No abstract available.
Wolf-Hirschhorn Syndrome*

The 4p deletion syndrome, also known as Wolf-Hirschhorn syndrome, is a well-known genetic disorder caused by a partial deletion of the short arm of chromosome 4. The great variability in the extent of the 4p deletion and the possible contribution of additional genetic rearrangements leads to a wide spectrum of clinical manifestations. Herein, we present our experience with eight cases of 4p deletion syndrome, ascertained prenatally between 1998 and 2016 at our hospital.
Arm ; Chromosomes, Human, Pair 4 ; Prenatal Diagnosis* ; Wolf-Hirschhorn Syndrome*

Wolf-Hirschhorn syndrome is a multiple malformation syndrome associated with mental and developmental retardation, resulting from a deletion at the short arm of chromosome 4 (4p16.3). We report a 11-year-old girl with Wolf-Hirschhorn syndrome, who was presented with severe growth and mental retardation along with characteristic features-frontal bossing, hypertelorism, downslanting of the palpebral fissures and fishlike lips. The diagnosis was confirmed by fluorescent in-situ hybridization (FISH).
Arm ; Child ; Chromosomes, Human, Pair 4 ; Diagnosis ; Female ; Humans ; Hypertelorism ; Intellectual Disability ; Lip ; Wolf-Hirschhorn Syndrome*

Wolf-Hirschhorn syndrome is a multiple malformation syndrome associated with mental and developmental retardation, resulting from a deletion at the short arm of chromosome 4 (4p16.3). We report a 11-year-old girl with Wolf-Hirschhorn syndrome, who was presented with severe growth and mental retardation along with characteristic features-frontal bossing, hypertelorism, downslanting of the palpebral fissures and fishlike lips. The diagnosis was confirmed by fluorescent in-situ hybridization (FISH).
Arm ; Child ; Chromosomes, Human, Pair 4 ; Diagnosis ; Female ; Humans ; Hypertelorism ; Intellectual Disability ; Lip ; Wolf-Hirschhorn Syndrome*

Comparative Genomic Hybridization ; methods ; Female ; Humans ; Infant ; Wolf-Hirschhorn Syndrome ; diagnosis

Wolf-Hirschhorn syndrome is a well-recognized malformation syndrome with multiple congenital anomalies, resulting from partial deletion of the short arm of chromosome 4 (4p-). All affected individuals have intrauterine and postnatal growth retardation with marked feeding difficulties, developmental delay, and intellectual disability. Additionally, most of patients have seizures from early infancy. Although seizures are common with this syndrome, presenting with status epilepticus (SE) is rare. We report two cases of Wolf-Hirschhorn syndrome presenting with SE.
Arm ; Chromosome Deletion ; Chromosomes, Human, Pair 4 ; Humans ; Intellectual Disability ; Seizures ; Status Epilepticus ; Wolf-Hirschhorn Syndrome

Wolf-Hirschhorn syndrome is caused by a partial loss of the distal short arm of chromosome 4. Characteristic clinical features are severe growth retardation, mental retardation, seizures, congenital cardiac defects, urogenital abnormalities, microcephaly, hypertelorism, prominent glabella, cleft lip and palate and micrognathia. In 87% of cases, chromosome 4 deletion arises as a de novo event, whereas in the remaining cases it is derived from a familial balanced translocation. Chromosomal study of the patient showed 46 XX der(4)t(4;18)(p15.2;q23), and the patient's mother was found to have a balanced translocation, 46 XX t(4;18)(p15.2;q23).
Arm ; Chromosomes, Human, Pair 4 ; Cleft Lip ; Humans ; Hypertelorism ; Intellectual Disability ; Microcephaly ; Mothers ; Palate ; Seizures ; Urogenital Abnormalities ; Wolf-Hirschhorn Syndrome*

BACKGROUNDWolf-Hirschhorn syndrome (WHS) results from the partial deletion of 4p. This study aimed to identify and fine map the chromosome deletion regions of Chinese children with Wolf-Hirschhorn syndrome among the developmental delay/mental retardation (DD/MR) patients.

METHODSWe analyzed the relationship of phenotype and genotype. Inclusion criteria were: moderate to severe DD/MR, no definite perinatal brain injury, and no trauma, toxication, hypoxia, infection of central nervous system; routine karyotyping was normal, no evidence of typical inherited metabolic disorder or specific neurodegenerative disorders from cranial neuro-imaging and blood/urinary metabolic diseases screening; no mutation of FMR1 in male patients, no typical clinical manifestation of Rett syndrome in female patients. Multiplex ligation-dependent probe amplification (MLPA) and Affymetrix genome-wide human SNP array 6.0 assays were applied to accurately define the exact size of subtelomeric aberration region of four WHS patients.

RESULTSAll four WHS patients presented with severe DD, hypotonia and microcephaly, failure to thrive, 3/4 patients with typical facial features and seizures, 2/4 patients with congenital heart defects and cleft lip/palate, 1/4 patients with other malformations. The length of the deletions ranged from 3.3 Mb to 9.8 Mb. Two of four patients had "classic" WHS, 1/4 patients had "mild"-to-"classic" WHS, and 1/4 patients had "mild" WHS.

CONCLUSIONSWHS patients in China appear to be consistent with those previously reported. The prevalence of signs and symptoms, distribution of cases between "mild" and "classic" WHS, and the correlation between length of deletion and severity of disease of these patients were all similar to those of the patients from other populations.

Adolescent ; Child ; Female ; Genotype ; Humans ; Male ; Mutation ; Phenotype ; Polymorphism, Single Nucleotide ; genetics ; Wolf-Hirschhorn Syndrome ; genetics ; pathology

PURPOSE: Lactic acidosis is one of the most common forms of metabolic acidosis. It is hard to fine the cause of lactic acidosis, because in many cases the clinical features of this disorder are non-specific and overlap with those of other metabolic or non-metabolic diseases. In this report, we tried to identify the causes of lactic acidosis and classified them into four groups:primary and secondary lactic acidosis, neurodegenerative disorders and others. METHODS: We analyzed the clinical characteristics of 22 patients who had arterial blood lactate levels over 2.5 mmol/L. They visited Ilsan Hospital because of seizures or delayed development. Clinical characteristics include laboratory findings, EEG, brain imaging study, chromosomal study and metabolic enzymatic evaluation. RESULTS: The mean age of the patients was 3.4 years. Most of them complained of delayed development(21 cases) and seizures(14 cases). One of the patients was revealed as primary lactic acidosis, and the other one secondary lactic acidosis. Also, there was a case of neurodegenerative disease. Furthermore, the other ten patients were affected by other causes of lactic acidosis:7 cases of epilepsy, a case of Rett syndrome, a case of 4p deletion syndrome, and a case of cerebral palsy. However, the causes of lactic acidosis of the remaining 9 patients were unknown. But 5 of them were thought to be affected by respiratory chain disorders diagnosed by modified Walker's criteria. CONCLUSION: There are numerous disorders in children which can produce lactic acidosis. Although metabolic work-ups of these patients are very complex and require coordinated efforts of clinicians and laboratory works, early diagnosis of the etiologic nature of the disease is essential to minimize the progression and the complications of the disease.
Acidosis ; Acidosis, Lactic* ; Cerebral Palsy ; Child* ; Early Diagnosis ; Electroencephalography ; Electron Transport ; Epilepsy ; Humans ; Lactic Acid ; Mitochondrial Diseases ; Neurodegenerative Diseases ; Neuroimaging ; Rett Syndrome ; Seizures ; Wolf-Hirschhorn Syndrome

OBJECTIVETo screen for genomic copy number variants (CNVs) in a fetus with cardiac abnormalities and intrauterine growth retardation through single nucleotide polymorphism microarray (SNP array) and karyotyping analysis.

METHODSThe fetus and its parents were subjected to conventional G banding and SNP-array analysis. The results were confirmed with fluorescence in situ hybridization (FISH).

RESULTSG-banding analysis showed that the fetus has a karyotype of 47,XX,+mar. The father has a karyotype of 46,XY,t(4;18) (p15.2q11.2), while the mother showed a normal karyotype. SNP-array detected two microduplications at 18p11.32q11.2 (20.5 Mb) and 4p16.3p15.2 (24.7 Mb) in the fetus. The supernumerary marker chromosome carried by the fetus has derived from the balanced translocation carried by its father. The result was confirmed by FISH.

CONCLUSIONBased on the two microduplications, the fetus was diagnosed as Wolf-Hirschhorn syndrome in conjunction with Edward syndrome. Verification of the origin of the supernumerary marker chromosome by SNP-array has provided a basis for prenatal genetic diagnosis.

Chromosome Banding ; Female ; Genetic Testing ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; Trisomy 18 Syndrome ; genetics ; Wolf-Hirschhorn Syndrome ; genetics