Nail-Patella Syndrome: A Case Study

Type II syndactyly or synpolydactyly(SPD) is a semi dominant inherited limb malformation that involves a fusion of digits. It is caused by mutations in HOXD13 on chromosome 2 due to polyalanine repeat expansions. Polyalanine repeats in SPD are mitotically and meiotically stable, causing polymorphisms to be rare, unlike other nucleotide repeat expansions such as Friedreich’s ataxia. HOXD13 is a member of the HOX family, a family of transcription factors that are proteins which contain homeodomain that are important for controlling cell fate along the limb axes and body. HOXD13 is a part of the HOXD gene cluster and crucial for limb development, particularly during the early and late stages of limb development. The stage occurs during the creation of the limb buds at week 4, during this stage the limbs have AP polarity through the expression of sonic hedgehog(shh) signaling from the zone of polarizing

The causation of MD covers a broad spectrum, hence it may be classified as a syndrome. In this section we summarize the predisposing factors of MD and focus on genetic factors.

Achondroplasia (ACH) is the most common form of short-limb dwarfism occuring in 1 in 15,000 to 28,000 births and appears to be slightly more prevalent in females, but indiscriminent toward race (1-3). Evidence has been found in Egypt for cases of ACH dating back as far as 4500 B.C. (4). In simplest terms, ACH is a disease where the dwarfing of bones formed in the cartilage occurs (5). There are many features that accompany this disease including rhizomelic (proximal) shortening of the extremities, megalencephaly (enlarged brain), short stature, trident hand, and frontal bossing (prominent forehead) (1, 3, 4, 6-8). Expression of this gene at high levels is primarily found in cells of the nervous system and the cartilage rudiments and

In the lab, we looked in the microscope at many different types of tissues such as epithelial, connective, and muscle. Within connective tissues, there are many tissue disorders that can affect your muscles, joints, or skin also your organs and organ systems. One connective tissue disease that I found was Marfan syndrome. Marfan syndrome is an inherited disorder that affects the connective tissue. Marfan syndrome affects about 1 in every 5000 people. People that have marfan syndrome usually have trouble with their eyes, heart, skeleton, and blood vessels. They are also known to have very long and unproportioned arms and legs and long spider- like fingers and toes. They can also have crowded teeth, sunken or bulging chest, flat feet, scoliosis, and many other different problems. These are just some of

Witkop syndrome is manifested by defects in the nail plates of fingers and toes typically and hypodontia, with normal hair and sweat gland function. There is a pattern of missing teeth.8 Absent maxillary incisors, second molars, and maxillary canines are the most common missing teeth.9 Genetically, mutations in genes MSX-1, PAX9, PsITX2, LTBP3, WNT10A, EDA and EDARADD, AXIN2, and IKBKG have been found associated with oligodontia. Mutations in MSX-1 have been shown to be associated with Witkop’s syndrome.[10)

Mutations of the GL13 gene during development is known to cause this disorder. It is known to be involved in the patterning of tissues and organs. It helps by helping to control whether specific genes are turned off or on. This condition can also be inherited.

A genetic disorder is a genetic condition, originally caused by a DNA abnormality. Genetic disorders can be inherited or can form early, in the development of child’s womb. Marfan syndrome is a genetic disorder that affects the body’s connective tissues in many parts of the human body. These specific connective tissues are made with the help of fibrillin, to produce elastic fibers, which are essential for connective tissues. The connective tissues are the tissues that provide strength and flexibility to many structures such as the bones, blood vessels, ligaments, muscles, and heart vessels. Connective tissues also allow the body to grow and develop properly. Marfan syndrome occurs when there is a mutation in the gene, specifically what tells

Dwarfism is a syndrome where a person has abnormal bone development. Symptoms include short stature, bowed legs, curvature of the lower spine, and a prominent forehead. The most common type of dwarfism, Achondroplasia, is characterized by a glycine to arginine mutation on codon 380 in the fibroblast growth factor receptor transmembrane domain 3 gene. When the mutated fibroblast growth factor receptor 3 protein interacts with a fibroblast growth factor ligand, the receptor is stabilized and a cascade of events occur. Downstream receptor pathways that are affected by the mutation involve signal transducer and activator of transcription 1 and phospholipase C, gamma 1. Different mutations on the fibroblast growth factor receptor transmembrane

Polydactyly is one of the most common hereditary limb malformations and it is characterized by additional digits in the hands and/or the feet. It primarily presents as an additional pre-axial or post-axial digit. Polydactyly is a highly heterogeneous condition and shows a broad inter- and intra-familial clinical variability. Pre-axial polydactyly II (OMIM 174500), also known as triphalangeal thumb polydactyly, is a disease in which the biphalangeal thumb is replaced by an triphalangeal thumb with a normal metacarpal bone. In some cases, there is also duplication of the great toe. Pre-axial polydactyly II is caused by heterozygous mutations in a Sonic hedgehog (SHH) enhancer element located in intron 5 of the LMBR1 gene on chromosome 7q36.3.

The Mutation is currently unknown and unmapped. Diagnosis is based entirely on beighton scale, clinical examination, and family history. Hypermobility type is classified in order of occurrence; Generalised joint hypermobility, recurrent joint dislocations and subluxations, chronic pain, musculoskeletal pain, bruising tendencies. Treatment often includes assistive devices such as crutches or wheelchairs to avoid stressing joints, braces and bandaging of joints, anti inflammatory drugs to reduce pain and swelling, calcium and vitamin D can also be used for bone

As mentioned before, MLIV is a rare autosomal recessive disorder. The gene affected is the MCOLN1 gene, which is located on chromosome 19p13.2–13.3. The MCOLN1 gene is around 12 kb and contains 14 exons (1). The most common pathogenic variant of the mutation involves splice variant c.406-2A>G. This splice variant prevents splicing of the mRNA encoding TRPML1 at exon 4, which results in abnormal mRNA (1). The second most common involves a deletion of 6.4 kb of DNA, including exon 1 through 5 and a portion of 6 in the gene (1). Other variants include frameshift and missense mutations in DNA sequences involving the MCOLN1 gene.

Although Uner Tan Syndrome is described as a collection of symptoms, the implications of the quadrupedal locomotion has caused it to receive the greatest amount of attention since its discovery. In 2008, Turkish scientists claimed to have found one of the genes responsible, at least in part, to this particular phenotype. Affected individuals in families A and D were homozygous for either deletions or nonsense mutations in the VLDLR gene on chromosome 9. This gene transcribes a very low-density

Heterozygous mutations in GLI3 on chromosome 7p14.1 have been associated with a rare life threatening disorder involving hypothalamic hamartoma, polydactyly, ARM, respiratory tract abnormalities called Pallister-Hall syndrome [40,42,53]. Townes-Brocks syndrome is an AD disorder characterized by ear, anal, limb, and renal malformations (REAR syndrome), results from mutations in the SALL1 gene [58].

Marshall’s Syndrome is a rare autosomal dominant genetic disorder. It causes distinctive facial features and limits hearing, smell, and sight based senses. It is caused by irregularities in the COL11A1 gene. Research on the disease is limited. The number of people affected by it is unknown due to little research on the subject. Though the disease causes many problems for the people affected by it, it’s not impossible to live a normal life while suffering from its effects.

The disorder is a syndrome that is found in newborns and children that consisted of osteoporosis with fractures and skeletal deformities (Mccance & Huether, 2014). Its classification is based on both inheritance and clinical findings. In the most severe form of this disorder, the child is usually stillborn or dies soon after birth, but some may survive into childhood. In its more severe forms the signs and symptoms are evident at birth because fractures and deformity have occurred in utero. The less severe forms may be evident until the child starts to walk. Clinical manifestations of this disease are osteoporosis and increased rate of fractures, possible bony deformation, triangular faces, possible vascular weakness, possible blue sclera, and poor dentition (McCance & Huether, 2014). The main errors in this disease is due to the synthesis of collagen, a triple helix that contains two matching alpha chains and one beta chain. Collagen is mostly present in bone, cartilage, eye tissue, skin, and the vascular system. The severity of this disorder phenotype along the related anomalies are primarily dependent on the severity of the genetic anomaly and the part of the triple helix that is affected (Greeley, et al., 2013). Moreover,