OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (CUL7). Hypogonadism and hypospadias have been described in only a few males. We report a patient with CUL7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome.

Department of Children and Adolescents Faculty Hospital Kralovske Vinohrady 3rd Faculty of Medicine Charles University 100 34 Prague 10 Czech Republic

Department of Clinical Genetics Birmingham Women´s and Children´s Hospital B15 2TG Birmingham UK

Department of Paediatric Endocrinology and Diabetes Birmingham Women´s and Children´s Hospital B4 6NH Birmingham UK

Institute of Metabolism and Systems Research University of Birmingham B15 2TT Birmingham UK

Zobrazit více v PubMed

Hanson  D, Murray  PG, Coulson  T, et al.  Mutations in CUL7, OBSL1, and CCDC8 in 3-M syndrome lead to disordered growth factor signaling. J Mol Endocrinol. 2012;49(3):261‐275. PubMed

Irving  M, Holder-Espinasse  M. Three M Syndrome. 2002 Mar 25 [Updated 2019 Feb 7]. In: Adam MP, Feldman J, Mirzaa GM, et al., eds.  GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Bookshelf. https://www.ncbi.nlm.nih.gov/books/

Simsek-Kiper  PO, Taskiran  E, Kosukcu  C, et al.  Further expanding the mutational spectrum and investigation of genotype-phenotype correlation in 3 M syndrome. Am J Med Genet A. 2019;179(7):1157‐1172. PubMed

Meazza  C, Lausch  E, Pagani  S, et al.  3-M syndrome associated with growth hormone deficiency: 18-year follow-up of a patient. Ital J Pediatr. 2013;39(1):21. PubMed PMC

Murray  PG, Hanson  D, Coulson  T, et al.  3-M syndrome: a growth disorder associated with IGF2 silencing. Endocr Connect. 2013;2(4):225‐235. PubMed PMC

Clayton  PE, Hanson  D, Magee  L, et al.  Exploring the spectrum of 3-M syndrome, a primordial short stature disorder of disrupted ubiquitination. Clin Endocrinol (Oxford). 2012;77(3):335‐342. PubMed

Maksimova  N, Hara  K, Miyashia  A, et al.  Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia. J Med Genet. 2007;44(12):772‐778. PubMed PMC

Kelsey  TW, Miles  A, Mitchell  RT, et al.  A normative model of serum inhibin B in young males. PLoS One. 2016;11(4):e0153843. PubMed PMC

Deeb  A, Afandi  O, Attia  S, El Fatih  A. 3-M syndrome: a novel CUL7 mutation associated with respiratory distress and a good response to GH therapy. Endocrinol Diabetes Metab Case Rep. 2015;2015:150012. PubMed PMC

Jensen  TK, Andersson  AM, Hjollund  NH, et al.  Inhibin B as a serum marker of spermatogenesis: correlation to differences in sperm concentration and follicle-stimulating hormone levels. A study of 349 Danish men. J Clin Endocrinol Metab. 1997;82(12):4059‐4063. PubMed

Dauber  A, Stoler  J, Hechter  E, Safer  J, Hirschhorn  JN. Whole exome sequencing reveals a novel mutation in CUL7 in a patient with an undiagnosed growth disorder. J Pediatr. 2013;162(1):202‐204. PubMed PMC