Miller Dieker Syndrome

INTRODUCTION. Idiopathic congenital nystagmus, or idiopathic infantile nystagmus is a disease characterized by the rapid, involuntary eye movement. This movement is typically in the horizontal direction, however, movement in other directions have been observed. One way to get nystagmus is through genetic mutations. Nystagmus caused by genetic mutation is seen at a relatively young age but cannot yet be treated. The disease is not understood well, it is believed that the cause is a developmental defect. The linkage, and inheritance has not been identified, the patterns suggest that multiple genes are involved in the disease and that there are loci on different chromosomes with three of the five loci located on the X chromosome. Mutations have been linked to the FRMD7 gene, a gene that consists of 12 exons, of the FERM family. The function of FRMD7 have yet to be determined however an abundance of the protein in the brain in areas associated with the eye. Mutations within this region consist of missense, deletion, tranversion and nonsense mutations. Over forty-four mutations that lead to ICN have been found in the FRMD7 gene. Learning more about the mutation of FRMD7 in ICN is important because these mutations may prevent elongation of neurite processes during differentiation preventing axons from responding to stimuli (Watkins et al. 2012).

These include motor neuron disease, corticobasal syndrome, progressive supranuclear palsy and FTDP-17 (FTD with parkinsonism linked to chromosome 17).

The purpose of this paper is to discuss the effects of the disorder and how genetics and biochemistry work together to create this

Dandy-Walker Syndrome or Dandy-Walker Malformation is a congenital malformation of the cerebellum and the fluid filled space surrounding it. The malformation can include an enlargement of the fourth ventricle, a partial or complete absence of the space between the two hemispheres of the cerebellum (called the vermis), and a cyst formation near the lowest part of the skull (National Institute of Neurological Disorders and Stroke [NINDS], 2016). Dandy-Walker Syndrome is found in approximately 1 of 25,000 to 35,000 live births and is more prevalent in females than males (NORD-National Organization for Rare Disorders, 2008). Although an exact case is not known, the syndrome may be a result of defects in the embryonic development of the cerebellum. Research has found that in some cases patients have chromosomal abnormalities. Dandy-Walker may also be caused by genetic abnormalities or environmental factors, teratogens (NORD-National Organization for Rare Disorders, 2008). Maternal diabetes and infections passed through the mother to the fetus may also result in a child born with Dandy-Walker Syndrome (Childrens National Health System, 2016).

In 1995 a French group of researchers discovered that SMA is autosomal recessive disorder due to loss of the survival motor neuron protein gene (SMN) (Lefebvre et al., 1995). Through experimentation the researchers discovered two copies of the SMN gene in chromosome five [chr 5q13.2]: telomeric and centromeric SMN copies. Experimentation proved that loss of the telomeric SMN (today known as SMN1) and not loss of its centromeric counterpart, SMN2, resulted in SMA.

DIAGNOSTIC CRITERIA: Prenatal onset of marked growth deficiency, microcephaly with secondary premature synostosis. Receding forehead, prominent nose micrognathia low set ears malformed ears with the lack of lobule down slanting palpebral fissures. Clinodactyly of fifth finger

ABSTRACT: Mutations in the MED12 gene are associated with X-linked intellectual disability (ID) which present phenotypically as FG syndrome or Lujan syndrome. The two disorders have overlapping features of ID, hypotonia, and corpus callosum abnormalities but physical features differ . Carrier females are typically unaffected. Mitochondrial dysfunction has not been previously described. Herein, we report a 7 year old male with features of FG syndrome, hypogammoglobulinemia, mitochondrial dysfunction, and normal IQ found to have a de novo deleterious MED12 mutation on whole exome sequencing. This case expands the phenotype of MED12-related disorders. In addition, hypogammoglobulinemia documented in this patient may explain the frequent infections reported in other patients with MED12 mutations.

Seckel Syndrome reported by Mann and Russel in 1959, this condition was extensively studied by Seckel in 1960. More precise criteria for diagnosis have been recently been set forth.

Wolman is a very rare disease. Involves conditions of the breakdown, and use of fat and cholesterol in the body. The people who are affected by this get harmful amount of lipids accumulate in the spleen, liver, bone marrow, small intestine, small hormone-producing glands on top of each kidney, and lymph nodes. Adrenal glands are also seen.

Prior to the study, it was known that chromosomal rearrangements within the 22q11.2 locus have been associated with an increased risk of neurodevelopmental disorders. Specifically, 22q11.2 deletion holds the greatest risk for schizophrenia, approximately 30 times the risk, while 22q11.2 duplication is associated with autism and delays in psychomotor development and language. This study was the first to look at the effect of 22q11.2 (deletions and duplications) on brain morphology.

There are thousands of rare diseases known to mam kind that only affects one of every couple thousand people. Each of which have their own unique characteristics that define each disease from one another. The one disease that is closest to my last name is the Smith-Magenis Syndrome also known as (SMS). However, 1 in 25,000 are considered to have this condition but are currently not diagnosed with the disease. Although, many officials believe the number is closer to 1 in 15,000. Currently there have been no signs of this disease being inherited through genetics, this disease is caused by a deletion of a region of chromosomes. The Smith-Magenis Syndrome is a development disorder that has multiple effects on an infected person through physical appearances, speech and sleep disorders, and behavioral problems.

This is a genetic disorder caused by a missing piece of chromosome 4. It is a rare disease and only affects about 1:50,000 births. The result of this missing piece on the short arm of chromosome 4 is a wide range of physical and developmental symptoms and impairments. These include microcephaly, slow growth in utero and postpartum, hypotonia, seizures, profound intellectual disability, cryptorchidism, and hypospadias, amongst many others. In addition, the child tends to have distinct facial features---“Greek Helmet Facies”--- including a broad nose, cranial asymmetry, hypertelorism, micrognathia, abnormal upper lips, cleft lip and/or cleft palate, and preauricular tags and/or pits. The list of remaining signs and symptoms is too long to this for the purposes of this assignment so I have listed some of the more common ones, knowing that each child may exhibit a different cluster of symptoms. Initial signs of the disease are found during pre-natal ultrasounds but it can only be confirmed through genetic testing. (Wolf-Hirschorn syndrome, n.d.)

For the purpose of this case study a focus will be placed upon the PRS and associated chromosomal deletions, which have caused global developmental delays, learning delays and present Jane with social and emotional challenges. Also considered will be the Duanes Syndrome and resulting visual impairment.

One rare, but extremely fatal chromosomal disorder is Edwards Syndrome (Trisomy 18). “A trisomy is caused by a genetic error in which three copies of a chromosome (instead of two) are inherited from the parents.” (Perlstein, D.) This disorder is the second most common trisomy, first being Down Syndrome. The two disorder are very common, however, Edwards Syndrome is much more fatal and life-threatening. “Today the majority of fetuses with Trisomy 18 are diagnosed prior to birth.” (Perlstein, D.)

Jacobsen syndrome was discovered by Dr. Petra Jacobsen in 1973, as he describes a family with multiple members who had an unbalanced 11;21 chromosome, which had originated from a balanced translocation carrier parent. There are some patients with large deletions that can exhibit severe clinical manifestations and impairments, however, a few phenotypes reveal incomplete penetrance can differ greatly between several patients.