Heterozygous pathogenic variants involving cause a new skeletal disorder resembling cleidocranial dysplasia.

Background: Cleidocranial dysplasia (CCD) is a rare skeletal dysplasia with significant clinical variability. Patients with CCD typically present with delayed closure of fontanels and cranial sutures, dental anomalies, clavicular hypoplasia or aplasia and short stature. Runt-related transcription factor 2 ( is currently the only known disease-causing gene for CCD, but several studies have suggested locus heterogeneity.

[C]-galactose breath test in a patient with galactokinase deficiency and spastic diparesis.

Galactokinase deficiency is an inborn error of carbohydrate metabolism due to a block in the formation of galactose-1-phosphate from galactose. Although the association of galactokinase deficiency with formation of cataracts is well established, the extent of the clinical phenotype is still under investigation. We describe a 6-year-old female who was diagnosed with galactokinase deficiency due to cataract formation when she was 10 months of age and initially started on galactose-restricted diet at that time for 5 months.

Jumonji domain containing 1C (JMJD1C) sequence variants in seven patients with autism spectrum disorder, intellectual disability and seizures.

The Jumonji domain containing 1C (JMJD1C) gene encodes the Jumonji domain-containing protein 1C (JMJD1C) and is a member of the jmJC domain-containing protein family involved in histone demethylation that is expressed in the brain. We report seven, unrelated patients with developmental delays or intellectual disability and heterozygous, de novo sequence variants in JMJD1C. All patients had developmental delays, but there were no consistent additional findings.

Variants in TCF20 in neurodevelopmental disability: description of 27 new patients and review of literature.

Purpose: To define the clinical characteristics of patients with variants in TCF20, we describe 27 patients, 26 of whom were identified via exome sequencing. We compare detailed clinical data with 17 previously reported patients.

Methods: Patients were ascertained through molecular testing laboratories performing exome sequencing (and other testing) with orthogonal confirmation; collaborating referring clinicians provided detailed clinical information.

Small Bowel Mucosal Involvement and Mesenteric Mass Formation in a Young Female with Type 3 Gaucher Disease. A Case Report.

Gaucher Disease arises due to a deficiency in the enzyme glucocerebrosidase and is the most common lysosomal storage disease. This enzyme deficiency leads to the accumulation of glucocerebroside within macrophages (Gaucher cells) and the resulting infiltration of these cells into organs can cause clinical symptoms. There are three types of Gaucher Disease that differ based on the clinical course and the presence or absence of neurological involvement, but classically, Gaucher cell infiltrates impact a patient's spleen, liver, bone marrow and cortex.

Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature.

Vici syndrome is a rare congenital disorder first described in 1988. To date, 31 cases have been reported in the literature. The characteristic features of this syndrome include: agenesis of the corpus callosum, albinism, cardiomyopathy, variable immunodeficiency, cataracts, and myopathy.

Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures.

Background: Joubert syndrome (JS) is a ciliopathy characterised by a distinctive brain malformation (the 'molar tooth sign'), developmental delay, abnormal eye movements and abnormal breathing pattern. Retinal dystrophy, cystic kidney disease, liver fibrosis and polydactyly are variably present, resulting in significant phenotypic heterogeneity and overlap with other ciliopathies. JS is also genetically heterogeneous, resulting from mutations in 13 genes.

Developmental delay timely identification and assessment.

This paper outlines the prevalence of developmental delay in children and discusses the recent literature regarding the benefits of early identification and evidence based strategies for developmental surveillance and screening. We describe a systematic approach to the child with developmental delay and the optimal methodology for arriving at the etiologic basis for the delay. A review of the most upto date and relevant literature was completed using Pub Med, online databases, and texts.

Incontinentia pigmenti with a foreshortened hand: evidence for the significance of NFkappaB in human morphogenesis.

The X-linked disorder incontinentia pigmenti (IP) with its well-defined underlying defect in the NFkappaB essential modulator (NEMO) gene and its variability in patients' phenotypes offers an excellent opportunity for expanding knowledge of the function of the NFkappaB pathway. We report a patient with the classic clinical and histologic characteristics of incontinentia pigmenti in the skin accompanied by foreshortening of the left hand. The occurrence of this limb deformity associated with a reduced expression of NFkappaB confirms the importance of this transcription factor in normal limb morphogenesis and may support its involvement in sonic hedgehog signaling.

Recurrent infections, hypotonia, and mental retardation caused by duplication of MECP2 and adjacent region in Xq28.

Objective: Our goal was to describe the neurologic and clinical features of affected males from families with X-linked patterns of severe mental retardation, hypotonia, recurrent respiratory infection, and microduplication of Xq28 that consistently includes the MECP2 (methyl-CpG binding protein 2) gene.

Study Design: To identify duplications, multiplex ligation-dependent probe amplification of the MECP2 gene was performed on male probands from families with X-linked mental retardation. The males either had linkage to Xq28 or had a phenotype consistent with previous reports involving Xq28 functional disomy.

Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation.

The rare, autosomal recessive Roberts syndrome (RBS) is characterized by tetraphocomelia, profound growth deficiency of prenatal onset, craniofacial anomalies, microcephaly, and mental deficiency. SC phocomelia (SC) has a milder phenotype, with a lesser degree of limb reduction and with survival to adulthood. Since heterochromatin repulsion (HR) is characteristic for both disorders and is not complemented in somatic-cell hybrids, it has been hypothesized that the disorders are allelic.

Characterization of a recurrent germ line mutation of the E-cadherin gene: implications for genetic testing and clinical management.

Purpose: To identify germ line CDH1 mutations in hereditary diffuse gastric cancer (HDGC) families and develop guidelines for management of at risk individuals.

Experimental Design: We ascertained 31 HDGC previously unreported families, including 10 isolated early-onset diffuse gastric cancer (DGC) cases. Screening for CDH1 germ line mutations was done by denaturing high-performance liquid chromatography and automated DNA sequencing.

Mosaic duplication 1(q11q44) in an infant with nephroblastomatosis and mineralization of extraplacental membranes.

Partial trisomy of 1q is rare. Only 32 cases of isolated partial trisomy 1q have been previously reported. From these cases, a characteristic phenotype is beginning to emerge.

Mutations in POMT1 are found in a minority of patients with Walker-Warburg syndrome.

Walker-Warburg syndrome (WWS) is an autosomal recessive disorder of infancy characterized by hydrocephalus, agyria, retinal dysplasia, congenital muscular dystrophy, and over migration of neurons through a disrupted pial surface resulting in leptomeningeal heterotopia. Although previous work identified mutations in the o-mannosyl transferase, POMT1, in 6 out of 30 WWS families [Beltran-Valero de Bernabe et al., 2002], the incidence of POMT1 mutations in WWS is not known.

[Chromosome microdeletions detected in mental retardation].

Objective: To explore whether chromosomal microdeletions have a role in the pathogenesis of unexplained mental retardation (MR) and the value of fluorescence in situ hybridization (FISH) in the detection of microdeletions in MR.

Methods: Selection of patients was based on the following criteria: (1) MR with two or more of the following: dysmorphic features, prenatal growth retardation, postnatal growth abnormalities, a suggestive family history; (2) Chromosome karyotype at the level >450 bands was normal; (3) Exclusion of other identified genetic or environmental diagnosis. FISH was carried out with specific DNA probe to 47 undiagnosed MR to identify interstitial microdeletions and further screen the integrity chromosome subtelomere.

[Chromosome subtelomeric analysis by FISH in patients with mental retardation].

Objective: To assess subtelomeric chromosome anomalies in patients with idiopathic mental retardation (MR).

Methods: Subtelomeric screening was performed in 46 patients with undiagnosed mental retardation. The patients were selected based on the following criteria: (1) MR with two or more of the following conditions: dysmorphic features, prenatal growth retardation, postnatal growth abnormalities, a suggestive family history; (2) chromosome karyotype at the level >450 bands being normal; (3) exclusion of other identified genetic or environmental diagnosis.

Fragile X syndrome and deletions in FMR1: new case and review of the literature.

The fragile X syndrome phenotype of mental retardation is almost always caused by abnormal CGG trinucleotide amplification within the FMR1 gene. Occasionally fragile X syndrome results from point mutations or deletions within or around the FMR1 locus. We have identified a mentally retarded African American male with typical fragile X phenotype and a 300-400 base pair intragenic deletion near the CGG repeat segment, present in his peripheral blood lymphocytes with no apparent mosaicism.

Genetic counseling in pediatric practice.

Genetic counseling can be incorporated into pediatric practice with relative ease. The pediatrician committed to caring for the "whole child" can ill-afford to overlook the medical and psychosocial impact of genetic disorders on his patients, their families and society at large. This article briefly reviews the rapidly growing field of genetic counseling as applied to pediatric practice.