysmorphism featuring microcephaly, flat facies, down slanting palpebral fissures, small flat nose, long philtrum, and small mouth with thin upper lip. Additional remarkable findings were craniosynostosis of several sutures, craniolacunia and preaxial polydactyly in the proband and hypothyroidism in both subjects. The observed clinical constellation generally fits the phenotypic spectrum of the 5q distal duplication syndrome (known also as Hunter-McAlpine syndrome), except for the thyroid insufficiency which can likely be ascribed to the concurrent 9p deletion, as at least 4 other 9pter monosomic patients without chromosome 5 involvement had this hormonal disorder. The present observation further confirms the etiology of the HMS phenotype from gain of the 5q35→qter region, expands the clinical pictures of partial trisomy 5q and monosomy 9p, and provides a comprehensive list of 160 patients with 5q distal duplication.

A teenager with a t(X;17)(q22;q25) and ovarian failure.

BACKGROUND: The effects of a balanced X; Autosome translocation [t(X;A)] on the fertility of carrier females led to the definition of the Xq13-->q27 region as critical for ovarian function and reproductive lifespan. We describe here a teenager with ovarian failure likely due to a balanced t(X;17)(q22;q25). CASE: The 16 year-old patient presented with secondary amenorrhea. She exhibited height of 164 cm, slender habitus, and sexual development Tanner 2. METHODS: Hormonal determinations, GTG- and RBG-banded karyotypes, fluorescence in situ hybridization, and human androgen receptor assay. RESULTS: FSH of 141 mIU/ml and LH of 46 mIU/ml); karyotype 46,X,t(X;17)(q22;q25)[30].ish der(X)t(X;1 7)(17qsubt el+); skewed inactivation of the normal X which was the maternal one as shown by the HUMARA assay. The maternal chromosomes were 46,XX; the father was unavailable. CONCLUSIONS: The patient's (X;17) translocation likely accounts for her ovarian failure via an epigenetic downregulation of ovary expressed 17q25 genes relocated next to the Xq21 POF Critical Region 1 and related to ovarian development and function. Her otherwise inconspicuous phenotype agrees with the preferential inactivation of the normal X-chromosome that preserves the gene homeostasis in women with a balanced t(X;A). Finally, the normal maternal karyotype along with the HUMARA results and the sterility of males carrying a t(X;A) strongly suggests that this t(X;17) was a paternal de novo mutation.