Two unrelated cases of single maxillary central incisor with 7q terminal deletion

Two unrelated cases of single maxillary central incisor (SM-CI) with 7q terminal deletion of the same breakpoint at 7q36.1 were described. They had mental retardation, microcephaly, hypotelorism, short stature, and normal levels of plasma growth hormone. One case had bilateral caudal ectopic kidneys, double renal pelves, and dilated ureters. The other had bilateral hydroureteronephrosis. The present cases suggest that 7q terminal deletion is one of the causes of SMCI.     

Clinical phenotype and molecular characterization of 6q terminal deletion syndrome: Five new cases

Mental retardation, facial dysmorphisms, seizures, and brain abnormalities are features of 6q terminal deletions. We have ascertained five patients with 6q subtelomere deletions (four de novo, one as a result of an unbalanced translocation) and determined the size of the deletion ranging from 3 to 13 Mb. Our patients showed a recognizable phenotype including mental retardation, characteristic facial appearance, and a distinctive clinico-neuroradiological picture. Focal epilepsy with consistent electroencephalographic features and with certain brain anomalies on neuroimaging studies should suggest 6q terminal deletion. The awareness of the distinctive clinical picture will help in the diagnosis of this chromosomal abnormality.     

1q24 deletion syndrome. Two cases and new insights into genotype‐phenotype correlations

1q24q25 deletions cause a distinctive phenotype including proportionate short stature, microcephaly, brachydactyly, dysmorphic facial features and intellectual disability. We present a mother and son who have a 672 kb microdeletion at 1q24q25. They have the typical skeletal features previously described but do not have any associated intellectual disability. We compare the genes within our patients' deletion to those in the deletions of previously reported cases. This indicates two genes that may be implicated in the intellectual disability usually associated with this deletion syndrome; PIGC and C1orf105. In addition, our cases provide supporting evidence to recent published work suggesting that the skeletal features may be linked to the microRNAs miR199 and miR214, encoded within intron 14 of the Dynamin‐3 gene.     

Patient with terminal duplication 3q and terminal deletion 5q: comparison with the 3q duplication syndrome and distal 5q deletion syndrome

Partial duplication of chromosome 3q is a well-described condition of multiple congenital anomalies and developmental delay that resembles the Brachmann-de Lange syndrome. Similarly, an emerging phenotype of a distal 5q deletion syndrome has recently been described. The combination of both chromosome abnormalities has not been previously described. We report on a child with both a de novo duplication of distal 3q (q27 --> qter) and terminal deletion of 5q (q35.2 --> qter). The patient had facial anomalies, hypoplastic toenails, lymphedema of the dorsum of the feet, type I Chiari malformation, a seizure disorder, and moderate developmental delays. The phenotype is compared and contrasted to the few reports of patients with similar terminal 3q duplications and 5q deletions. Our patient did not have the characteristic phenotype of the 3q duplication syndrome, suggesting that the chromosome region responsible for this phenotype is more proximal than the terminal 3q27 region. In addition, comparison with three other reported cases of terminal 5q35 deletions suggests a possible association of terminal 5q deletions with central nervous system (CNS) structural abnormalities.     

Bladder exstrophy and extreme genital anomaly in a patient with pure terminal 1q deletion: expansion of phenotypic spectrum

We describe a 5 2/12 years old male patient with a de novo deletion 1q43q44 of approximately 10.4 Mb in size. The boy presented with the classic features of chromosome 1q43q44 deletion syndrome including growth and psychomotor retardation, microcephaly, distinct facial features and various midline defects as agenesis of corpus callosum, cardiac and urogenital anomalies. Fronto-parietal simplified gyral pattern was an additional neuroimaging finding. The urogenital anomalies in our patient were remarkable in form of bladder exstrophy and severe hypogenitalism with a marked hypoplastic scrotum, small sized retractile testis and absent phallus. To the best of our knowledge, bladder exstrophy and absence phallus have not been previously reported in terminal deletion 1q43q44 syndrome. This report provides further evidence of phenotype-genotype correlation and expands the phenotypic spectrum of midline defects described with this syndrome.     

Clinical phenotype associated with terminal 2q37 deletion

Three children with deletions of the terminal portion of the long arm of chomosome 2 [del (2) (q37)] are described and their clinical findings compared to published cases of 2q terminal deletions. Common clinical findings include development delay, macrocephaly, frontal bossing, depressed nasal bridge and cardiac anomaly. Hypotonia and repetitive behavior are also seen during different times of development. The facial characteristics of children with 2q terminal deletions are not uniform, but development delay is a constant finding. Chromosomal analysis of such children using high resolution banding may uncover the diagnosis of a small chromosomal deletion.     

Chromosome 1q terminal deletion resulting fromde novo translocation with an acrocentric chromosome

Summary Distal deletion of chromosome 1q has been reported in nearly 30 patients, all being associated with a deletion ranging from the 1q42 or q43 band to 1qter region. Here, we describe a girl with 1q terminal deletion resulting from an unbalancedde novo translocation t(1;D or G)(q44; p11), as revealed by the presence of a satellited feature and an NOR-stained region at the tip of 1q. We suggest that most of the phenotypic abnormalities seen in patients with 1q distal deletion are attributable to the monosomy for band 1q44.     

Cerebellar and posterior fossa malformations in patients with autism‐associated chromosome 22q13 terminal deletion

The 22q13.3 deletion causes a neurodevelopmental syndrome, also known as Phelan‐McDermid syndrome (MIM #606232), characterized by developmental delay and severe delay or absence of expressive speech. Two patients with hemizygous chromosome 22q13.3 telomeric deletion were referred to us when brain‐imaging studies revealed cerebellar vermis hypoplasia (CBVH). To determine whether developmental abnormalities of the cerebellum are a consistent feature of the 22q13.3 deletion syndrome, we examined brain‐imaging studies for 10 unrelated subjects with 22q13 terminal deletion. In seven cases where the availability of DNA and array technology allowed, we mapped deletion boundaries using comparative intensity analysis with single nucleotide polymorphism (SNP) microarrays. Approximate deletion boundaries for three additional cases were derived from clinical or published molecular data. We also examined brain‐imaging studies for a patient with an intragenic SHANK3 mutation. We report the first brain‐imaging data showing that some patients with 22q13 deletions have severe posterior CBVH, and one individual with a SHANK3 mutation has a normal cerebellum. This genotype–phenotype study suggests that the 22q13 deletion phenotype includes abnormal posterior fossa structures that are unlikely to be attributed to SHANK3 disruption. Other genes in the region, including PLXNB2 and MAPK8IP2, display brain expression patterns and mouse mutant phenotypes critical for proper cerebellar development. Future studies of these genes may elucidate their relationship to 22q13.3 deletion phenotypes. © 2012 Wiley Periodicals, Inc.     

The 11q terminal deletion disorder: a prospective study of 110 cases

We performed a prospective study of 110 patients (75 not previously published) with the 11q terminal deletion disorder (previously called Jacobsen syndrome), diagnosed by karyotype. All the patients have multiple dysmorphic features. Nearly all the patients (94%) have Paris-Trousseau syndrome characterized by thrombocytopenia and platelet dysfunction. In total, 56% of the patients have serious congenital heart defects. Cognitive function ranged from normal intelligence to moderate mental retardation. Nearly half of the patients have mild mental retardation with a characteristic neuropsychiatric profile demonstrating near normal receptive language ability, but mild to moderate impairment in expressive language. Ophthalmologic, gastrointestinal, and genitourinary problems were common, as were gross and fine motor delays. Infections of the upper respiratory system were common, but no life-threatening infections were reported. We include a molecular analysis of the deletion breakpoints in 65 patients, from which genetic "critical regions" for 14 clinical phenotypes are defined, as well as for the neuropsychiatric profiles. Based on these findings, we provide a comprehensive set of recommendations for the clinical management of patients with the 11q terminal deletion disorder.     

A new case of deletion 1q42 syndrome

We report a 1 8/12-year-old male with a de novo deletion of 1q42. The case is compared with 23 others from the literature. The clinical manifestations of our patient correspond with the phenotype of previous reports.     

Caudal deficiency sequence in 7q terminal deletion

We describe a male infant with signs of caudal deficiency sequence. In addition, he showed growth retardation, microcephaly, prominent forehead, bulbous nose tip, large dysplastic ears, hypospadia, partial sacral agenesis, and neurologic bladder dysfunction. Chromosome examination showed a terminal 7q deletion 46,XY,del(7)(pter----q32:). Four previous reported cases of 7q terminal deletion and signs of caudal deficiency are reviewed. Chromosome aberrations may, at least in some cases, be responsible for developmental defects.     

Two cases of interstitial deletion 1p.

We report two cases of interstitial deletion of the short arm of chromosome 1. The first was a 10 year old boy whose karyotype was 46,XY,del(1) (p22.1p31.2); the second was a 6 month old boy with a chromosome complement of 46,XY,del(1) (p22.3p31.3). A number of the malformations observed were common to both cases. There has been one previously reported case with the same breakpoints as our case 1 and a phenotype that was strikingly similar.     

A 1-Mb critical region in six patients with 9q34.3 terminal deletion syndrome

Patients with 9q34.3 terminal deletion usually show a clinically recognizable phenotype characterized by specific facial features (microcephaly, flat face, arched eyebrows, hypertelorism, short nose, anteverted nostrils, carp mouth and protruding tongue) in combination with severe mental retardation, hypotonia, and other anomalies. We analyzed six unrelated patients with a various 9q34.3 terminal deletion. While having different-sized 9q34.3 deletions, all of these patients shared several distinctive anomalies. These anomalies are likely to arise from a commonly deleted region at distal 9q34.3. Fluorescence in situ hybridization (FISH) analysis using a dozen BAC clones mapped at the 9q34.13-q34.3 region defined the shortest region of deletion overlap (SRO) as a 1-Mb segment proximal to 9qter containing eight known genes. Possible candidate genes delineating specific phenotypes of the 9q34.3 terminal deletion syndrome are discussed.     

Prenatal diagnosis of mosaicism for 11q terminal deletion

The phenotype of 11q terminal deletion also known as Jacobsen syndrome is a clinically well known entity whose diagnosis in infancy and childhood is based on clinical examination, hematological and cytogenetic findings. Hematological features in Jacobsen syndrome are very similar to those reported in Paris–Trousseau syndrome (PTS) which is also associated with11q terminal deletion. Karyotype analysis shows a variable terminal deletion from 11q23 sub-band extending to the telomere. Most often in patients with Jacobsen syndrome, this chromosomal deletion is present in all metaphases. We report on the identification of a distal 11q deletion in mosaic (20% of deleted cells) in a fetus ascertained after amniocentesis for maternal serum screening test indicative for Down syndrome. The present case is the third prenatal diagnosis of a mosaic for a distal 11q deletion with the lowest mosaicism rate. The 2D-ultrasound examination and cord blood hematological studies were useful to estimate the prognosis at term, considering the contribution of the mosaicism rate to the phenotypic variability in Jacobsen syndrome. The identification of mosaicism for distal 11q deletion is a very rare event in prenatal diagnosis. This case illustrates the complexity in genetic counselling for prenatally ascertained partial monosomy 11qter in mosaic.