Cleidocranial Dysplasia with 6p21.1-p12.3 Microdeletion: A Case Report and Literature Review.

OBJECTIVE: The aim of this article is to publish a literature review and report on a new case of cleidocranial dysplasia syndrome with 6p21.1-p12.3 microdeletion. DESIGN: A PubMed search using "cleidocranial dysplasia syndrome (CCD)" or "6p microdeletion" was performed. Articles with information relevant to our case were obtained for review. A new case of cleidocranial dysplasia syndrome is presented to describe and discuss clinical manifestations, pathogenesis, clinical progression of cleidocranial dysplasia syndrome, and management. RESULTS: There were 22 articles with reports of cleidocranial dysplasia syndrome or 6p microdeletion. Cleidocranial dysplasia syndrome, a rare genetic disorder, documented to have an autosomal dominant inheritance pattern and caused by caused by mutations of the transcription factor RUNX2. RUNX2 has been mapped to chromosome 6p21. The anomalies in cleidocranial dysplasia syndrome can involve not only the clavicle and skull but the entire skeleton because the membranous as well as endochondral bone formation may be affected. Upon follow-up, our patient was found to have global developmental delay. CONCLUSIONS: We report a near-term neonate with characteristic features of cleidocranial dysplasia and a 6p21.1-p12.3 microdeletion. Cleidocranial dysplasia syndrome is a rare autosomal dominant skeletal dysplasia. The mutation of the RUNX2 gene results in cleidocranial dysplasia syndrome.

7q21.11 Microdeletion in a Neonate With Goldenhar Syndrome: Case Report and a Literature Review.

The oculoauriculovertebral spectrum or Goldenhar syndrome is characterized by varying degrees of prevalently unilateral underdevelopment of the craniofacial structures (orbit, ear, and mandible) in association with vertebral, cardiac, renal, and central nervous system defects. We report on a term neonate with a partial monosomy 7q21.11 with marked hemifacial microsomia, facial clefting, and spinal anomaly. The estimated size of the monosomic region of 7q21.11 was approximately 55 kilobases. This is the first report of a patient with partial monosomy 7q21.11 associated with oculoauriculovertebral spectrum.

VATER/VACTERL Association and Caudal Regression with Xq25-q27.3 Microdeletion: A Case Report.

We report a term female neonate with vertebral anomalies, anal and urethral atresia, esophageal atresia with tracheoesophageal fistula (TEF), renal agenesis, pulmonary hypoplasia, genital and sacral appendages, and a single umbilical artery. Genetic studies revealed a 20.91 Mb interstitial deletion of the long arm of X chromosome: Xq25-q27.3. This is a new case of VATER/VACTERL association with Xq25 microdeletion.

OTX2 mutations contribute to the otocephaly-dysgnathia complex.

BACKGROUND: Otocephaly or dysgnathia complex is characterised by mandibular hypoplasia/agenesis, ear anomalies, microstomia, and microglossia; the molecular basis of this developmental defect is largely unknown in humans. METHODS AND RESULTS: This study reports a large family in which two cousins with micro/anophthalmia each gave birth to at least one child with otocephaly, suggesting a genetic relationship between anophthalmia and otocephaly. OTX2, a known microphthalmia locus, was screened in this family and a frameshifting mutation was found. The study subsequently identified in one unrelated otocephalic patient a sporadic OTX2 mutation. Because OTX2 mutations may not be sufficient to cause otocephaly, the study assayed the potential of otx2 to modify craniofacial phenotypes in the context of known otocephaly gene suppression in vivo. It was found that otx2 can interact genetically with pgap1, prrx1, and msx1 to exacerbate mandibular and midline defects during zebrafish development. However, sequencing of these loci in the OTX2-positive families did not unearth likely pathogenic lesions, suggesting further genetic heterogeneity and complexity. CONCLUSION: Identification of OTX2 involvement in otocephaly/dysgnathia in humans, even if loss of function mutations at this locus does not sufficiently explain the complex anatomical defects of these patients, suggests the requirement for a second genetic hit. Consistent with this notion, trans suppression of otx2 and other developmentally related genes recapitulate aspects of the otocephaly phenotype in zebrafish. This study highlights the combined utility of genetics and functional approaches to dissect both the regulatory pathways that govern craniofacial development and the genetics of this disease group.

Spondylocostal dysplasia and brachydactyly associated with TBX6 and IHH variants: A case report.

We report a preterm male neonate presenting with a short trunk, short neck, low hairline, deformed ears, preauricular skin tag, penoscrotal transposition (PT), palmar crease, short and broad fingers and toes (brachydactyly), hypoplastic and deep-set nails, metatarsal abductus, and cross-fused, small echogenic kidneys. Radiologic findings and genetic studies are consistent with spondylocostal dysostosis (SCD) and autosomal dominant brachydactyly. This is the first case report of spondylocostal dysostosis and brachydactyly associated with TBX6 and IHH variants. We reviewed the literature and compared our patient's phenotype with previously reported cases of SCD.

Prune Belly Syndrome Associated with Interstitial 17q12 Microdeletion.

We report a term male neonate presenting with a "prune belly," bilateral hydronephrosis, hydroureter, posterior urethral obstruction, and bilateral undescended testes. Analysis with the whole genome SNP microarray revealed an interstitial deletion of about 1.49 megabase (MB) at chromosome 17q12. We present a rare association of prune belly syndrome with a chromosomal deletion in this same region.

Four-vessel umbilical cord associated with multiple congenital anomalies: a case report and literature review.

A case is described of a neonate with a four-vessel umbilical cord containing two arteries and two veins. This was due to a rare persistence of the caudal portion of the right umbilical vein. The infant had multiple congenital anomalies including a complete atrioventricular canal, an interrupted inferior vena cava, a double superior vena cava, a left ventricular hypoplasia, dextrocardia, situs ambiguous, and malrotation of the small bowel. The birth of an infant with a four-vessel cord mandates comprehensive work-up for associated anomalies. The literature is reviewed.

Social and legal implications of urine drug screen analysis in the neonate: A case of suspected specimen mishandling.

BACKGROUND: The legal implications associated with illicit drug use during pregnancy are significant, as providers are required to notify child protective services when a drug-exposed infant is identified. CASE REPORT: The case presented involves possible specimen mishandling in two infants at risk for in utero drug exposure and describes alternative methodologies available to confirm specimen identity. CONCLUSIONS: It is critical that institutions establish and adhere to stringent procedures when screening newborns.

Multiple Congenital Anomalies in a Patient with Interstitial 6q26 Deletion.

We report a preterm male neonate presenting with a lumbosacral meningomyelocele, type II Arnold Chiari malformation, hypoplasia of the aortic arch, bicuspid aortic valve, ventricular septal defect, secundum atrial septal defect, multicystic dysplastic kidney, and hydronephrosis. Analysis with whole genome SNP microarray revealed an interstitial deletion of about 237 kb in chromosome 6q26. Long contiguous stretches of homozygosity (>3 Mb) were seen in 18 chromosomes with a total genomic size of 219 Mb. The phenotype seen in our patient has not been reported in association with the genes in the homozygous regions. However, our patient shares many phenotypic features with other reported cases that have shown a deletion in the same region of chromosome 6.

Partial trisomy 19p13.3 and partial monosomy 1p36.3: Clinical report and a literature review.

We report on a 15-month-old girl with a deletion of the distal short arm of chromosome 1p36.3, partial trisomy of the short arm of chromosome 19p13.3, growth and developmental delay, and multiple anomalies including microcephaly, bifrontal prominence, obtuse frontonasal angle, short columella, hypertelorism, sacral dimples, and a bicuspid pulmonary valve. Based on our FISH mapping studies, we estimate the size of the trisomic region of 19p.13.3 to be approximately 3.17 Mb, and the region of monosomy for 1p36.3 as 1.3 Mb. This is the first report of a patient with partial trisomy 19p13.3 and partial monosomy p36.3.

Calcified meconium balls in a newborn: an unusual case with imperforate anus, rectourinary fistula, colpocephaly, and agenesis of corpus callosum.

Calcified intraluminal meconium is a rare finding in newborn infants. It is often associated with communication between the urinary and gastrointestinal tracts. Intra-abdominal calcifications are unusual radiographic findings in the newborn and can easily be misinterpreted as meconium peritonitis. We report on a newborn infant with anorectal malformation, meconium balls, intraluminal calcifications, colpocephaly, and agenesis of the corpus callosum, a rare association.

8p 11 Microduplication Is Associated with Neonatal Stridor.

We report a term male infant with congenital stridor secondary to tracheomalacia and a mild coarctation of the aorta. Developmental delay was noted upon follow-up. Whole genome SNP microarray analysis showed an ∼846-kb interstitial duplication of the short arm of chromosome 8 (8p11.21p11.1). We report novel clinical findings of this rare genetic condition.

Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Meningitis and Cerebral Abscess in a Neonate: Therapeutic Challenge.

We report a case of a 12-day-old term neonate with extended-spectrum beta-lactamase (ESBL) producing Escherichia coli (E. coli) meningitis and cerebral abscess. The patient received a 7-day course of antibiotics just few days prior to the infection. The incidence of infections from ESBL-producing E. coli is increasingly emerging. Antimicrobial agents must be vigilantly utilized to prevent the new highly resistant bacteria.

Fracture of a Broviac catheter in a low-birth-weight infant.

Central venous catheters are widely used in children, particularly in very-low-birth-weight infants in whom long-term access to the venous system is required. This may be achieved by using peripherally inserted central catheters or tunnelled central venous lines (eg Broviac or Hickman lines). Previous case reports of fractured central catheters in premature neonates have involved peripherally inserted silastic catheters. Fractures and embolisation of Broviac central venous fragments have not been previously reported in preterm neonates. We describe a premature neonate with this rare complication along with the retrieval technique used.

Ventriculomegaly and cerebellar hypoplasia in a neonate with interstitial 11q 24 deletion in Jacobsen syndrome region.

Jacobsen syndrome (JS) is a rare contiguous gene disorder caused by partial deletion of the distal part of the long arm of chromosome 11 ranging in size from 7 to 20 Mb. We report a term male neonate with an interstitial deletion of about 12.3 megabase (Mb) of chromosome 11q24.1qter. Our case is the first reported newborn patient with 11q24 deletion.

Biliary Tract Abnormalities as a Cause of Distal Bowel Gas in Neonatal Duodenal Atresia.

BACKGROUND: The presence of distal bowel gas in an infant does not exclude the diagnosis of duodenal atresia. CASE PRESENTATION: We report a term neonate with Down syndrome. The infant developed vomiting and cyanosis with each feeding soon after birth. Plain film abdominal X-rays showed a nonspecific gas-filled stomach and small bowel. Duodenal atresia and an anomalous common bile were noted on an upper GI study and exploratory laparotomy. CONCLUSION: In the absence of a "double bubble" appearance and intestinal gas distally on a plain radiograph, one must not exclude duodenal atresia as the differential diagnosis.

Pulmonary Vasculitis and a Horseshoe Kidney in Noonan Syndrome.

We report a term male neonate with congenital myeloproliferative disorder, thrombocytopenia, a horseshoe kidney, feeding difficulty secondary to dysphagia/foregut dysmotility, and respiratory failure. Prenatal molecular genetic analysis revealed a fetus carrying c.184T>G (p.Tyr62Asp) pathogenic variant in PTPN11. The infant eventually succumbed to respiratory failure. Bacterial and viral cultures/studies were all no growth/negative. Pulmonary capillaritis and vasculitis were noted at autopsy. This report presents a new case of Noonan syndrome with unusual associated disorders and a review of the literature.

11p15.4 Microdeletion Associates with Hemihypertrophy.

We report a preterm female infant with intrauterine growth retardation, dysmorphic facies, missing rib, small hands and feet, and hemihypertrophy. The results of whole genome SNP microarray analysis showed approximately 77 Kb interstitial deletion of the short arm of chromosome 11 (11p15.4). We report novel clinical findings of this rare genetic condition.

A Giant Gastroschisis Associated with Pulmonary Hypoplasia and Spinal Anomaly: A Case Report and a Literature Review.

Gastroschisis most often occurs as an isolated anomaly and extragastrointestinal associations are rare. Most commonly, the anomalies associated with gastroschisis are cardiac and central nervous system abnormalities. Respiratory insufficiency has sometimes been reported in association with giant abdominal wall defects. Poor outcomes and prolonged ventilator support have been reported in giant gastroschisis and omphalocele, especially if associated with herniation of the majority of the liver. We report a case of a large gastroschisis that was associated with a kyphoscoliosis and pulmonary hypoplasia.