Index of suspicion.

Case 1: Facial and upper extremity weakness in a 16-year-old boy. Case 2: Hematochezia in a neonate. Case 3: bad body odor in a 13-year-old girl.

Duplication of the STS region in males is a benign copy-number variant.

Copy-number variants (CNVs) are a common finding in the human genome, with copy gains occurring at a higher frequency than losses in several databases of genomic variants in normal individuals. Copy gains of the steroid sulfatase (STS) gene have been seen in both males and females. Although deletion of STS in males is known to cause X-linked ichthyosis, the clinical significance of STS copy gains is less clear, with the duplication reported in individuals with abnormal phenotypes and normal relatives.

Microduplication of 4p16.3 due to an unbalanced translocation resulting in a mild phenotype.

With the widespread clinical use of comparative genomic hybridization chromosomal microarray technology, several previously unidentified clinically significant submicroscopic chromosome abnormalities have been discovered. Specifically, there have been reports of clinically significant microduplications found in regions of known microdeletion syndromes. In general, these microduplications have distinct features from those described in the corresponding microdeletion syndromes.

Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a neurobehavioral disorder manifested by infantile hypotonia and feeding difficulties in infancy, followed by morbid obesity secondary to hyperphagia. It is caused by deficiency of paternally expressed transcript(s) within the human chromosome region 15q11.2.

Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency.

Systemic primary carnitine deficiency (CDSP) is caused by recessive mutations in the SLC22A5 (OCTN2) gene encoding the plasmalemmal carnitine transporter and characterized by hypoketotic hypoglycemia, and skeletal and cardiac myopathy. The entire coding regions of the OCTN2 gene were sequenced in 143 unrelated subjects suspected of having CDSP. In 70 unrelated infants evaluated because of abnormal newborn screening (NBS) results, 48 were found to have at least 1 mutation/unclassified missense variant.

Hepatic failure, neonatal hemochromatosis and porto-pulmonary hypertension in a newborn with trisomy 21--a case report.

Liver failure in neonates is a rare but often fatal disease. Trisomy 21 is not usually associated with significant infantile liver disease. If present, hepatic dysfunction in an infant with Trisomy 21 is likely to be attributed to transient myeloproliferative disorder with hepatic infiltration by hematopoietic elements and may be associated with secondary hemosiderosis.

Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects.

Background: Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the SLC22A5 gene that encodes the carnitine transporter, organic cation transporter. Systemic primary carnitine deficiency typically presents in childhood with either metabolic decompensation or cardiomyopathy. We report five families in which low free carnitine levels in the infants' newborn screening have led to the diagnosis of maternal systemic primary carnitine deficiency.

Growth spurt hypocalcemia.

This is a clinical presentation of a healthy 12-year-old African-American male who had symptomatic hypocalcemia during a growth spurt that resolved after reaching a stable height. He had clinical findings consistent with Pseudohypoparathyroidism (PHP) with hypocalcemia, hyperphospatemia, and increased parathyroid hormone (PTH) concentration. We hypothesize that his family might have a hitherto unreported autosomal dominant PHP-Ib that may or may not be linked to the GNAS locus.

Memory and learning in children with 22q11.2 deletion syndrome: evidence for ventral and dorsal stream disruption?

This study examined memory functioning in children and adolescents with 22q11.2 Deletion Syndrome (DS; velocardiofacial syndrome). An overall verbal better than nonverbal memory pattern was evident on the Test of Memory and Learning (TOMAL), with children with 22q11.

Transmission of ring chromosome 13 from a mother to daughter with both having a 46,XX, r(13)(p13q34) karyotype.

Ring chromosomes are thought to be the result of breakage in both arms of a chromosome, with fusion of the points of fracture and loss of the distal fragments. Another mechanism of ring formation is believed to be the simple fusion of chromosome ends with preservation of telomeric and subtelomeric sequences. Ring chromosome 13 was first described in 1968 and its incidence estimated at 1 in 58,000 live births.

Medulloblastoma with adverse reaction to radiation therapy in nijmegen breakage syndrome.

A 3-year-old child with microcephaly, facial dysmorphism, growth retardation, and developmental delay was diagnosed with medulloblastoma. Craniospinal irradiation resulted in severe radiation-induced dermatitis and gastroesophagitis, unresponsive to further medical therapy. Colony survival assay on the patient's transformed lymphocytes revealed a high degree of radiosensitivity ex vivo.

Evaluation of surgical intervention in familial isolated simple ectopia lentis: younger v. older generations.

Background: There continues to be a debate whether surgical management of ectopia lentis in children is an appropriate course to improve visual acuity and prevent further amblyopia over medical and optical management. The long term outcome and postoperative status of three generations of patients in a single family with simple ectopia lentis is presented.

Subjects: Nine family members (ages 6-61 years) were evaluated at Children's Hospital of Michigan (CHM) (6 patients) and Kresge Eye Institute (KEI) (3 patients) for primary or secondary visual acuity problems and a family history of simple bilateral ectopia lentis without any systemic manifestations.