IllnessSmall stature, differential diagnosis

NGS +

[Sanger]

Short stature is defined as a height below the 3rd percentile, usually due to a reduced growth rate or a shortened growth period. Microsomia is particularly noticeable in infancy and during puberty, as this is when the growth spurts are normally greater. The spectrum of causes is extremely heterogeneous. Endogenous causes include genetic endocrine disorders, chromosomal anomalies, metabolic diseases and syndromal dwarfism.

Reference: https://pubmed.ncbi.nlm.nih.gov/28476223/

• Alias: Short stature
• Allelic: ACTH-independent macronodular adrenal hyperplasia (GNAS)
• Allelic: Agammaglobulinemia 7, AR (PIK3R1)
• Allelic: Agammaglobulinemia, XL 1 (BTK)
• Allelic: Anterior segment dysgenesis 4 (PITX2)
• Allelic: Aplastic anemia (NBN)
• Allelic: Beckwith-Wiedemann syndrome (CDKN1C)
• Allelic: Boucher-Neuhauser syndrome (PNPLA6)
• Allelic: Brachydactyly, type A2 (BMP2)
• Allelic: Brachydactyly, type B1 (ROR2)
• Allelic: Breast-ovarian cancer, familial, 2 (BRCA2)
• Allelic: CATSHL syndrome (FGFR3)
• Allelic: Cardiomyopathy, dilated, 1NN (RAf1)
• Allelic: Congenital myopathy with excess of muscle spindles (HRAS)
• Allelic: Cutaneous telangiectasia + cancer syndrome, familial (ATR)
• Allelic: Deafness, AD 20/26 (ACTG1)
• Allelic: Developmental + epileptic encephalopathy 85, with/-out midline brain defects (SMC1A)
• Allelic: Diabetes mellitus, insulin-resistant, with acanthosis nigricans (INSR)
• Allelic: Dystonia, juvenile-onset (ACTB)
• Allelic: Fibromatosis, gingival, 1 (SOS1)
• Allelic: Gigantism due to GHRF hypersecretion (GHRH)
• Allelic: Glomerulopathy with fibronectin deposits 2 (FN1)
• Allelic: Greig cephalopolysyndactyly syndrome (GLI3)
• Allelic: HFE hemochromatosis, modifier of (BMP2)
• Allelic: Hartsfield syndrome (FGFR1)
• Allelic: Hypercholesterolemia, familial, modifier of (GHR)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 5 (INSR)
• Allelic: Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Allelic: Immunodeficiency 36 (PIK3R1)
• Allelic: Increased responsiveness to growth hormone (GRH)
• Allelic: Jackson-Weiss syndrome (FGFR1)
• Allelic: Jawad syndrome (RBBP8) 3
• Allelic: Juvenile myelomonocytic leukemia (CBL)
• Allelic: LADD syndrome (FGFR3)
• Allelic: Leukemia, acute lymphoblastic (NBN)
• Allelic: McCune-Albright syndrome, somatic, mosaic (GNAS)
• Allelic: Meningioma, familial, susceptibility to (SMARCE1)
• Allelic: Microcephaly 6, primary, AR (CENPJ)
• Allelic: Microcephaly-micromelia syndrome (DONSON)
• Allelic: Microphthalmia, syndromic 5 (OTX2)
• Allelic: Monosomy 7 myelodysplasia and leukemia syndrome 2 (SAMD9)
• Allelic: Muenke syndrome (FGFR3)
• Allelic: Optic nerve hypoplasia + abnormalities of the central nervous system (SOX2)
• Allelic: Pfeiffer syndrome (FGFR1)
• Allelic: Polydactyly, postaxial, types A1 + B (GLI3)
• Allelic: Polydactyly, preaxial, type IV (GLI3)
• Allelic: Premature ovarian failure 11 (ERCC6)
• Allelic: RAS-associated autoimmune leukoproliferative disorder (KRAS)
• Allelic: Retinal dystrophy, early-onset, with/-out pituitary dysfunction (OTX2)
• Allelic: Ring dermoid of cornea (PITX2)
• Allelic: Septooptic dysplasia (HESX1)
• Allelic: Spastic paraplegia 39, AR (PNPLA6)
• Allelic: Trigonocephaly 1 (FGFR1)
• Allelic: Tumoral calcinosis, familial, normophosphatemic (SAMD9)
• Allelic: UV-sensitive syndrome 1 (ERCC6)
• Allelic: UV-sensitive syndrome 2 (ERCC8)
• Allelic: Wilms tumor (BRCA2)
• Allelic: Xeroderma pigmentosum, group F (ERCC4)
• Allelic: Xeroderma pigmentosum, type F
• 3-M syndrome 1 (CUL7)
• 3-M syndrome 2 (OBSL1)
• 3-M syndrome 3 (CCDC8)
• Aarskog-Scott syndrome (FGD1)
• Achondroplasia (FGFR3)
• Acid-labile subunit, deficiency of (IGFALS)
• Acromesomelic dysplasia, Maroteaux type (NPR2)
• Adrenocorticotropic hormone deficiency (TBX19)
• Alagille syndrome 2 (NOTCH2)
• Alazami syndrome (LARP7)
• Anauxetic dysplasia 2 (POP1)
• Arthrogryposis, cleft palate, craniosynostosis, impaired intellectual development (PPP3CA)
• Axenfeld-Rieger syndrome, type 1 (PITX2)
• Baraitser-Winter syndrome 1 (ACTB)
• Baraitser-Winter syndrome 2 (ACTG1)
• Bjornstad syndrome (BCS1L)
• Blepharophimosis-impaired intellectual development syndrome (SMARCA2)
• Bloom syndrome (BLM)
• Calvarial doughnut lesions with bone fragility +/- spondylometaphyseal dysplasia (SGMS2)
• Cardiofaciocutaneous syndrome (BRAF)
• Cardiofaciocutaneous syndrome 2 (KRAS)
• Cardiofaciocutaneous syndrome 3 (MAP3K1)
• Cardiofaciocutaneous syndrome 4 (MAP2K2)
• Cerebrooculofacioskeletal syndrome 1 (ERCC6)
• Cockayne syndrome (ERCC4)
• Cockayne syndrome, type A (ERCC8)
• Cockayne syndrome, type B (ERCC6)
• Coffin-Lowry syndrome (RPS6KA3)
• Coffin-Siris syndrome 5 (SMARCE1)
• Cornelia de Lange syndrome 1 (NIPBL)
• Cornelia de Lange syndrome 2 (SMC1A)
• Cornelia de Lange syndrome 3 (SMC3)
• Cornelia de Lange syndrome 4 (RAD21)
• Cornelia de Lange syndrome 5 (HDAC8)
• Costello syndrome (HRAS)
• Crouzon syndrome with acanthosis nigricans (FGFR3)
• Culler-Jones syndrome (GLI2)
• De Sanctis-Cacchione syndrome (ERCC6)
• Developmental and epileptic encephalopathy 91 (PPP3CA)
• Encephalopathy, progressive, with amyotrophy + optic atrophy (TBCE)
• Epiphyseal chondrodysplasia, Miura type (NPR2)
• Fanconi anemia, complementation group A-L (FANCA-L)
• Fanconi anemia, complementation group D1 (BRCA2)
• Fanconi anemia, complementation group D2 (FANCD2)
• Fanconi anemia, complementation group J (BRIP1)
• Fanconi anemia, complementation group N (PALB2)
• Fanconi anemia, complementation group P (SLX4)
• Fanconi anemia, complementation group Q (ERCC4)
• Fanconi anemia, complementation group T (UBE2T)
• Floating-Harbor syndrome (SRCAP)
• GRACILE syndrome (BCS1L)
• Galloway-Mowat syndrome 3 (OSGEP)
• Growth hormone deficiency with pituitary anomalies (HESX1)
• Growth hormone deficiency, isolated partial (GHSR)
• Growth hormone deficiency, isolated, type IA, IB, II (GH1)
• Growth hormone deficiency, isolated, type IV (GHRHR)
• Growth hormone insensitivity with immunodeficiency (STAT5B)
• Growth hormone insensitivity, partial (GHR)
• Growth retardation with deafness + mental retardation due to IGF1 deficiency (IGF1)
• Hajdu-Cheney syndrome (NOTCH2)
• Hiatt-Neu-Cooper neurodevelopmental syndrome (RALA)
• Holoprosencephaly 9 (GLI2)
• Hypochondroplasia (FGFR3)
• Hypoparathyroidism-retardation-dysmorphism syndrome (TBCE)
• IMAGE syndrome (CDKN1C)
• Insulin-like growth factor I, resistance to (IGF1R)
• Intellectual dev. disorder, microcephaly +/- ocular malformations/hypogonad. hypogonadism (SOX11)
• Intellectual developmental disorder, XL 19 (RPS6KA3)
• Intellectual developmental disorder, XL, syndromic, 35 (RPL10)
• Intellectual developmental disorder, XL, with isolated growth hormone deficiency (SOX3)
• Isolated growth hormone deficiency due to defect in GHRF (GHRH) 1
• Isolated growth hormone deficiency, type III, with agammaglobulinemia (BTK)
• KBG syndrome (ANKRD11)
• Kabuki syndrome 1 (KMT2D)
• Kabuki syndrome 2 (KDM6A)
• Kenny-Caffey syndrome, type (TBCE)
• Kowarski syndrome (GH1)
• LEOPARD syndrome 1 (PTPN11)
• LEOPARD syndrome 2 (RAF1)
• LEOPARD syndrome 3 (BRAF)
• LIG4 syndrome (LIG4)
• Langer mesomelic dysplasia (SHOX)
• Laron dwarfism (GHR)
• Laurence-Moon syndrome (PNPLA6)
• Leprechaunism (INSR)
• Leri-Weill dyschondrosteosis (SHOX)
• Liberfarb syndrome (PISD)
• Lowry-Wood syndrome (RNU4ATAC)
• MIRAGE syndrome (SAMD9)
• Meier-Gorlin syndrome 1 (ORC1)
• Meier-Gorlin syndrome 2 (ORC4)
• Meier-Gorlin syndrome 3 (ORC6)
• Meier-Gorlin syndrome 4 (CDT1)
• Meier-Gorlin syndrome 5 (CDC6)
• Meier-Gorlin syndrome 7 (CDC45)
• Menke-Hennekam syndrome 1 (CREBBP)
• Menke-Hennekam syndrome 2 (EP300)
• Mental retardation, XL syndromic 16 (FGD1)
• Metachondromatosis (PTPN11)
• Microcephalic osteodysplastic primordial dwarfism, type I (RNU4ATAC)
• Microcephalic osteodysplastic primordial dwarfism, type II (PCNT)
• Microcephaly 9, primary, AR (CEP152)
• Microcephaly, growth restriction + increased sister chromatid exchange 2 (TOP3A)
• Microcephaly, short stature + impaired glucose metabolism 1 (TRMT10A)
• Microcephaly, short stature + limb abnormalities (DONSON)
• Microcephaly, short stature + polymicrogyria with seizures (RTTN)
• Microphthalmia, syndromic 3 (SOX2)
• Midface hypoplasia, hearing impairment, elliptocytosis, nephrocalcinosis (AMMECR1)
• Mitochondrial complex III deficiency, nuclear type 1 (BCS1L)
• Mucopolysaccharidosis Ih, Ih/s, Is (IDUA)
• Mulibrey nanism (TRIM37)
• Multiple joint dislocations, short, craniofacial dysmorphism +/- cong. heart defects (B3GAT3)
• Mungan syndrome (RAD21)
• Nicolaides-Baraitser syndrome (SMARCA2)
• Nijmegen breakage syndrome (NBN)
• Noonan syndrome 1 (PTPN11)
• Noonan syndrome 10 (LZTR1)
• Noonan syndrome 2 (LZTR1)
• Noonan syndrome 3 (KRAS)
• Noonan syndrome 4 (SOS1)
• Noonan syndrome 5 (RAF1)
• Noonan syndrome 6 (NRAS)
• Noonan syndrome 7 (BRAF)
• Noonan syndrome 8 (RIT1)
• Noonan syndrome 9 (SOS2)
• Noonan syndrome [panelapp] (RASA2)
• Noonan syndrome, atypical [panelapp] (RRAS)
• Noonan syndrome-like disorder with loose anagen hair 2 (PPP1CB)
• Noonan syndrome-like disorder with/-out juvenile myelomonocytic leukemia (CBL)
• Noonan syndrome-like with loose anagen hair 1 (SHOC2)
• Oliver-McFarlane syndrome (PNPLA6)
• Osseous heteroplasia, progressive (GNAS)
• Osteoglophonic dysplasia (FGFR1)
• Pallister-Hall syndrome (GLI3)
• Panhypopituitarism, XL (SOX3)
• Pituitary hormone deficiency, combined or isolated, 7 (RNPC3)
• Pituitary hormone deficiency, combined, 1 (POUF1)
• Pituitary hormone deficiency, combined, 2 (PROP1)
• Pituitary hormone deficiency, combined, 3 (LHX3)
• Pituitary hormone deficiency, combined, 4 (LHX4)
• Pituitary hormone deficiency, combined, 5 (HESX1)
• Pituitary hormone deficiency, combined, 6 (OTX2)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 5 (TOP3A)
• Pseudohypoparathyroidism Ia, Ib, Ic (GNAS)
• Pseudopseudohypoparathyroidism (GNAS)
• Rabson-Mendenhall syndrome (INSR)
• Robinow syndrome, AD 1 (WNT5A)
• Robinow syndrome, AD 2 (DVL1)
• Robinow syndrome, AD 3 (DVL3)
• Robinow syndrome, AR (ROR2)
• Roifman syndrome (RNU4ATAC)
• Rubinstein-Taybi syndrome 1 (CREBBP)
• Rubinstein-Taybi syndrome 2 (EP300)
• SADDAN (FGFR3)
• SHORT syndrome (PIK3R1)
• Seckel syndrome 1 (ATR)
• Seckel syndrome 2 (RBBP8)
• Seckel syndrome 4 (CENPJ)
• Seckel syndrome 5 (CEP152)
• Seckel syndrome 6 (CEP63)
• Short stature with microcephaly and distinctive facies (CRIPT)
• Short stature with nonspecific skeletal abnormalities (NPR2)
• Short stature, Dauber-Argente type (PAPPA2)
• Short stature, advanced bone age +/- early-onset osteoarthritis +/- osteochondritis dissecans (ACAN)
• Short stature, brachydactyly, intellectual developmental disability + seizures (PRMT7)
• Short stature, facial dysmorphism, skeletal anomalies +/- cardiac anomalies 1 (BMP2)
• Short stature, idiopathic familial (SHOX)
• Short stature, microcephaly + endocrine dysfunction (XRCC4)
• Short stature, onychodysplasia, facial dysmorphism + hypotrichosis (POC1A)
• Short stature, rhizomelic with microcephaly, micrognathia, developmental delay (ARCN1)
• Short stature-micrognathia syndrome (ARCN1)
• Silver-Russell syndrome 3 (IGF2)
• Silver-Russell syndrome 4 (PLAG1)
• Silver-Russell syndrome 5 (HMGA2)
• Smith-Lemli-Opitz syndrome (DHCR7)
• Spondylocostal dysostosis 3, AR (LFNG)
• Spondyloepimetaphyseal dysplasia, aggrecan type (ACAN)
• Spondyloepiphyseal dysplasia, Kimberley type (ACAN)
• Spondylometaphyseal dysplasia, corner fracture type (FN1)
• Steel syndrome (COL27A1)
• Thanatophoric dysplasia, type I + II (FGFR3)
• Transaldolase deficiency (TALDO1)
• Ulnar-mammary syndrome (TBX3)
• Verheij syndrome (PUF60)
• Vertebral anomalies + variable endocrine and T-cell dysfunction (TBX2)
• Werner syndrome (WRN)
• XFE progeroid syndrome (ERCC4)