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Acrodysostosis 2 with or without hormone resistance(ACRDYS2)

MedGen UID:
766164
Concept ID:
C3553250
Disease or Syndrome
Synonyms: ACRODYSOSTOSIS 2 WITH HORMONE RESISTANCE; ACRODYSOSTOSIS 2 WITHOUT HORMONE RESISTANCE
 
Gene (location): PDE4D (5q11.2-12.1)
 
Monarch Initiative: MONDO:0013822
OMIM®: 614613

Definition

Acrodysostosis-2 (ACRDYS2) is a rare skeletal dysplasia characterized by brachydactyly, facial dysostosis, and spinal stenosis. Many patients have intellectual disability and some have hormone resistance (summary by Michot et al., 2012 and Lee et al., 2012). For a discussion of genetic heterogeneity of acrodysostosis, see ACRDYS1 (101800). [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Short phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Short metatarsal
MedGen UID:
341358
Concept ID:
C1849020
Finding
Diminished length of a metatarsal bone, with resultant proximal displacement of the associated toe.
Advanced ossification of carpal bones
MedGen UID:
341422
Concept ID:
C1849292
Finding
Ossification of carpal bones at an abnormally early age.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Mild short stature
MedGen UID:
461427
Concept ID:
C3150077
Finding
A mild degree of short stature, more than -2 SD but not more than -3 SD from mean corrected for age and sex.
Autism
MedGen UID:
13966
Concept ID:
C0004352
Mental or Behavioral Dysfunction
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; AUTS19 (615091), associated with mutation in the EIF4E gene (133440) on chromosome 4q23; and AUTS20 (618830), associated with mutation in the NLGN1 gene (600568) on chromosome 3q26. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.
Increased intracranial pressure
MedGen UID:
56241
Concept ID:
C0151740
Finding
An increase of the pressure inside the cranium (skull) and thereby in the brain tissue and cerebrospinal fluid.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Spinal canal stenosis
MedGen UID:
396107
Concept ID:
C1861329
Anatomical Abnormality
An abnormal narrowing of the spinal canal.
Cone-shaped epiphysis
MedGen UID:
351282
Concept ID:
C1865037
Finding
Cone-shaped epiphyses (also known as coned epiphyses) are epiphyses that invaginate into cupped metaphyses. That is, the epiphysis has a cone-shaped distal extension resulting from increased growth of the central portion of the epiphysis relative to its periphery.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Round face
MedGen UID:
116087
Concept ID:
C0239479
Finding
The facial appearance is more circular than usual as viewed from the front.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Red hair
MedGen UID:
66796
Concept ID:
C0239803
Finding
Fair hair
MedGen UID:
336542
Concept ID:
C1849221
Finding
A lesser degree of hair pigmentation than would otherwise be expected.
Congenital hypothyroidism
MedGen UID:
41344
Concept ID:
C0010308
Disease or Syndrome
Congenital hypothyroidism is a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital). The thyroid gland is a butterfly-shaped tissue in the lower neck. It makes iodine-containing hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). People with congenital hypothyroidism have lower-than-normal levels of these important hormones.\n\nSigns and symptoms of congenital hypothyroidism result from the shortage of thyroid hormones. Affected babies may show no features of the condition, although some babies with congenital hypothyroidism are less active and sleep more than normal. They may have difficulty feeding and experience constipation. If untreated, congenital hypothyroidism can lead to intellectual disability and slow growth. In the United States and many other countries, all hospitals test newborns for congenital hypothyroidism. If treatment begins in the first two weeks after birth, infants usually develop normally.\n\nCongenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. In 80 to 85 percent of cases, the thyroid gland is absent, severely reduced in size (hypoplastic), or abnormally located. These cases are classified as thyroid dysgenesis. In the remainder of cases, a normal-sized or enlarged thyroid gland (goiter) is present, but production of thyroid hormones is decreased or absent. Most of these cases occur when one of several steps in the hormone synthesis process is impaired; these cases are classified as thyroid dyshormonogenesis. Less commonly, reduction or absence of thyroid hormone production is caused by impaired stimulation of the production process (which is normally done by a structure at the base of the brain called the pituitary gland), even though the process itself is unimpaired. These cases are classified as central (or pituitary) hypothyroidism.\n\nCongenital hypothyroidism can also occur as part of syndromes that affect other organs and tissues in the body. These forms of the condition are described as syndromic. Some common forms of syndromic hypothyroidism include Pendred syndrome, Bamforth-Lazarus syndrome, and brain-lung-thyroid syndrome.
Blue irides
MedGen UID:
108297
Concept ID:
C0578626
Finding
A markedly blue coloration of the iris.

Professional guidelines

PubMed

Riemann D, Espie CA, Altena E, Arnardottir ES, Baglioni C, Bassetti CLA, Bastien C, Berzina N, Bjorvatn B, Dikeos D, Dolenc Groselj L, Ellis JG, Garcia-Borreguero D, Geoffroy PA, Gjerstad M, Gonçalves M, Hertenstein E, Hoedlmoser K, Hion T, Holzinger B, Janku K, Jansson-Fröjmark M, Järnefelt H, Jernelöv S, Jennum PJ, Khachatryan S, Krone L, Kyle SD, Lancee J, Leger D, Lupusor A, Marques DR, Nissen C, Palagini L, Paunio T, Perogamvros L, Pevernagie D, Schabus M, Shochat T, Szentkiralyi A, Van Someren E, van Straten A, Wichniak A, Verbraecken J, Spiegelhalder K
J Sleep Res 2023 Dec;32(6):e14035. doi: 10.1111/jsr.14035. PMID: 38016484
Cho MR, Lee S, Song SK
J Korean Med Sci 2022 May 9;37(18):e146. doi: 10.3346/jkms.2022.37.e146. PMID: 35535373Free PMC Article
Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Gonçalves M, Hertenstein E, Jansson-Fröjmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weeß HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K
J Sleep Res 2017 Dec;26(6):675-700. Epub 2017 Sep 5 doi: 10.1111/jsr.12594. PMID: 28875581

Recent clinical studies

Etiology

Pataky MW, Dasari S, Michie KL, Sevits KJ, Kumar AA, Klaus KA, Heppelmann CJ, Robinson MM, Carter RE, Lanza IR, Nair KS
Cell Metab 2023 Nov 7;35(11):1996-2010.e6. doi: 10.1016/j.cmet.2023.10.010. PMID: 37939659Free PMC Article
Zhang T, He Q, Xiu H, Zhang Z, Liu Y, Chen Z, Hu H
Reprod Sci 2023 Apr;30(4):1033-1048. Epub 2022 Aug 8 doi: 10.1007/s43032-022-01038-2. PMID: 35941510
Zhang H, Wang W, Zhao J, Jiao P, Zeng L, Zhang H, Zhao Y, Shi L, Hu H, Luo L, Fukuzawa I, Li D, Li R, Qiao J
Front Endocrinol (Lausanne) 2022;13:1085656. Epub 2023 Jan 9 doi: 10.3389/fendo.2022.1085656. PMID: 36699018Free PMC Article
Drăgănescu M, Carmocan C
Chirurgia (Bucur) 2017 Jul-Aug;112(4):413-417. doi: 10.21614/chirurgia.112.4.413. PMID: 28862117
Morton RW, Oikawa SY, Wavell CG, Mazara N, McGlory C, Quadrilatero J, Baechler BL, Baker SK, Phillips SM
J Appl Physiol (1985) 2016 Jul 1;121(1):129-38. Epub 2016 May 12 doi: 10.1152/japplphysiol.00154.2016. PMID: 27174923Free PMC Article

Diagnosis

Yang J, Chen C
J Endocrinol 2024 Apr 1;261(1) Epub 2024 Feb 15 doi: 10.1530/JOE-23-0342. PMID: 38285626
Zhang H, Wang W, Zhao J, Jiao P, Zeng L, Zhang H, Zhao Y, Shi L, Hu H, Luo L, Fukuzawa I, Li D, Li R, Qiao J
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Mantovani G, Bastepe M, Monk D, de Sanctis L, Thiele S, Ahmed SF, Bufo R, Choplin T, De Filippo G, Devernois G, Eggermann T, Elli FM, Garcia Ramirez A, Germain-Lee EL, Groussin L, Hamdy NAT, Hanna P, Hiort O, Jüppner H, Kamenický P, Knight N, Le Norcy E, Lecumberri B, Levine MA, Mäkitie O, Martin R, Martos-Moreno GÁ, Minagawa M, Murray P, Pereda A, Pignolo R, Rejnmark L, Rodado R, Rothenbuhler A, Saraff V, Shoemaker AH, Shore EM, Silve C, Turan S, Woods P, Zillikens MC, Perez de Nanclares G, Linglart A
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Kraemer WJ, Ratamess NA, Hymer WC, Nindl BC, Fragala MS
Front Endocrinol (Lausanne) 2020;11:33. Epub 2020 Feb 25 doi: 10.3389/fendo.2020.00033. PMID: 32158429Free PMC Article
Cheng SY, Leonard JL, Davis PJ
Endocr Rev 2010 Apr;31(2):139-70. Epub 2010 Jan 5 doi: 10.1210/er.2009-0007. PMID: 20051527Free PMC Article

Therapy

Newsome PN, Ambery P
J Hepatol 2023 Dec;79(6):1557-1565. Epub 2023 Aug 9 doi: 10.1016/j.jhep.2023.07.033. PMID: 37562748
Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, Park S, Hegyi P, Nyirády P, Ács N, Várbíró S, Horváth EM
Reprod Biol Endocrinol 2023 Jan 26;21(1):10. doi: 10.1186/s12958-023-01055-z. PMID: 36703143Free PMC Article
Laurindo LF, Barbalho SM, Guiguer EL, da Silva Soares de Souza M, de Souza GA, Fidalgo TM, Araújo AC, de Souza Gonzaga HF, de Bortoli Teixeira D, de Oliveira Silva Ullmann T, Sloan KP, Sloan LA
Int J Mol Sci 2022 Jan 10;23(2) doi: 10.3390/ijms23020739. PMID: 35054924Free PMC Article
Drăgănescu M, Carmocan C
Chirurgia (Bucur) 2017 Jul-Aug;112(4):413-417. doi: 10.21614/chirurgia.112.4.413. PMID: 28862117
Baggio LL, Drucker DJ
Gastroenterology 2007 May;132(6):2131-57. doi: 10.1053/j.gastro.2007.03.054. PMID: 17498508

Prognosis

Sakkat A, Cox G, Khalidi N, Larche M, Beattie K, Renzoni EA, Morar N, Kouranos V, Kolb M, Hambly N
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Bardia A, Aftimos P, Bihani T, Anderson-Villaluz AT, Jung J, Conlan MG, Kaklamani VG
Future Oncol 2019 Oct;15(28):3209-3218. Epub 2019 Aug 20 doi: 10.2217/fon-2019-0370. PMID: 31426673
Laclaustra M, Moreno-Franco B, Lou-Bonafonte JM, Mateo-Gallego R, Casasnovas JA, Guallar-Castillon P, Cenarro A, Civeira F
Diabetes Care 2019 Feb;42(2):303-310. Epub 2018 Dec 14 doi: 10.2337/dc18-1410. PMID: 30552134
Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE; COU-AA-302 Investigators
Lancet Oncol 2015 Feb;16(2):152-60. Epub 2015 Jan 16 doi: 10.1016/S1470-2045(14)71205-7. PMID: 25601341
Tsigos C, Chrousos GP
J Psychosom Res 2002 Oct;53(4):865-71. doi: 10.1016/s0022-3999(02)00429-4. PMID: 12377295

Clinical prediction guides

Pustotina O, Myers SH, Unfer V, Rasulova I
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D'Souza AC, Wageh M, Williams JS, Colenso-Semple LM, McCarthy DG, McKay AKA, Elliott-Sale KJ, Burke LM, Parise G, MacDonald MJ, Tarnopolsky MA, Phillips SM
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Expert Rev Cardiovasc Ther 2011 Jun;9(6):711-20. doi: 10.1586/erc.11.25. PMID: 21714602
Tsigos C, Chrousos GP
J Psychosom Res 2002 Oct;53(4):865-71. doi: 10.1016/s0022-3999(02)00429-4. PMID: 12377295
Weinmann M
Crit Care Clin 2001 Jan;17(1):1-10. doi: 10.1016/s0749-0704(05)70148-2. PMID: 11219222

Recent systematic reviews

D'Souza AC, Wageh M, Williams JS, Colenso-Semple LM, McCarthy DG, McKay AKA, Elliott-Sale KJ, Burke LM, Parise G, MacDonald MJ, Tarnopolsky MA, Phillips SM
J Appl Physiol (1985) 2023 Dec 1;135(6):1284-1299. Epub 2023 Oct 12 doi: 10.1152/japplphysiol.00346.2023. PMID: 37823207Free PMC Article
Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, Park S, Hegyi P, Nyirády P, Ács N, Várbíró S, Horváth EM
Reprod Biol Endocrinol 2023 Jan 26;21(1):10. doi: 10.1186/s12958-023-01055-z. PMID: 36703143Free PMC Article
García-Hermoso A, Ramírez-Vélez R, Díez J, González A, Izquierdo M
J Sport Health Sci 2023 Mar;12(2):147-157. Epub 2022 Nov 6 doi: 10.1016/j.jshs.2022.11.003. PMID: 36351545Free PMC Article
Chaudhuri D, Sasaki K, Karkar A, Sharif S, Lewis K, Mammen MJ, Alexander P, Ye Z, Lozano LEC, Munch MW, Perner A, Du B, Mbuagbaw L, Alhazzani W, Pastores SM, Marshall J, Lamontagne F, Annane D, Meduri GU, Rochwerg B
Intensive Care Med 2021 May;47(5):521-537. Epub 2021 Apr 19 doi: 10.1007/s00134-021-06394-2. PMID: 33876268Free PMC Article
Nery C, Moraes SRA, Novaes KA, Bezerra MA, Silveira PVC, Lemos A
Braz J Phys Ther 2017 Nov-Dec;21(6):400-415. Epub 2017 Jul 5 doi: 10.1016/j.bjpt.2017.06.004. PMID: 28728958Free PMC Article

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