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Acromesomelic dysplasia

Acromesomelic dysplasia is a rare skeletal disorder that causes abnormal bone and cartilage development, leading to shortening of the forearms, lower legs, hands, feet, fingers, and toes.[2] Five different genetic mutations have been implicated in the disorder. Treatment is individualized but is generally aimed at palliating symptoms, for example, treatment of kyphosis and lumbar hyperlordosis.[3]

Acromesomelic dysplasia
Other namesAcromesomelic dwarfism [1]
SpecialtyOrthopedic

Signs and Symptoms edit

Acromesomelic dysplasia (AMD) is characterized by the inhibition of growth of certain long bones such as the forearms and lower legs.[4] This disease typically becomes apparent during the first years of life.[4] Forearms, lower legs, hands and feet do not grow proportionally with the rest of the body.[5] Over time, individuals can have a hard time fully extending their arms, rotating the arms inwards towards the body with palms facing down and rotating the arms outward with the palms facing upward.[5] Abnormalities of cartilage and bone development may also cause the bones within the fingers, toes, hands and feet to become sufficiently shorter and broader.[5] During early childhood, individuals may experience progressive, abnormal curvature of the spine.[5] Common symptoms include:

Infants with AMD typically have a normal birth weight, but can have other characteristic facial abnormalities.[4]

Causes edit

AMD is extremely rare and is inherited as an autosomal recessive genetic trait.[4] Autosomal recessive means that two copies of an abnormal gene must be present in order for the disease to develop.[6] This can be inherited from the parents or the gene can mutate in the person who has AMD.[4]

Pathophysiology edit

Genetic studies indicate that the mutation at chromosome 9p13-12, for AMD Maroteaux, is a gene that codes for a protein that affects bone development, natriuretic peptide receptor B (Npr2).[4][7] This is a receptor for the hormone C-type natriuretic peptide which is a hormone that is essential for bone growth.[4][7] AMD Grebe dysplasia has a gene located at chromosome 20q11.2 [4][8] This chromosome codes for a protein known as growth and development factor-5 (GDF5).[4][7] AMD with genital anomalies has a gene located at chromosome 4q23-24; this codes for a protein known as a bone morphogenetic protein receptor, type 1B.[4][9]Genetic diseases are determined by the combination of genes for a certain trait that is on the chromosomes received from the mother and father.[4]

Dominant genetic disorders happen when a single copy of an abnormal gene is needed to cause a certain disease.[4] The abnormal gene can be inherited from either parent or result from a gene mutation.[4]

Diagnosis edit

The diagnosis is based on a clinical presentation, molecular analysis, electropherogram and radiograph.[10][4] This disease is diagnosed within the first few years of life.[4] Identification of the main characteristics is the key factor in diagnosis. Molecular analysis is used to examine the DNA of the affected person and their parents.[10] For this, a blood sample is needed and the DNA will be extracted with an automatic DNA extractor.[10] The results will show the mutated chromosome and identify if this chromosome was passed on from a parent.[10] A radiograph will show abnormal growth plates and misshapen bones in the limbs.[7][3][10] This can confirm the abnormal development and premature fusion of the regions where the diaphyses, of certain long bones, meet their epiphyses.[4] Electropherogram is used to identify genotyping.[citation needed] These results can be used to compare to a normal sequence and relatives sequences.[11]

 
This is a radiograph of the left hand that shows the different types of joints. This scan can show the growth plate and the shape of each bone.

It is important to have a detailed patient history, including the parents or other relatives.[4] Typically, the parent that carries the chromosome for AMD, seems to be shorter than average.[7][12] Monitoring the weight and height of the person affected with AMD is important.[11] Based on the person's age, they should be meeting a certain percentile to identify any issues that may be causing a stunt in growth.[4]

There are five types of AMD:[4]

  1. Osebold-Remondini[13]
  2. Maroteaux[7]
  3. Grebe dysplasia[8]
  4. Du Pan syndrome[14]
  5. Acromesomelic dysplasia with genital anomalies[9]

Osebold-Remondini causes shortness of limbs and hypoplasia of the second phalanges with fusion to the remaining phalanges, carpal and tarsal coalitions.[13] Maroteaux type causes severe dwarfism with a height below 120 cm.[7] This type also causes shortening of the middle and distal segments of the limbs.[7] Grebe dysplasia causes extreme abnormalities of the limb joints and limbs.[8] In this type of AMD, the hands and feet are affected the most.[8] This type primarily affects the joints in the hands and feet causing a lack of articulation.[8] Grebe dysplasia does not have any major effects on the stature.[8] Du Pan syndrome causes underdevelopment of the tissues in the fibulae, feet and hands.[14] Acromesomelic dysplasia with genital anomalies causes shortness of limbs and stature with congenital malformations of the female genital tract and male reproductive system.[9]

All five types of AMD are caused by a gene mutation or receiving it from their parents.[4] The differences between the types are the different genes that are affected. The mutated gene for each type is listed in the pathophysiology section.[citation needed]

Treatment edit

There are a few treatment plans for AMD and each person's results vary. Depending on the type of AMD and the symptoms the person has, their therapy may differ.[4] Physical therapy is aimed to help specific symptoms.[4] For example, abnormal curvature of the spine may be treated by exercises, braces, casts and in severe cases, corrective surgery.[4] It is important to start physical therapy as early as possible to ensure that people with AMD can reach their full potential.[4]

One treatment that can help a person who is affected with AMD is recombinant human growth hormone (rhGH).[4][15][16][11] Recombinant human growth hormones are produced in the pituitary gland and can help spur growth in children and adolescents.[17] It is used in AMD patients to help muscle and bone growth.[15][16][11][17] This treatment is long-term and will not cure this disease, it will only help the patient grow a couple of centimeters.[16][15][11] A case study showed a growth velocity of 3.6-4.2 cm/year during this first year of treatment.[15] As well as height improving from 1.2 to 1.8 SD over 5 years of treatment.[15] Another case study was conducted that showed within a year, a patient had an increase of 7.0 cm/year.[16] With this treatment, it is important to start it during the puberty stage.[16][11] Some patients that have received this treatment, have seen no difference or increase in height.[11] There is no prevention with AMD and not many options for managing the symptoms.[citation needed]

Kyphosis is an excessive outward curvature of the spine resulting in a hunch back.[18] Treatment for this disease includes taking pain relievers and osteoporosis medications.[18] Medication for osteoporosis helps strengthen the bones to help prevent any spinal fractures.[18] Lumbar hyperlordosis is a condition that occurs when the lower back region experiences stress or extra weight.[citation needed] This causes the lower back to become arched and creates muscle spasms or pain.[citation needed] Treatment focuses on stretching the lower back, quads, hip flexors and strengthening the hamstrings, glutes and abdominal muscles.[citation needed] Braces may be used to help relieve some stress or pressure on the lower back.[citation needed]

Risk factors from taking rhGH include:[17]

  1. Nerve, muscle or joint pain
  2. Edema
  3. Carpal tunnel syndrome
  4. Numbness and tingling of the skin
  5. High cholesterol
  6. Increase the risk of diabetes

Other risk factors that increase the risk of having AMD include a family history of having this condition or a child born from parents who are close blood relatives.[19]

Prognosis edit

A person diagnosed with AMD will have a normal life expectancy.[20] With this disease, there are no chances of full recovery; it is something that the person will have for their entire life.[5] Abnormal cartilage and bone development can affect many bones in the body.[5] Long term effects include joint pain, arthritis, abnormal curvature of the spine and short stature of limbs and height.[4][5]

Epidemiology edit

The prevalence of AMD is <1/1000000.[21] Nearly ten million people in the world carry the NPR2 mutated gene (Maroteaux type); only 3500 people in the entire world are affected with AMD.[20] AMD is rare and there are less than 100 reported cases.[19] AMD can be classified as skeletal dysplasia, which approximately occurs in 1 out of 5000 births.[22] This disease affects both males and females as well as any racial or ethnic group.[19] The majority of the case studies involve patients that live in Pakistan, Morocco, or Karnataka.[11][10][23][24] AMD does primarily begin in the first few years of life or as early as the neonatal phase, but it can affect anyone at any age.[4][19]

Current Research edit

A research study was published in 2022 that established a new type of AMD. In the case study, an exome sequence was performed on two girls that had short stature due to acromesomelic limb shortening.[25] The researchers wanted to determine if protein kinase cGMP-dependent type II gene (PRKG2) had any effect on longitudinal growth in bones.[25] The results showed two homozygous PRKG2 variants: nonsense and a frameshift.[25] These variants alter the downstream mitogen activated protein kinase signaling pathway by failing to phosphorylate c-Raf 1 at Ser43 and reduce activation in response to fibroblast growth factor 2.[25]

Another research study was conducted on mice to find a new treatment for people with AMD (Maroteaux type).[22] The results showed that Npr2 is expressed in osteoblasts and chondrocytes; leading to the conclusion that the disruptions in the growth plate from Npr2, can be a leading cause for AMD.[22] They also found that Npr2 stops the activation of a signaling pathway for MEK/ERK, which is a pathway in the growth plates.[22] The data showed that treatment of a pharmacological inhibitor of MEK/ERK pathway might improve bone growth.[22] The data for this treatment produced promising results. It showed that the drug effectively inhibited MEK/ERK activation.[22] This study was only conducted on mice, but it could potentially be a treatment to help people diagnosed with AMD.[citation needed]

There are research studies being conducted to see the effect of rhGH. As stated in the treatment section, results may vary per person. Some patients seem to have an overall positive effect of these hormones and it helps them grow a few more centimeters each year. No other clinical trials are going on for AMD. There is a lack of knowledge or medication that can treat or reverse this disease.[citation needed]

Notable cases edit

References edit

  1. ^ . rarediseases.info.nih.gov. Archived from the original on 11 October 2020. Retrieved 14 March 2019.
  2. ^ Nyberg, David A, ed. (2003). Diagnostic imaging of fetal anomalies (2nd ed.). Philadelphia, Pa. [u.a.]: Lippincott Williams & Wilkins. p. 683. ISBN 9780781732116.
  3. ^ a b "Acromesomelic Dysplasia - NORD (National Organization for Rare Disorders)". Retrieved 2015-09-19.
  4. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa "Acromesomelic Dysplasia". NORD (National Organization for Rare Disorders). Retrieved 2020-10-22.
  5. ^ a b c d e f g "Acromesomelic dysplasia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2020-10-22.
  6. ^ "Autosomal recessive: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2020-11-23.
  7. ^ a b c d e f g h "OMIM Entry - # 602875 - ACROMESOMELIC DYSPLASIA, MAROTEAUX TYPE; AMDM". www.omim.org. Retrieved 2020-11-09.
  8. ^ a b c d e f "OMIM Entry - # 200700 - CHONDRODYSPLASIA, GREBE TYPE". www.omim.org. Retrieved 2020-11-09.
  9. ^ a b c "OMIM Entry - # 609441 - ACROMESOMELIC DYSPLASIA, DEMIRHAN TYPE; AMDD". www.omim.org. Retrieved 2020-11-09.
  10. ^ a b c d e f Martinez-Garcia, Monica; Garcia-Canto, Eva; Fenollar-Cortes, Maria; Aytes, Antonio Perez; Trujillo-Tiebas, María José (September 2016). "Characterization of an acromesomelic dysplasia, Grebe type case: novel mutation affecting the recognition motif at the processing site of GDF5". Journal of Bone and Mineral Metabolism. 34 (5): 599–603. doi:10.1007/s00774-015-0693-z. PMID 26275437. S2CID 39776096.
  11. ^ a b c d e f g h Arya, Ved Bhushan; Raj, Meena; Younes, Maha; Chapman, Simon; Irving, Melita; Kapoor, Ritika R.; Buchanan, Charles R. (2020). "Acromesomelic Dysplasia, Type Maroteaux: Impact of Long-Term (8 Years) High-Dose Growth Hormone Treatment on Growth Velocity and Final Height in 2 Siblings". Hormone Research in Paediatrics. 93 (5): 335–342. doi:10.1159/000511874. PMID 33238275. S2CID 212958416.
  12. ^ Srivastava, Priyanka; Tuteja, Moni; Dalal, Ashwin; Mandal, Kausik; Phadke, Shubha R. (December 2016). "Novel mutations in the transmembrane natriuretic peptide receptor NPR-B gene in four Indian families with acromesomelic dysplasia, type Maroteaux". Journal of Genetics. 95 (4): 905–909. doi:10.1007/s12041-016-0715-1. PMID 27994189. S2CID 9000832.
  13. ^ a b "OMIM Entry - 112910 - OSEBOLD-REMONDINI SYNDROME". www.omim.org. Retrieved 2020-11-09.
  14. ^ a b "OMIM Entry - # 228900 - DU PAN SYNDROME; DUPANS". www.omim.org. Retrieved 2020-11-09.
  15. ^ a b c d e Plachy, Lukas; Dusatkova, Petra; Maratova, Klara; Petruzelkova, Lenka; Zemkova, Dana; Elblova, Lenka; Kucerova, Petra; Toni, Ledjona; Kolouskova, Stanislava; Snajderova, Marta; Sumnik, Zdenek; Lebl, Jan; Pruhova, Stepanka (March 2020). "NPR2 Variants Are Frequent among Children with Familiar Short Stature and Respond Well to Growth Hormone Therapy". The Journal of Clinical Endocrinology & Metabolism. 105 (3): e746–e752. doi:10.1210/clinem/dgaa037. PMID 31990356. S2CID 210935249.
  16. ^ a b c d e Vasques, Gabriela A.; Hisado-Oliva, Alfonso; Funari, Mariana F.A.; Lerario, Antonio M.; Quedas, Elisangela P.S.; Solberg, Paulo; Heath, Karen E.; Jorge, Alexander A.L. (2017). "Long-term response to growth hormone therapy in a patient with short stature caused by a novel heterozygous mutation in NPR2". Journal of Pediatric Endocrinology and Metabolism. 30 (1): 111–116. doi:10.1515/jpem-2016-0280. PMID 27941173. S2CID 13272645. ProQuest 1863286437.
  17. ^ a b c "HGH (Human Growth Hormone): Uses and Side Effects". WebMD. Retrieved 2020-11-10.
  18. ^ a b c "Kyphosis - Symptoms and causes". Mayo Clinic. Retrieved 2020-11-23.
  19. ^ a b c d Tangella, Krish (December 15, 2019). "Acromesomelic Dysplasia". www.dovemed.com. Retrieved 2020-11-10.
  20. ^ a b "Acromesomelic Dysplasia | Boston Children's Hospital". www.childrenshospital.org. Retrieved 2020-11-10.
  21. ^ "Orphanet: Acromesomelic dwarfism". www.orpha.net. Retrieved 2020-11-10.
  22. ^ a b c d e f Geister, Krista (12 October 2012). "A novel loss-of-function mutation in Npr2 clarifies primary role in female reproduction and reveals a potential therapy for acromesomelic dysplasia, Maroteaux type". Human Molecular Genetics. 22 (2): 345–57. doi:10.1093/hmg/dds432. PMC 4817088. PMID 23065701.
  23. ^ Stange, Katja; Désir, Julie; Kakar, Naseebullah; Mueller, Thomas D.; Budde, Birgit S.; Gordon, Christopher T.; Horn, Denise; Seemann, Petra; Borck, Guntram (December 2015). "A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia". Orphanet Journal of Rare Diseases. 10 (1): 84. doi:10.1186/s13023-015-0299-5. PMC 4482310. PMID 26105076.
  24. ^ Ullah, Asmat; Umair, Muhammad; Muhammad, Dost; Bilal, Muhammad; Lee, Kwanghyuk; Leal, Suzanne M; Ahmad, Wasim (May 2018). "A novel homozygous variant in BMPR1B underlies acromesomelic dysplasia Hunter–Thompson type". Annals of Human Genetics. 82 (3): 129–134. doi:10.1111/ahg.12233. PMC 6141004. PMID 29322508.
  25. ^ a b c d Díaz-González, Francisca; Wadhwa, Saruchi; Rodriguez-Zabala, Maria; Kumar, Somesh; Aza-Carmona, Miriam; Sentchordi-Montané, Lucia; Alonso, Milagros; Ahmad, Istaq; Zahra, Sana; Kumar, Deepak; Kushwah, Neetu; Shamim, Uzma; Sait, Haseena; Kapoor, Seema; Roldán, Belen; Nishimura, Gen; Offiah, Amaka C; Faruq, Mohammed; Heath, Karen E. (January 2022). "Biallelic cGMP-dependent type II protein kinase gene ( PRKG2 ) variants cause a novel acromesomelic dysplasia". Journal of Medical Genetics. 59 (1): 28–38. doi:10.1136/jmedgenet-2020-107177. PMID 33106379. S2CID 225069126.
  26. ^ "Patrons". Skeletal Dysplasia Group. Retrieved 25 June 2023.

External links edit

acromesomelic, dysplasia, rare, skeletal, disorder, that, causes, abnormal, bone, cartilage, development, leading, shortening, forearms, lower, legs, hands, feet, fingers, toes, five, different, genetic, mutations, have, been, implicated, disorder, treatment, . Acromesomelic dysplasia is a rare skeletal disorder that causes abnormal bone and cartilage development leading to shortening of the forearms lower legs hands feet fingers and toes 2 Five different genetic mutations have been implicated in the disorder Treatment is individualized but is generally aimed at palliating symptoms for example treatment of kyphosis and lumbar hyperlordosis 3 Acromesomelic dysplasiaOther namesAcromesomelic dwarfism 1 SpecialtyOrthopedic Contents 1 Signs and Symptoms 2 Causes 2 1 Pathophysiology 3 Diagnosis 4 Treatment 5 Prognosis 6 Epidemiology 7 Current Research 8 Notable cases 9 References 10 External linksSigns and Symptoms editAcromesomelic dysplasia AMD is characterized by the inhibition of growth of certain long bones such as the forearms and lower legs 4 This disease typically becomes apparent during the first years of life 4 Forearms lower legs hands and feet do not grow proportionally with the rest of the body 5 Over time individuals can have a hard time fully extending their arms rotating the arms inwards towards the body with palms facing down and rotating the arms outward with the palms facing upward 5 Abnormalities of cartilage and bone development may also cause the bones within the fingers toes hands and feet to become sufficiently shorter and broader 5 During early childhood individuals may experience progressive abnormal curvature of the spine 5 Common symptoms include Short stature Progressive degeneration Stiffness Tenderness Osteoarthritis Abnormal bone shapeInfants with AMD typically have a normal birth weight but can have other characteristic facial abnormalities 4 Macrocephaly Frontal bossing Occipital prominence Slightly flattened midface Abnormally small pug noseCauses editAMD is extremely rare and is inherited as an autosomal recessive genetic trait 4 Autosomal recessive means that two copies of an abnormal gene must be present in order for the disease to develop 6 This can be inherited from the parents or the gene can mutate in the person who has AMD 4 Pathophysiology edit Genetic studies indicate that the mutation at chromosome 9p13 12 for AMD Maroteaux is a gene that codes for a protein that affects bone development natriuretic peptide receptor B Npr2 4 7 This is a receptor for the hormone C type natriuretic peptide which is a hormone that is essential for bone growth 4 7 AMD Grebe dysplasia has a gene located at chromosome 20q11 2 4 8 This chromosome codes for a protein known as growth and development factor 5 GDF5 4 7 AMD with genital anomalies has a gene located at chromosome 4q23 24 this codes for a protein known as a bone morphogenetic protein receptor type 1B 4 9 Genetic diseases are determined by the combination of genes for a certain trait that is on the chromosomes received from the mother and father 4 Dominant genetic disorders happen when a single copy of an abnormal gene is needed to cause a certain disease 4 The abnormal gene can be inherited from either parent or result from a gene mutation 4 Diagnosis editThe diagnosis is based on a clinical presentation molecular analysis electropherogram and radiograph 10 4 This disease is diagnosed within the first few years of life 4 Identification of the main characteristics is the key factor in diagnosis Molecular analysis is used to examine the DNA of the affected person and their parents 10 For this a blood sample is needed and the DNA will be extracted with an automatic DNA extractor 10 The results will show the mutated chromosome and identify if this chromosome was passed on from a parent 10 A radiograph will show abnormal growth plates and misshapen bones in the limbs 7 3 10 This can confirm the abnormal development and premature fusion of the regions where the diaphyses of certain long bones meet their epiphyses 4 Electropherogram is used to identify genotyping citation needed These results can be used to compare to a normal sequence and relatives sequences 11 nbsp This is a radiograph of the left hand that shows the different types of joints This scan can show the growth plate and the shape of each bone It is important to have a detailed patient history including the parents or other relatives 4 Typically the parent that carries the chromosome for AMD seems to be shorter than average 7 12 Monitoring the weight and height of the person affected with AMD is important 11 Based on the person s age they should be meeting a certain percentile to identify any issues that may be causing a stunt in growth 4 There are five types of AMD 4 Osebold Remondini 13 Maroteaux 7 Grebe dysplasia 8 Du Pan syndrome 14 Acromesomelic dysplasia with genital anomalies 9 Osebold Remondini causes shortness of limbs and hypoplasia of the second phalanges with fusion to the remaining phalanges carpal and tarsal coalitions 13 Maroteaux type causes severe dwarfism with a height below 120 cm 7 This type also causes shortening of the middle and distal segments of the limbs 7 Grebe dysplasia causes extreme abnormalities of the limb joints and limbs 8 In this type of AMD the hands and feet are affected the most 8 This type primarily affects the joints in the hands and feet causing a lack of articulation 8 Grebe dysplasia does not have any major effects on the stature 8 Du Pan syndrome causes underdevelopment of the tissues in the fibulae feet and hands 14 Acromesomelic dysplasia with genital anomalies causes shortness of limbs and stature with congenital malformations of the female genital tract and male reproductive system 9 All five types of AMD are caused by a gene mutation or receiving it from their parents 4 The differences between the types are the different genes that are affected The mutated gene for each type is listed in the pathophysiology section citation needed Treatment editThere are a few treatment plans for AMD and each person s results vary Depending on the type of AMD and the symptoms the person has their therapy may differ 4 Physical therapy is aimed to help specific symptoms 4 For example abnormal curvature of the spine may be treated by exercises braces casts and in severe cases corrective surgery 4 It is important to start physical therapy as early as possible to ensure that people with AMD can reach their full potential 4 One treatment that can help a person who is affected with AMD is recombinant human growth hormone rhGH 4 15 16 11 Recombinant human growth hormones are produced in the pituitary gland and can help spur growth in children and adolescents 17 It is used in AMD patients to help muscle and bone growth 15 16 11 17 This treatment is long term and will not cure this disease it will only help the patient grow a couple of centimeters 16 15 11 A case study showed a growth velocity of 3 6 4 2 cm year during this first year of treatment 15 As well as height improving from 1 2 to 1 8 SD over 5 years of treatment 15 Another case study was conducted that showed within a year a patient had an increase of 7 0 cm year 16 With this treatment it is important to start it during the puberty stage 16 11 Some patients that have received this treatment have seen no difference or increase in height 11 There is no prevention with AMD and not many options for managing the symptoms citation needed Kyphosis is an excessive outward curvature of the spine resulting in a hunch back 18 Treatment for this disease includes taking pain relievers and osteoporosis medications 18 Medication for osteoporosis helps strengthen the bones to help prevent any spinal fractures 18 Lumbar hyperlordosis is a condition that occurs when the lower back region experiences stress or extra weight citation needed This causes the lower back to become arched and creates muscle spasms or pain citation needed Treatment focuses on stretching the lower back quads hip flexors and strengthening the hamstrings glutes and abdominal muscles citation needed Braces may be used to help relieve some stress or pressure on the lower back citation needed Risk factors from taking rhGH include 17 Nerve muscle or joint pain Edema Carpal tunnel syndrome Numbness and tingling of the skin High cholesterol Increase the risk of diabetesOther risk factors that increase the risk of having AMD include a family history of having this condition or a child born from parents who are close blood relatives 19 Prognosis editA person diagnosed with AMD will have a normal life expectancy 20 With this disease there are no chances of full recovery it is something that the person will have for their entire life 5 Abnormal cartilage and bone development can affect many bones in the body 5 Long term effects include joint pain arthritis abnormal curvature of the spine and short stature of limbs and height 4 5 Epidemiology editThe prevalence of AMD is lt 1 1000000 21 Nearly ten million people in the world carry the NPR2 mutated gene Maroteaux type only 3500 people in the entire world are affected with AMD 20 AMD is rare and there are less than 100 reported cases 19 AMD can be classified as skeletal dysplasia which approximately occurs in 1 out of 5000 births 22 This disease affects both males and females as well as any racial or ethnic group 19 The majority of the case studies involve patients that live in Pakistan Morocco or Karnataka 11 10 23 24 AMD does primarily begin in the first few years of life or as early as the neonatal phase but it can affect anyone at any age 4 19 Current Research editA research study was published in 2022 that established a new type of AMD In the case study an exome sequence was performed on two girls that had short stature due to acromesomelic limb shortening 25 The researchers wanted to determine if protein kinase cGMP dependent type II gene PRKG2 had any effect on longitudinal growth in bones 25 The results showed two homozygous PRKG2 variants nonsense and a frameshift 25 These variants alter the downstream mitogen activated protein kinase signaling pathway by failing to phosphorylate c Raf 1 at Ser43 and reduce activation in response to fibroblast growth factor 2 25 Another research study was conducted on mice to find a new treatment for people with AMD Maroteaux type 22 The results showed that Npr2 is expressed in osteoblasts and chondrocytes leading to the conclusion that the disruptions in the growth plate from Npr2 can be a leading cause for AMD 22 They also found that Npr2 stops the activation of a signaling pathway for MEK ERK which is a pathway in the growth plates 22 The data showed that treatment of a pharmacological inhibitor of MEK ERK pathway might improve bone growth 22 The data for this treatment produced promising results It showed that the drug effectively inhibited MEK ERK activation 22 This study was only conducted on mice but it could potentially be a treatment to help people diagnosed with AMD citation needed There are research studies being conducted to see the effect of rhGH As stated in the treatment section results may vary per person Some patients seem to have an overall positive effect of these hormones and it helps them grow a few more centimeters each year No other clinical trials are going on for AMD There is a lack of knowledge or medication that can treat or reverse this disease citation needed Notable cases editKiruna Stamell British Australian actor 26 References edit Acromesomelic dysplasia Genetic and Rare Diseases Information Center GARD an NCATS Program rarediseases info nih gov Archived from the original on 11 October 2020 Retrieved 14 March 2019 Nyberg David A ed 2003 Diagnostic imaging of fetal anomalies 2nd ed Philadelphia Pa u a Lippincott Williams amp Wilkins p 683 ISBN 9780781732116 a b Acromesomelic Dysplasia NORD National Organization for Rare Disorders Retrieved 2015 09 19 a b c d e f g h i j k l m n o p q r s t u v w x y z aa Acromesomelic Dysplasia NORD National Organization for Rare Disorders Retrieved 2020 10 22 a b c d e f g Acromesomelic dysplasia Genetic and Rare Diseases Information Center GARD an NCATS Program rarediseases info nih gov Retrieved 2020 10 22 Autosomal recessive MedlinePlus Medical Encyclopedia medlineplus gov Retrieved 2020 11 23 a b c d e f g h OMIM Entry 602875 ACROMESOMELIC DYSPLASIA MAROTEAUX TYPE AMDM www omim org Retrieved 2020 11 09 a b c d e f OMIM Entry 200700 CHONDRODYSPLASIA GREBE TYPE www omim org Retrieved 2020 11 09 a b c OMIM Entry 609441 ACROMESOMELIC DYSPLASIA DEMIRHAN TYPE AMDD www omim org Retrieved 2020 11 09 a b c d e f Martinez Garcia Monica Garcia Canto Eva Fenollar Cortes Maria Aytes Antonio Perez Trujillo Tiebas Maria Jose September 2016 Characterization of an acromesomelic dysplasia Grebe type case novel mutation affecting the recognition motif at the processing site of GDF5 Journal of Bone and Mineral Metabolism 34 5 599 603 doi 10 1007 s00774 015 0693 z PMID 26275437 S2CID 39776096 a b c d e f g h Arya Ved Bhushan Raj Meena Younes Maha Chapman Simon Irving Melita Kapoor Ritika R Buchanan Charles R 2020 Acromesomelic Dysplasia Type Maroteaux Impact of Long Term 8 Years High Dose Growth Hormone Treatment on Growth Velocity and Final Height in 2 Siblings Hormone Research in Paediatrics 93 5 335 342 doi 10 1159 000511874 PMID 33238275 S2CID 212958416 Srivastava Priyanka Tuteja Moni Dalal Ashwin Mandal Kausik Phadke Shubha R December 2016 Novel mutations in the transmembrane natriuretic peptide receptor NPR B gene in four Indian families with acromesomelic dysplasia type Maroteaux Journal of Genetics 95 4 905 909 doi 10 1007 s12041 016 0715 1 PMID 27994189 S2CID 9000832 a b OMIM Entry 112910 OSEBOLD REMONDINI SYNDROME www omim org Retrieved 2020 11 09 a b OMIM Entry 228900 DU PAN SYNDROME DUPANS www omim org Retrieved 2020 11 09 a b c d e Plachy Lukas Dusatkova Petra Maratova Klara Petruzelkova Lenka Zemkova Dana Elblova Lenka Kucerova Petra Toni Ledjona Kolouskova Stanislava Snajderova Marta Sumnik Zdenek Lebl Jan Pruhova Stepanka March 2020 NPR2 Variants Are Frequent among Children with Familiar Short Stature and Respond Well to Growth Hormone Therapy The Journal of Clinical Endocrinology amp Metabolism 105 3 e746 e752 doi 10 1210 clinem dgaa037 PMID 31990356 S2CID 210935249 a b c d e Vasques Gabriela A Hisado Oliva Alfonso Funari Mariana F A Lerario Antonio M Quedas Elisangela P S Solberg Paulo Heath Karen E Jorge Alexander A L 2017 Long term response to growth hormone therapy in a patient with short stature caused by a novel heterozygous mutation in NPR2 Journal of Pediatric Endocrinology and Metabolism 30 1 111 116 doi 10 1515 jpem 2016 0280 PMID 27941173 S2CID 13272645 ProQuest 1863286437 a b c HGH Human Growth Hormone Uses and Side Effects WebMD Retrieved 2020 11 10 a b c Kyphosis Symptoms and causes Mayo Clinic Retrieved 2020 11 23 a b c d Tangella Krish December 15 2019 Acromesomelic Dysplasia www dovemed com Retrieved 2020 11 10 a b Acromesomelic Dysplasia Boston Children s Hospital www childrenshospital org Retrieved 2020 11 10 Orphanet Acromesomelic dwarfism www orpha net Retrieved 2020 11 10 a b c d e f Geister Krista 12 October 2012 A novel loss of function mutation in Npr2 clarifies primary role in female reproduction and reveals a potential therapy for acromesomelic dysplasia Maroteaux type Human Molecular Genetics 22 2 345 57 doi 10 1093 hmg dds432 PMC 4817088 PMID 23065701 Stange Katja Desir Julie Kakar Naseebullah Mueller Thomas D Budde Birgit S Gordon Christopher T Horn Denise Seemann Petra Borck Guntram December 2015 A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia Orphanet Journal of Rare Diseases 10 1 84 doi 10 1186 s13023 015 0299 5 PMC 4482310 PMID 26105076 Ullah Asmat Umair Muhammad Muhammad Dost Bilal Muhammad Lee Kwanghyuk Leal Suzanne M Ahmad Wasim May 2018 A novel homozygous variant in BMPR1B underlies acromesomelic dysplasia Hunter Thompson type Annals of Human Genetics 82 3 129 134 doi 10 1111 ahg 12233 PMC 6141004 PMID 29322508 a b c d Diaz Gonzalez Francisca Wadhwa Saruchi Rodriguez Zabala Maria Kumar Somesh Aza Carmona Miriam Sentchordi Montane Lucia Alonso Milagros Ahmad Istaq Zahra Sana Kumar Deepak Kushwah Neetu Shamim Uzma Sait Haseena Kapoor Seema Roldan Belen Nishimura Gen Offiah Amaka C Faruq Mohammed Heath Karen E January 2022 Biallelic cGMP dependent type II protein kinase gene PRKG2 variants cause a novel acromesomelic dysplasia Journal of Medical Genetics 59 1 28 38 doi 10 1136 jmedgenet 2020 107177 PMID 33106379 S2CID 225069126 Patrons Skeletal Dysplasia Group Retrieved 25 June 2023 External links edit Retrieved from https en wikipedia org w index php title Acromesomelic dysplasia amp oldid 1167183307, wikipedia, wiki, book, books, library,

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