IllnessDwarfism, idiopathic; differential diagnosis

NGS +

[Sanger]

Human height is a polygenic trait with a heritability of about 80%. More than 700 common genetic variants explain 20% of the size variation in the normal population. Short stature is defined as height that is 2 standard deviations or more below the mean height for children of that sex and chronological age in a given population. This corresponds to a height that is below the 2.3 percentile. Two common causes of short stature are familial and constitutional delay in growth and puberty. Almost every serious systemic disease can lead to reduced growth as a secondary effect. Monogenic causes of dwarfism can follow all classical inheritance patterns. Furthermore, a large number of genetic syndromes and congenital malformations are associated with short stature, which can initially be excluded in part by means of chromosome analysis. Systematic phenotyping and extensive genetic tests make it possible to identify the underlying causes of short stature in over 30% of cases. But an inconspicuous genetic finding does not mean that genetic involvement can be excluded with certainty.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1215/

• Alias: Idiopathic short stature, ISS
• Allelic: ACTH-independent macronodular adrenal hyperplasia (GNAS)
• Allelic: Bladder cancer, somatic (FGFR3)
• Allelic: Brachydactyly, type A1 (IHH)
• Allelic: CATSHL syndrome (FGFR3)
• Allelic: Cervical cancer, somatic (FGFR3)
• Allelic: Colorectal cancer, somatic (FGFR3)
• Allelic: Crouzon syndrome with acanthosis nigricans (FGFR3)
• Allelic: Eiken syndrome (PTH1R)
• Allelic: Failure of tooth eruption, primary (PTH1R)
• Allelic: Hypercholesterolemia, familial, modifier of (GHR)
• Allelic: Increased responsiveness to growth hormone (GHR)
• Allelic: LADD syndrome (FGFR3)
• Allelic: Leri-Weill dyschondrosteosis (SHOX)
• Allelic: Leukemia, juvenile myelomonocytic, somatic (PTPN11)
• Allelic: Metachondromatosis (PTPN11)
• Allelic: Muenke syndrome (FGFR3)
• Allelic: Nevus, epidermal, somatic (FGFR3)
• Allelic: Osseous heteroplasia, progressive (GNAS)
• Allelic: SADDAN (FGFR3)
• Allelic: Spermatocytic seminoma, somatic (FGFR3)
• Allelic: Thanatophoric dysplasia, type I-II (FGFR3)
• Achondroplasia (FGFR3)
• Acid-labile subunit, deficiency of (IGFALS)
• Acrocapitofemoral dysplasia (IHH)
• Acromesomelic dysplasia 1, Maroteaux type (NPR2)
• Al-Gazali syndrome (B3GALT6)
• Chondrodysplasia, Blomstrand type (PTH1R)
• Ehlers-Danlos syndrome, spondylodysplastic type, 2 (B3GALT6)
• Epiphyseal chondrodysplasia, Miura type (NPR2)
• Growth hormone deficiency, isolated partial (GHSR)
• Growth hormone deficiency, isolated, type IA (GH1)
• Growth hormone deficiency, isolated, type IB (GH1)
• Growth hormone deficiency, isolated, type II (GH1)
• Growth hormone deficiency, isolated, type V (RNPC3)
• Growth hormone insensitivity with immune dysregulation 1, AR (STAT5B)
• Growth hormone insensitivity with immune dysregulation 2, AD (STAT5B)
• Growth hormone insensitivity, partial (GHR)
• Growth retardation with deafness and mental retardation due to IGF1 deficiency (IGF1)
• Hypochondroplasia (FGFR3)
• Insulin-like growth factor I, resistance to (IGF1R)
• Kowarski syndrome (GH1)
• LEOPARD syndrome 1 (PTPN11)
• Langer mesomelic dysplasia (SHOX)
• Laron dwarfism (GHR)
• Metaphyseal chondrodysplasia, Murk Jansen type (PTH1R)
• Metaphyseal chondrodysplasia, Schmid type (COL10A1)
• Noonan syndrome 1 (PTPN11)
• Pituitary hormone deficiency, combined or isolated, 7 (RNPC3)
• Pseudohypoparathyroidism Ia, Ib, Ic (GNAS)
• Pseudopseudohypoparathyroidism (GNAS)
• Short stature with nonspecific skeletal abnormalities (NPR2)
• Short stature, Dauber-Argente type (PAPPA2)
• Short stature, advanced bone age +/- early-onset osteoarthritis and/or osteochondritis disse. (ACAN)
• Short stature, idiopathic familial (SHOX)
• Silver-Russell syndrome 3 (IGF2)
• Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with/-out fractures (B3GALT6)
• Spondyloepimetaphyseal dysplasia, aggrecan type (ACAN)
• Spondyloepiphyseal dysplasia, Kimberley type (ACAN)