A variant of uncertain significance of the HMGA2 gene in a child with Silver-Russell syndrome-like phenotype: a case report.

Silver-Russell syndrome 5 (SRS5) is characterized by asymmetric intrauterine growth restriction (IUGR), poor postnatal growth, macrocephaly at birth, and feeding difficulties. Other possible features include triangular shaped face, prominent forehead, hypertelorism, epicanthus, micrognathia, brachydactyly, clinodactyly of the 5th finger, and syndactyly of the 2nd and 3rd toes. Pathogenic variants of the HMGA2 (high mobility group AT-hook 2) gene, on chromosome 12q14, which regulates the transcription of growth factor IGF2, have recently been associated with this syndrome. Herein, we present a 2.5-year-old boy with growth delay, SRS-like phenotype, and a variant of uncertain significance in the HMGA2 gene, which has not, to the best of our knowledge, been described to date in the medical literature. So far, 28 pathogenic variants of the HMGA2 gene in patients with clinical SRS phenotype have recently been reported. Therefore, HMGA2 gene testing should always be done in SRS patients who are found to be negative for the typical 11p15 (epi)mutations and matUPD7, while the mutations should also be added to growth retardation disorder panels.

Congenital Hypopituitarism: Various Genes, Various Phenotypes.

The ontogenesis and development of the pituitary gland is a highly complex process that depends on a cascade of transcription factors and signaling molecules. Spontaneous mutations and transgenic murine models have demonstrated a role for many of these factors, including HESX1, PROP1, PIT1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, SHH, GLI2, and FGF8 in the etiology of congenital hypopituitarism. Genetic mutations in any of these factors can lead to congenital hypopituitarism, which is characterized by the deficiency in one or more pituitary hormones. The phenotype can be highly variable, consisting of isolated hypopituitarism or more complex disorders. The same phenotype can be attributed to different gene mutations; while a given gene mutation can induce different phenotypes. This review highlights the genetic variations that lead to congenital hypopituitarism and their associated defects. The overall incidence of mutations in known transcription factors in patients with hypopituitarism is low; therefore many gene mutations or even gene- epigenetic interactions have to be unraveled in the future to explain the vast majority of still unclear cases of congenital hypopituitarism.

Hypotonic hyporesponsive episode and the 13-valent pneumococcal vaccine.

Hypotensive-hyporesponsive episodes are rare events after immunizations performed for diphtheria, tetanus, Haemophilus influenzae type b and hepatitis B virus vaccines, but most of the reported episodes have been associated with pertussis-containing vaccines. We report the case of a 3-month-old girl, previously healthy otherwise, presenting with the unusual event of a hypotonic-hyporesponsive episode after vaccination with the 13-valent pneumococcal vaccine. Diagnosis was established after a thorough evaluation of the patient and by exclusion of other clinical conditions.

A girl with bilateral temporomandibular joint pain, generalized arthralgias, and inability to walk.

The authors present the case of a 6.5-year-old girl with bilateral temporomandibular joint (TMJ) pain, generalized arthralgias, inability to walk, and absence of deep tendon reflexes in the context of Guillain-Barrè syndrome. TMJ pain was the sole manifestation for 3 days, before other typical symptoms appeared, an issue that initially led to an improper diagnosis. A thorough clinical examination along with laboratory and radiographic evaluation excluded other possible causes of TMJ pain. To the best of the authors' knowledge, this is the first case of Guillain-Barrè syndrome in the pediatric population initially presenting with bilateral TMJ pain. Guillain-Barrè syndrome may be quite atypical in its expression, especially in young children, with pain being a common presenting symptom, and pediatricians should be alert to avoid misdiagnosis.

Timing of voiding cystourethrography in infants with first time urinary infection.

The aim of the study was to evaluate whether the timing of performing a voiding cystourethrography (VCUG) following a first urinary tract infection (UTI) in infants is related to the presence or the severity of vesicoureteral reflux (VUR). A total of 411 children (male 230, female 181) with a first-recognised UTI between ages 15 days and 12 months (median 3 months) underwent a VCUG within 4-81 days (median 9 days) following diagnosis. The presence and the grade of the VUR were compared in two groups: an "early" group in which the VCUG was performed during the first week of the start of treatment and a "late" group in which the examination was performed during the second week or thereafter. The prevalence of VUR in the study cohort was 23.3% (96/411 infants). A VUR was diagnosed in 44 infants in the early group (28%) and in 52 in the late group (21%). Reflux of grade III or higher was seen in 25/44 (57%) of the infants in the early group and in 27/52 (52%) infants in the late group. These differences were not significant. Our results suggest that neither the presence nor the grade of VUR in infants is influenced by the timing of the examination following diagnosis. We therefore recommend that it is better to perform VCUG as soon as possible, provided the inflammation has subsided.

Tall stature, insulin resistance, and disturbed behavior in a girl with the triple X syndrome harboring three SHOX genes: offspring of a father with mosaic Klinefelter syndrome but with two maternal X chromosomes.

AIMS: To describe the tall stature and its possible underlying mechanism in a Caucasian girl (age 12 years and 10 months) with 46,XX (28%)/47,XXX (72%) mosaicism and to identify the parental origin of her extra X chromosome. METHODS: The fasting glucose-to-insulin ratio was studied. The karyotypes of the girl and her parents as well as the presence of SHOX copies and the parental origin of her extra X chromosome were assessed. RESULTS: Clinical examination revealed a tall stature and severe acne, and endocrinological/metabolic assessment revealed insulin resistance. Fluorescence in situ hybridization cytogenetic analysis depicted the presence of three SHOX genes in the 47,XXX cell line of the patient. Karyotyping of her parents showed a normal 46,XX karyotype in the mother and 46,XY(93%)/47,XXY(7%) Klinefelter mosaicism in the father. However, DNA analysis unequivocally showed maternal origin of the extra X chromosome of the patient. CONCLUSIONS: This report suggests that SHOX gene triplication may produce a tall stature, even in the presence of preserved ovarian function. X triplication might predispose to insulin resistance and behavioral disorders.