Comprehensive review of the duplication 3q syndrome and report of a patient with Currarino syndrome and de novo duplication 3q26.32-q27.2.

Partial duplications of the long arm of chromosome 3, dup(3q), are a rare but well-described condition, sharing features of Cornelia de Lange syndrome. Around two thirds of cases are derived from unbalanced translocations, whereas pure dup(3q) have rarely been reported. Here, we provide an extensive review of the literature on dup(3q). This search revealed several patients with caudal malformations and anomalies, suggesting that caudal malformations or anomalies represent an inherent phenotypic feature of dup(3q). In this context, we report a patient with a pure de novo duplication 3q26.32-q27.2. The patient had the clinical diagnosis of Currarino syndrome (CS) (characterized by the triad of sacral anomalies, anorectal malformations and a presacral mass) and additional features, frequently detected in patients with a dup(3q). Mutations within the MNX1 gene were found to be causative in CS but no MNX1 mutation could be detected in our patient. Our comprehensive search for candidate genes located in the critical region of the duplication 3q syndrome, 3q26.3-q27, revealed a so far neglected phenotypic overlap of dup(3q) and the Pierpont syndrome, associated with a mutation of the TBL1XR1 gene on 3q26.32.

De novo 3q13.13q21.2 interstitial deletion and paternal 12p13.3 microdeletion in a fetus with dysplasia of the corpus callosum and ventriculomegaly: A case report.

Chromosome 3q syndrome is a well-known genetic condition caused by interstitial deletion in the long arm of chromosome 3. The phenotype of this syndrome is variable and the great variability in the extent of these deletions leads to a wide spectrum of clinical manifestations. Terminal 12p deletion represents one of the rarest subtelomeric imbalances; patients with distal monosomy 12p present different phenotypes ranging from muscular hypotonia to autism spectrum disorders. The present study reported a prenatal diagnosis of a male fetus presenting ultrasound evidence of corpus callosum dysplasia and ventriculomegaly showing a 3q13q21.2 deletion and a 12p13.33 microdeletion paternally inherited. Among several features previously attributed to the terminal deletion of 3q, corpus callosum dysplasia and ventriculomegaly have rarely been reported together. As the 12p13.33 microdeletion in the father was associated only with muscular hypotonia and joint laxity, the involvement of terminal 12p deletions in the clinical features of the fetus was not possible to verify during the prenatal period. The present case report may provide a reference for prenatal diagnosis and genetic counseling in patients who present 3q13q21.2 deletions and 12p13.33 microdeletion.

A new phenomenon of cochlear otosclerosis: an acquired or congenital disease? - A clinical report of cochlear otosclerosis.

BACKGROUND: No cochlear otosclerosis in infants with congenital bilateral SNHL has been reported. AIMS/OBJECTIVES: We report an infant male with bilateral cochlear otosclerosis, suggesting that cochlear otosclerosis may be a congenital disease and to further analyze the etiology of and genetic expression in congenital bilateral cochlear otosclerosis. We also describe the clinical characteristics and experience of patients with bilateral cochlear otosclerosis treated with cochlear implants (CIs). MATERIALS AND METHODS: Seven patients, including an infant, who were diagnosed with cochlear otosclerosis underwent CI surgery. Their medical records, audiological and radiological results, surgical procedures, and CI outcomes were collected and reviewed. RESULTS: The median age at hearing loss was 38 years, ranging from 0 to 47 years. The child had bilateral hearing loss at birth and received a CI at 1 year of age. He also had growth retardation and was diagnosed with 3q+/3p- syndrome. All patients (8 ears) had better postoperative auditory performance than that preoperatively. CONCLUSIONS AND SIGNIFICANCE: Although cochlear otosclerosis often starts at middle age and progresses slowly, it may be a congenital disease that is related to chromosome abnormality. This disease presents with SNHL or MHL, and treatment with a CI is beneficial.

A Pure 2-Mb 3q26.2 Duplication Proximal to the Critical Region of 3q Duplication Syndrome.

Partial duplication of chromosome 3q - dup(3q) - is a recognizable syndrome with dysmorphic facial features, microcephaly, digital anomalies, and genitourinary and cardiac defects, as well as growth retardation and developmental delay. Most cases of dup(3q) result from unbalanced translocations or inversions and are accompanied by additional chromosomal imbalances. Pure dup(3q) is rare, and only 31 cases have been reported so far. We report a new case of a girl with a pure 2-Mb duplication at 3q26.2 not encompassing the known critical region 3q26.3q27. After an extensive review, to the best of our knowledge, the case herein presented harbors the shortest 3q duplication of this region. The clinical phenotype of this patient resembles previously reported cases of pure dup(3q) syndrome, including intellectual disability, synophrys, a wide nasal bridge, dysmorphic ears, clinodactyly, and cardiac defects. We suggest that the 3q26.2 duplication is a candidate copy number alteration explaining our patient's clinical phenotype.

A Rare Combination of Functional Disomy Xp, Deletion Xq13.2-q28 Spanning the XIST Gene, and Duplication 3q25.33-q29 in a Female with der(X)t(X;3)(q13.2;q25.33).

We report a 19-year-old female patient with a history of short stature, primary ovarian insufficiency, sensorineural hearing loss, sacral teratoma, neurogenic bladder, and intellectual disability with underlying mosaicism for der(X)t(X;3)(q13.2;q25.33), a ring X chromosome, and monosomy X. Derivative X chromosomes from unbalanced X-autosomal translocations are preferentially silenced by the XIST gene (Xq13.2) located within the X-inactivation center. The unbalanced X-autosomal translocation in our case resulted in loss of the XIST gene thus precluding the inactivation of the derivative X chromosome. As a result, clinical features of functional disomy Xp, Turner's syndrome, and duplication 3q syndrome were observed. Importantly, indications of the derivative X chromosome were revealed by microarray analysis following an initial diagnosis of Turner's syndrome made by conventional cytogenetic studies approximately 18 months earlier. This case demonstrates the importance of utilizing microarray analysis as a first-line test in patients with clinical features beyond the scope of a well-defined genetic syndrome.