Genitopatellar syndrome

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Genitopatellar syndrome
Other namesAbsent patellae-scrotal hypoplasia-renal anomalies-facial dysmorphism-intellectual disability syndrome [1]

Genitopatellar syndrome is a rare disorder consisting of congenital flexion contractures of the lower extremities, abnormal or missing patellae, and urogenital anomalies. Additional symptoms include microcephaly, severe psychomotor disability. [2] In 2012, it was shown that mutations in the gene KAT6B cause the syndrome. [3] Genitopatellar syndrome (GTPTS) can be caused by heterozygous mutation in the KAT6B gene on chromosome 10q22. The Say-Barber-Biesecker variant of Ohdo syndrome, which has many overlapping features with GTPTS, can also be caused by heterozygous mutation in the KAT6B gene. [2]

Contents

Signs and symptoms

Genitopatellar syndrome is characterized by genital abnormalities, missing or underdeveloped kneecaps (patellae), intellectual disability and abnormalities affecting other parts of the body. It is also associated with delayed development and intellectual disability, which are often severe. Affected individuals may have an unusually small head (microcephaly) and structural brain abnormalities, including agenesis of the corpus callosum. [4]

Major features include: [4] [5] [6]

Other features may include: [4]

Cause

Genitopatellar syndrome is inherited in an autosomal dominant fashion. The mutation responsible for the syndrome occurs in the KAT6B gene. This gene is located on the long arm of chromosome 10 (10q22.2). [7]

The KAT6B gene gene product is an enzyme called histone acetyltransferase which functions in regulating and making of histone which are proteins that attach to DNA and give the chromosomes their shape. The function of histone acetyltransferase produced from KAT6B is unknown but it is considered as a regulator of early development. There is little known about how the mutation in the KAT6B causes the syndrome but researchers suspects that the mutations occur near the end of the KAT6B gene and causes it to produce shortened acetyltransferase enzyme. The shortened enzyme alters the regulation of other genes. On the other hand, the mutation of KAT6B leading to the specific features of genitopatellar syndrome is still not surely proven. [8]

Diagnosis

Even though clinical diagnostic criteria have not been 100 percent defined for genitopatellar syndrome, the researchers stated that the certain physical features could relate to KAT6B mutation and result in the molecular genetic testing. The researchers stated that the Individuals with two major features or one major feature and two minor features are likely to have a KAT6B mutation. To diagnose the Genitopatellar Syndrome, there are multiple ways to evaluate. The primary method of diagnosing Genitopatellar Syndrome is through molecular genetic testing. [9] [10] [11]

[12]

Treatment

There is no cure for genitopatellar syndrome. However, there are treatments for the different symptoms. For the developmental symptoms, Educational intervention and speech therapy beginning in infancy could help to reduce the high risk for motor, cognitive, speech, and language delay. For the skeletal features, referral to an orthopedist for consideration of surgical release of contractures. In addition, early referral to physical therapy could help increase joint mobility. Lastly, thyroid hormone replacement could help out the thyroid dysfunction. [4]

History

In 1988, Goldblatt et al. first reported a 4-year-old boy with hypoplastic patellae, mental retardation, scrotal hypoplasia, skeletal deformities, kidney anomalies, flattened nasal bridge, and short stature. Later in 2000, Cormier-Daire et al. reported seven patients with genital anomalies (scrotal hypoplasia and cryptorchidism in the boys and clitoral hypertrophy in the girls), facial dysmorphism, kidney anomalies, absent patellae, and severe mental retardation in the two survivors. The condition is now known as genitopatellar syndrome. [13]

See also

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References

  1. ↑ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Genitopatellar syndrome". www.orpha.net. Retrieved 15 March 2019.
  2. 1 2 Penttinen, M; Koillinen, H; Niinikoski, H; Mäkitie, O; Hietala, M (March 2009). "Genitopatellar syndrome in an adolescent female with severe osteoporosis and endocrine abnormalities". American Journal of Medical Genetics. Part A. 149A (3): 451–5. doi:10.1002/ajmg.a.32644. PMID   19208376. S2CID   13523168.
  3. ↑ Campeau PM, Kim JC, Lu JT, Schwartzentruber JA, Abdul-Rahman OA, Schlaubitz S, Murdock DM, Jiang MM, Lammer EJ, Enns GM, Rhead WJ, Rowland J, Robertson SP, Cormier-Daire V, Bainbridge MN, Yang XJ, Gingras MC, Gibbs RA, Rosenblatt DS, Majewski J, Lee BH (Jan 2012). "Mutations in KAT6B, Encoding a Histone Acetyltransferase, Cause Genitopatellar Syndrome". American Journal of Human Genetics . 90 (2): 282–9. doi:10.1016/j.ajhg.2011.11.023. PMC   3276659 . PMID   22265014.
  4. 1 2 3 4 Adam, M. P.; Mirzaa, G. M.; Pagon, R. A.; Wallace, S. E.; Bean LJH; Gripp, K. W.; Amemiya, A.; Lemire, G.; Campeau, P. M.; Lee, B. H. (1993). "KAT6B-Related Disorders". GeneReviews®. University of Washington, Seattle. PMID   23236640.
  5. ↑ "Clinical Signs and Symptoms Orphanet ORPHA:85201".
  6. ↑ Zhang, LX; Lemire, G; Gonzaga-Jauregui, C; Molidperee, S; Galaz-Montoya, C; Liu, DS; Verloes, A; Shillington, AG; Izumi, K; Ritter, AL; Keena, B; Zackai, E; Li, D; Bhoj, E; Tarpinian, JM; Bedoukian, E; Kukolich, MK; Innes, AM; Ediae, GU; Sawyer, SL; Nair, KM; Soumya, PC; Subbaraman, KR; Probst, FJ; Bassetti, JA; Sutton, RV; Gibbs, RA; Brown, C; Boone, PM; Holm, IA; Tartaglia, M; Ferrero, GB; Niceta, M; Dentici, ML; Radio, FC; Keren, B; Wells, CF; Coubes, C; Laquerrière, A; Aziza, J; Dubucs, C; Nampoothiri, S; Mowat, D; Patel, MS; Bracho, A; Cammarata-Scalisi, F; Gezdirici, A; Fernandez-Jaen, A; Hauser, N; Zarate, YA; Bosanko, KA; Dieterich, K; Carey, JC; Chong, JX; Nickerson, DA; Bamshad, MJ; Lee, BH; Yang, XJ; Lupski, JR; Campeau, PM (August 2020). "Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants". Genetics in Medicine. 22 (8): 1338–1347. doi:10.1038/s41436-020-0811-8. PMC   7737399 . PMID   32424177.
  7. ↑ Kim, YR; Park, JB; Lee, YJ; Hong, MJ; Kim, HT; Kim, HJ (June 2017). "Identifying the KAT6B Mutation via Diagnostic Exome Sequencing to Diagnose Say-Barber-Biesecker-Young-Simpson Syndrome in Three Generations of a Family". Annals of Rehabilitation Medicine. 41 (3): 505–510. doi:10.5535/arm.2017.41.3.505. PMC   5532359 . PMID   28758091.
  8. ↑ "Genitopatellar syndrome".
  9. ↑ Campeau, PM; Kim, JC; Lu, JT; Schwartzentruber, JA; Abdul-Rahman, OA; Schlaubitz, S; Murdock, DM; Jiang, MM; Lammer, EJ; Enns, GM; Rhead, WJ; Rowland, J; Robertson, SP; Cormier-Daire, V; Bainbridge, MN; Yang, XJ; Gingras, MC; Gibbs, RA; Rosenblatt, DS; Majewski, J; Lee, BH (10 February 2012). "Mutations in KAT6B, encoding a histone acetyltransferase, cause Genitopatellar syndrome". American Journal of Human Genetics. 90 (2): 282–9. doi:10.1016/j.ajhg.2011.11.023. PMC   3276659 . PMID   22265014.
  10. ↑ Lonardo, F; Lonardo, MS; Acquaviva, F; Della Monica, M; Scarano, F; Scarano, G (February 2019). "Say-Barber-Biesecker-Young-Simpson syndrome and Genitopatellar syndrome: Lumping or splitting?". Clinical Genetics. 95 (2): 253–261. doi:10.1111/cge.13127. PMID   28857140. S2CID   23422319.
  11. ↑ Simpson, MA; Deshpande, C; Dafou, D; Vissers, LE; Woollard, WJ; Holder, SE; Gillessen-Kaesbach, G; Derks, R; White, SM; Cohen-Snuijf, R; Kant, SG; Hoefsloot, LH; Reardon, W; Brunner, HG; Bongers, EM; Trembath, RC (10 February 2012). "De novo mutations of the gene encoding the histone acetyltransferase KAT6B cause Genitopatellar syndrome". American Journal of Human Genetics. 90 (2): 290–4. doi:10.1016/j.ajhg.2011.11.024. PMC   3276665 . PMID   22265017.
  12. ↑ Lemire, Gabrielle; Campeau, Philippe M.; Lee, Brendan H. (1993). "KAT6B Disorders". GeneReviews®. University of Washington, Seattle. PMID   23236640.
  13. ↑ Chen, Harold (2017). "Genitopatellar Syndrome". Atlas of Genetic Diagnosis and Counseling. pp. 1221–1226. doi:10.1007/978-1-4939-2401-1_105. ISBN   978-1-4939-2400-4.
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