Deletion 2q36.2q36.3 with multiple renal cysts and severe mental retardation

Interstitial 2q36 deletion is a rare event. We report on a patient with a de novo del(2)(q36.2q36.3) interstitial deletion of the long arm of chromosome 2 diagnosed by classical banding. The phenotype comprised facial dysmorphism, enlarged kidneys with multiple renal cysts, abnormal minora labia, asymmetric lower limbs with dysplastic patella, and severe mental retardation. By physical mapping, using array-comparative genomic hybridisation (CGH) confirmed by Fluorescent In Situ Hybridisation (FISH), the breakpoints of the deletion were mapped and the size of the deletions was measured: 5.61 ± 0.19 Mb. A skin biopsy was analysed using electronic microscopy showing an alteration of the structure and organisation of the dermal and peri-neuronal basement membrane. The relation between the phenotype and the deletion of both COL4A4 and COL4A3 genes, located in 2q36.3 loci, as well as the disruption of TRIP12 were discussed.     

5q12.1 deletion: delineation of a phenotype including mental retardation and ocular defects

Array‐CGH enables the detection of submicroscopic chromosomal deletions and duplications and leads to an accurate delineation of the imbalances, raising the possibility of genotype to phenotype and mapping minimal critical regions associated with particular patterns of clinical features. We report here on four patients sharing common clinical features (psychomotor retardation, coarse facies and ocular anomalies), with proximal 5q deletions identified by oligo array‐CGH. The deletions range from 5.75 to 17.26‐Mb in size and occurred de novo. A common 2.63‐Mb region between the deletions described here can be defined in 5q12.1 (59,390,122–62,021,754 bp from 5pter, hg18) and includes 12 genes. Among them, KIF2A, which encodes a kinesin superfamily protein, is a particularly interesting candidate for the phenotype, as it suppresses the growth of axonal collateral branches and is involved in normal brain development. Ocular defects, albeit unspecific, seem to be common in the 5q12.1 deletion. Identification of additional cases of deletions involving the 5q12.1 region will allow more accurate genotype–phenotype correlations. © 2011 Wiley‐Liss, Inc.     

Delineation of PIGV mutation spectrum and associated phenotypes in hyperphosphatasia with mental retardation syndrome

Three different genes of the glycosylphosphatidylinositol anchor synthesis pathway, PIGV, PIGO, and PGAP2, have recently been implicated in hyperphosphatasia-mental retardation syndrome (HPMRS), also known as Mabry syndrome, a rare autosomal recessive form of intellectual disability. The aim of this study was to delineate the PIGV mutation spectrum as well as the associated phenotypic spectrum in a cohort of 16 individuals diagnosed with HPMRS on the basis of intellectual disability and elevated serum alkaline phosphate as minimal diagnostic criteria. All PIGV exons and intronic boundaries were sequenced in 16 individuals. Biallelic PIGV mutations were identified in 8 of 16 unrelated families with HPMRS. The most frequent mutation detected in about 80% of affected families including the cases reported here is the c.1022C>A PIGV mutation, which was found in both the homozygous as well as the heterozygous state. Four further mutations found in this study (c. 176T>G, c.53G>A, c.905T>C, and c.1405C>T) are novel. Our findings in the largest reported cohort to date significantly extend the range of reported manifestations associated with PIGV mutations and demonstrate that the severe end of the clinical spectrum presents as a multiple congenital malformation syndrome with a high frequency of Hirschsprung disease, vesicoureteral, and renal anomalies as well as anorectal malformations. PIGV mutations are the major cause of HPMRS, which displays a broad clinical variability regarding associated malformations and growth patterns. Severe developmental delays, particular facial anomalies, brachytelephalangy, and hyperphosphatasia are consistently found in PIGV-positive individuals.     

Deletion of 7q34-q36.2 in two siblings with mental retardation, language delay, primary amenorrhea, and dysmorphic features

We describe a chromosome rearrangement, ins(7;13)(q32q34;q32), which segregates in a three generation family, giving rise to three individuals with an unbalanced rearrangement. Two of the individuals, a sister and a brother, were investigated further in this study. They had minor facial dysmorphism and neuropsychiatric disorders including mental retardation, language delay and epilepsy. The sister had primary amenorrhea. Array CGH revealed a 12.2?Mb deletion at 7q34-q36.2 including more than 60 genes where CNTNAP2 and NOBOX are of special interest. Comparison of the clinical and cytogenetic findings of our patients with previously reported patients, supports that haploinsuffiency of CNTNAP2 can result in language delay and/or autism spectrum disorder. Furthermore, we report on the second women with a deletion involving NOBOX who is affected by primary amenorrhea.     

Alport syndrome,mental retardation,midface hypoplasia,and elliptocytosis: a new X linked contiguous gene deletion syndrome?

We describe a family with four members, a mother, two sons, and a daughter, who show clinical features consistent with X linked Alport syndrome. The two males presented with additional features including mental retardation, dysmorphic facies with marked midface hypoplasia, and elliptocytosis. The elliptocytosis was not associated with any detectable abnormalities in red cell membrane proteins; red cell membrane stability and rigidity was normal on ektacytometry. Molecular characterisation suggests a submicroscopic X chromosome deletion encompassing the entire COL4A5 gene. We propose that the additional abnormalities found in the affected males of this family are attributable to deletion or disruption of X linked recessive genes adjacent to the COL4A5 gene and that this constellation of findings may represent a new X linked contiguous gene deletion syndrome.     

Ectro-amelia syndrome associated with an interstitial deletion of 7q

We describe a premature male infant with an interstitial deletion of 7q [46,XY,del(7) (pter----q21.3::q31.3----qter]. Manifestations include absence of lower limbs, unilateral ectrodactyly, facial anomalies, gingival hyperplasia, feeding problems, and atrial septal defect. Chromosome 7 deletions of the q21.3----q31.3 region are reviewed with emphasis on limb anomalies.     

Cat-like cry and mental retardation owing to 7q interstitial deletion (7q22 leads to 7q32).

A patient with mental retardation and mild facial dysmorphism had a karyotype which was considered to be normal before the availability of chromosomal banding techniques. She had a history of a cat-like cry and severe feeding problems during infancy. At the age of 9, she was still found to have initial aphonia on trying to initiate sounds. Repeat chromosome analysis with G banding showed an interstitial deletion of the long arm of chromosome 7.     

Interstitial 2.2 Mb deletion at 9q34 in a patient with mental retardation but without classical features of the 9q subtelomeric deletion syndrome

In a female patient with mild mental retardation an interstitial subtelomeric 9q34.3 deletion was identified by a multiplex ligation-dependent probe amplification (MLPA) based screen for subtelomeric abnormalities. Further characterization of the deletion by high-resolution tiling path array-based comparative genomic hybridization (array CGH) revealed a size of 2.2 Mb. The woman lacked the typical 9qter deletion phenotype characteristics, which is inline with the finding that both Eu-HMTase1 (EHMT) genes were present. However, she presented with mild mental retardation, some mild facial dysmorphisms and aplasia cutis. This is another example of an interstitial subtelomeric deletion, which underscores that further characterizing the precise nature of the deletion is of clinical importance. Moreover, it confirms the importance of the Eu-HMTase1 gene as the major causative factor of the classical 9qter syndrome phenotype.     

Hyperphosphatasia with mental retardation,brachytelephalangy, and a distinct facial gestalt: Delineation of a recognizable syndrome

The association of mental retardation and persistent hyperphosphatasia has been described in rare instances. Because of parental consanguinity and sib recurrences autosomal recessive inheritance has been proposed. We report three sibs with a syndrome consisting of severe mental retardation, considerably elevated serum levels of alkaline phosphatase, hypoplastic terminal phalanges, and distinct facial features. Clinically and radiologically, shortness of distal phalanges could be demonstrated in all of them. Their particular facial appearance led us to two earlier reported familial cases with convincing clinical similarities. We suggest a specific clinical entity within the spectrum of patients with mental retardation and hyperphosphatasia, which is in particular characterized by a recognizable facial gestalt and brachytelephalangy.     

Interstitial deletion of 5q33.3q35.1 in a girl with mild mental retardation

Constitutional interstitial deletions of 5q are uncommon. The corresponding phenotype is not well defined. But severe mental retardation seems to be a consistent manifestation. We describe a 4-year-old girl with a de novo deletion of 5q33.3q35.1 presenting only with mild psychomotor delay, minor facial anomalies, and seizures.     

Unknown syndrome: nasal hypoplasia, sparse hair, truncal obesity, genital hypoplasia, and severe mental retardation.

A 4 year old girl is described with severe mental retardation, peculiar face with nasal hypoplasia, sparse hair, genital hypoplasia, truncal obesity, puffy hands, and small feet with complete cutaneous syndactyly of the second and third toes.     

Bilateral ulna hypoplasia,club feet,and mental retardation: A new mesomelic syndrome

We report on 2 sibs with a previously unreported type of mesomelia of the upper limbs due to ulnar hypoplasia. Prenatal diagnosis was made by ultrasound during one pregnancy and an affected fetus was confirmed. This family documents a previously unreported autosomal recessive syndrome. © 1995 Wiley-Liss, Inc.     

Genitopatellar syndrome: a new condition comprising absent patellae, scrotal hypoplasia, renal anomalies, facial dysmorphism, and mental retardation

We report on the association of absent patellae, genital and renal anomalies, dysmorphic features, and mental retardation in seven children (six boys and one girl) belonging to five unrelated families. Flexion deformities of the knees and hips with club feet and absent patellae were consistently observed and scrotal hypoplasia and cryptorchidism were present in all boys (6/6). Dysmorphic features included a coarse face, a large nose with a high nasal bridge, and microcephaly. Other features included renal anomalies (multicystic kidneys or hydronephrosis, 7/7), agenesis of the corpus callosum (4/7), swallowing difficulties, micrognathia (4/7), and pulmonary hypoplasia (3/7). Bilateral hypoplasia of the ischia and brachydactyly were also consistently observed (5/5). In two out of seven cases, prenatal ultrasound detection of microcephaly and renal anomalies led to termination of the pregnancy at 27 weeks. Three children died during the first years of life and the remaining two who survived exhibit severe developmental delay. High resolution cytogenetic studies performed on lymphocytes or fibroblasts or both were normal in all cases. Recurrence in two families suggests an autosomal recessive mode of inheritance. We propose that this unusual association, similar to that observed in a 4 year old boy by Goldblatt et al, represents a new syndrome distinct from previously reported hypoplastic patella syndromes.


Keywords: patella; genital anomalies; renal anomalies; mental retardation     

Tricho-rhino-phalangeal syndrome type I with severe mental retardation due to interstitial deletion of 8q23.3-24.13

Here we report on a 13-year-old boy who had an interstitial deletion of the long arm of chromosome 8 [46,XY,del(8)(pter----q23.3::q24.13----qter)]. He had the facial features of the tricho-rhino-phalangeal (TRP) syndrome and severe mental retardation, but lacked multiple exostoses. This is the first report with such a peculiar combination of abnormalities and interstitial deletion of 8q.