Microcephaly associated with Legg-Calvè-Perthes disease in two siblings
Salvatore Savasta1, Martino Ruggieri, Piero Pavone
1Department of Pediatrics, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy.
Summary
This study documents a second family with microcephaly and Legg-Calvè-Perthes disease (LCPD), revealing complex brain malformations in affected siblings. The findings highlight a rare genetic link between these conditions.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Familial co-occurrence of microcephaly and Legg-Calvè-Perthes disease (LCPD) is exceptionally rare, with only one prior report.
- Investigating familial cases is crucial for understanding the genetic basis and phenotypic spectrum of combined disorders.
Observation:
- A second family with two siblings presenting with primary microcephaly and LCPD was identified.
- Clinical evaluation included neurological assessments, seizures, and mild-to-moderate intellectual disability.
- Radiological assessment involved X-ray, MRI, revealing distinct brain malformations in both siblings.
Findings:
- The male sibling exhibited skull asymmetry, frontal lobe developmental issues, and partial agenesis of the corpus callosum.
- The female sibling presented with complex brain malformations including cortical thickening, colpocephaly, and cerebellar hypoplasia.
- Both siblings displayed primary microcephaly, with the brother also diagnosed with ADHD and the sister with minor eye anomalies.
Implications:
- This report provides the first documented family with LCPD and microcephaly showing complex brain anomalies via MRI.
- The findings suggest a potential shared genetic etiology or a complex interplay between microcephaly and LCPD.
- Further research into similar cases is encouraged to elucidate the underlying mechanisms and genetic factors involved.
Related Concept Videos
02:30Genomic Imprinting and Inheritance
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:27Cytomegalovirus Disease
Cytomegalovirus (CMV) disease is caused by human cytomegalovirus, a double-stranded DNA virus of the Herpesviridae family. While primary CMV infection is often asymptomatic in immunocompetent individuals, the virus can cause severe disease in neonates and immunocompromised patients. CMV is the most common cause of congenital viral infection in the United States, and a major pathogen in solid organ and hematopoietic stem cell transplant recipients.CMV is transmitted via bodily fluids, sexual...
01:43Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
01:20Inborn Errors of Metabolism
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...