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Severe postnatal growth retardation

MedGen UID:
347510
Concept ID:
C1857641
Finding
Synonyms: Marked growth retardation; Postnatal growth retardation, severe; Severe postnatal growth deficiency; Severe postnatal growth failure
 
HPO: HP:0008850

Definition

Severely slow or limited growth after birth, being four standard deviations or more below age- and sex-related norms. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Severe postnatal growth retardation

Conditions with this feature

Mietens syndrome
MedGen UID:
82695
Concept ID:
C0265249
Disease or Syndrome
Mietens syndrome is a very rare syndrome consisting of corneal opacity, nystagmus, strabismus, flexion contracture of the elbows with dislocation of the head of the radius and abnormally short ulnae and radii.
Isolated thyroid-stimulating hormone deficiency
MedGen UID:
78786
Concept ID:
C0271789
Disease or Syndrome
A type of central congenital hypothyroidism, a permanent thyroid deficiency that is present from birth, characterized by low levels of thyroid hormones due to a deficiency in TSH synthesis.
Cockayne syndrome type 1
MedGen UID:
155488
Concept ID:
C0751039
Disease or Syndrome
Cockayne syndrome (referred to as CS in this GeneReview) spans a continuous phenotypic spectrum that includes: CS type I, the "classic" or "moderate" form; CS type II, a more severe form with symptoms present at birth; this form overlaps with cerebrooculofacioskeletal (COFS) syndrome; CS type III, a milder and later-onset form; COFS syndrome, a fetal form of CS. CS type I is characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth percentile. Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability; death typically occurs in the first or second decade. CS type II is characterized by growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye may be present. Affected children have early postnatal contractures of the spine (kyphosis, scoliosis) and joints. Death usually occurs by age five years. CS type III is a phenotype in which major clinical features associated with CS only become apparent after age two years; growth and/or cognition exceeds the expectations for CS type I. COFS syndrome is characterized by very severe prenatal developmental anomalies (arthrogryposis and microphthalmia).
Alopecia - contractures - dwarfism - intellectual disability syndrome
MedGen UID:
167081
Concept ID:
C0795895
Disease or Syndrome
A form of ectodermal dysplasia syndrome characterized by a short stature of prenatal onset, alopecia, ichthyosis, photophobia, ectrodactyly, seizures, scoliosis, multiple contractures, fusions of various bones (particularly elbows, carpals, metacarpals, and spine), intellectual disability, and facial dysmorphism (microdolichocephaly, madarosis, large ears and long nose). ACD syndrome overlaps with ichthyosis follicularis-alopecia-photophobia syndrome.
Renal and mullerian duct hypoplasia
MedGen UID:
340326
Concept ID:
C1849439
Disease or Syndrome
Parana hard-skin syndrome
MedGen UID:
337964
Concept ID:
C1850079
Disease or Syndrome
A rare genetic skin disorder with characteristics of very early-onset of progressive skin thickening over the entire body (except for eyelids, neck and ears), progressively limited joint mobility with gradual freezing of joints and eventual severe chest and abdomen movement restriction, manifesting with restrictive pulmonary disease, which may lead to death. Additional features include severe growth restriction and osteoporosis. There have been no further descriptions in the literature since 1974.
Osteodysplastic primordial dwarfism, type 1
MedGen UID:
347149
Concept ID:
C1859452
Congenital Abnormality
Microcephalic osteodysplastic primordial dwarfism type I is a severe autosomal recessive skeletal dysplasia characterized by dwarfism, microcephaly, and neurologic abnormalities, including mental retardation, brain malformations, and ocular/auditory sensory deficits. Patients often die in early childhood (summary by Pierce and Morse, 2012).
4p partial monosomy syndrome
MedGen UID:
408255
Concept ID:
C1956097
Disease or Syndrome
Wolf-Hirschhorn syndrome is a congenital malformation syndrome characterized by pre- and postnatal growth deficiency, developmental disability of variable degree, characteristic craniofacial features ('Greek warrior helmet' appearance of the nose, high forehead, prominent glabella, hypertelorism, high-arched eyebrows, protruding eyes, epicanthal folds, short philtrum, distinct mouth with downturned corners, and micrognathia), and a seizure disorder (Battaglia et al., 2008).
Mucolipidosis type II
MedGen UID:
435914
Concept ID:
C2673377
Disease or Syndrome
GNPTAB-related disorders comprise the phenotypes mucolipidosis II (ML II) and mucolipidosis IIIa/ß (ML IIIa/ß), and phenotypes intermediate between ML II and ML IIIa/ß. ML II is evident at birth and slowly progressive; death most often occurs in early childhood. Orthopedic abnormalities present at birth may include thoracic deformity, kyphosis, clubfeet, deformed long bones, and/or dislocation of the hip(s). Growth often ceases in the second year of life; contractures develop in all large joints. The skin is thickened, facial features are coarse, and gingiva are hypertrophic. All children have cardiac involvement, most commonly thickening and insufficiency of the mitral valve and, less frequently, the aortic valve. Progressive mucosal thickening narrows the airways, and gradual stiffening of the thoracic cage contributes to respiratory insufficiency, the most common cause of death. ML IIIa/ß becomes evident at about age three years with slow growth rate and short stature; joint stiffness and pain initially in the shoulders, hips, and fingers; gradual mild coarsening of facial features; and normal to mildly impaired cognitive development. Pain from osteoporosis becomes more severe during adolescence. Cardiorespiratory complications (restrictive lung disease, thickening and insufficiency of the mitral and aortic valves, left and/or right ventricular hypertrophy) are common causes of death, typically in early to middle adulthood. Phenotypes intermediate between ML II and ML IIIa/ß are characterized by physical growth in infancy that resembles that of ML II and neuromotor and speech development that resemble that of ML IIIa/ß.
Short stature-pituitary and cerebellar defects-small sella turcica syndrome
MedGen UID:
394816
Concept ID:
C2678408
Disease or Syndrome
Short stature-pituitary and cerebellar defects-small sella turcica syndrome is characterised by short stature, anterior pituitary hormone deficiency, small sella turcica, and a hypoplastic anterior hypophysis associated with pointed cerebellar tonsils. It has been described in three generations of a large French kindred. Ectopia of the posterior hypophysis was observed in some patients. The syndrome is transmitted as a dominantly inherited trait and is caused by a germline mutation within the LIM-homeobox transcription factor <i>LHX4</i> gene (1q25).
Pituitary hormone deficiency, combined, 1
MedGen UID:
414421
Concept ID:
C2751608
Disease or Syndrome
Combined pituitary hormone deficiency (CPHD) in man denotes impaired production of growth hormone (GH; 139250) and one or more of the other 5 anterior pituitary hormones. Mutations of the POU1F1 gene in the human and Pit1 in the mouse are responsible for pleiotropic deficiencies of GH, prolactin (PRL; 176760), and thyroid-stimulating hormone (TSH; see 188540), while the production of adrenocorticotrophic hormone (ACTH; see 176830), luteinizing hormone (LH; 152780), and follicle-stimulating hormone (FSH; 136530) are preserved (Wu et al., 1998). Some patients exhibit only GH deficiency, although approximately 50% of isolated GH deficiency progresses to CPHD (Gergics et al., 2021). In infancy severe growth deficiency from birth as well as distinctive facial features with prominent forehead, marked midfacial hypoplasia with depressed nasal bridge, deep-set eyes, and a short nose with anteverted nostrils and hypoplastic pituitary gland by MRI examination can be seen (Aarskog et al., 1997). Some cases present with severe mental retardation along with short stature (Radovick et al., 1992). Reviews Voss and Rosenfeld (1992) reviewed the development and differentiation of the 5 pituitary cell types: galactotropes, gonadotropes, corticotropes, thyrotropes, and somatotropes. As indicated by the mutations in PIT1 described later, combined pituitary hormone deficiency can have either autosomal dominant or autosomal recessive inheritance, depending on the part of the PIT1 molecule affected by the mutation. Some mutations have a dominant-negative effect. Genetic Heterogeneity of Combined Pituitary Hormone Deficiency CPHD2 (262600), associated with hypogonadism, is caused by mutation in the PROP1 gene (601538). CPHD3 (221750), which is associated with rigid cervical spine and variable sensorineural deafness, is caused by mutation in the LHX3 gene (600577). CPHD4 (262700) is caused by mutation in the LHX4 gene (602146). CPHD5 (see septooptic dysplasia, 182230) is caused by mutation in the HESX1 gene (601802). CPHD6 (613986) is caused by mutation in the OTX2 gene (600037). CPHD7 (618160) is caused by mutation in the RNPC3 gene (618016).
Warburg micro syndrome 4
MedGen UID:
816595
Concept ID:
C3810265
Disease or Syndrome
RAB18 deficiency is the molecular deficit underlying both Warburg micro syndrome (characterized by eye, nervous system, and endocrine abnormalities) and Martsolf syndrome (characterized by similar – but milder – findings). To date Warburg micro syndrome comprises >96% of reported individuals with genetically defined RAB18 deficiency. The hallmark ophthalmologic findings are bilateral congenital cataracts, usually accompanied by microphthalmia, microcornea (diameter <10), and small atonic pupils. Poor vision despite early cataract surgery likely results from progressive optic atrophy and cortical visual impairment. Individuals with Warburg micro syndrome have severe to profound intellectual disability (ID); those with Martsolf syndrome have mild to moderate ID. Some individuals with RAB18 deficiency also have epilepsy. In Warburg micro syndrome, a progressive ascending spastic paraplegia typically begins with spastic diplegia and contractures during the first year, followed by upper-limb involvement leading to spastic quadriplegia after about age five years, often eventually causing breathing difficulties. In Martsolf syndrome infantile hypotonia is followed primarily by slowly progressive lower-limb spasticity. Hypogonadism – when present – manifests in both syndromes, in males as micropenis and/or cryptorchidism and in females as hypoplastic labia minora, clitoral hypoplasia, and small introitus.

Professional guidelines

PubMed

Marzano F, Chiara M, Consiglio A, D'Amato G, Gentile M, Mirabelli V, Piane M, Savio C, Fabiani M, D'Elia D, Sbisà E, Scarano G, Lonardo F, Tullo A, Pesole G, Faienza MF
Int J Mol Sci 2023 Jul 31;24(15) doi: 10.3390/ijms241512291. PMID: 37569667Free PMC Article

Recent clinical studies

Etiology

Blachowska E, Petriczko E, Horodnicka-Józwa A, Skórka A, Pelc M, Krajewska-Walasek M, Walczak M
Ital J Pediatr 2016 Jan 26;42:10. doi: 10.1186/s13052-015-0209-4. PMID: 26812928Free PMC Article
Nishimura G, Harigaya A, Kuwashima M, Kuwashima S
Am J Med Genet 1997 Jul 11;71(1):87-92. PMID: 9215775

Diagnosis

Verberne EA, Faries S, Mannens MMAM, Postma AV, van Haelst MM
Am J Med Genet A 2020 Aug;182(8):1952-1956. Epub 2020 May 28 doi: 10.1002/ajmg.a.61632. PMID: 32462814Free PMC Article
Lacassie Y, Johnson B, Lay-Son G, Quintana R, King A, Cortes F, Alvarez C, Gomez R, Vargas A, Chalew S, King A, Guardia S, Sorensen RU, Aradhya S
Am J Med Genet A 2020 Jul;182(7):1767-1775. Epub 2020 Apr 16 doi: 10.1002/ajmg.a.61597. PMID: 32297715
Blachowska E, Petriczko E, Horodnicka-Józwa A, Skórka A, Pelc M, Krajewska-Walasek M, Walczak M
Ital J Pediatr 2016 Jan 26;42:10. doi: 10.1186/s13052-015-0209-4. PMID: 26812928Free PMC Article
Feigerlova E, Hwa V, Derr MA, Rosenfeld RG
Endocr Dev 2013;24:118-27. Epub 2013 Feb 1 doi: 10.1159/000342586. PMID: 23392100
Ying YQ, Wei H, Cao LZ, Lu JJ, Luo XP
Zhongguo Dang Dai Er Ke Za Zhi 2007 Aug;9(4):335-8. PMID: 17706034

Therapy

Blachowska E, Petriczko E, Horodnicka-Józwa A, Skórka A, Pelc M, Krajewska-Walasek M, Walczak M
Ital J Pediatr 2016 Jan 26;42:10. doi: 10.1186/s13052-015-0209-4. PMID: 26812928Free PMC Article

Prognosis

Lessel D, Rading K, Campbell SE, Thiele H, Altmüller J, Gordon LB, Kubisch C
Am J Med Genet A 2022 Jan;188(1):216-223. Epub 2021 Oct 5 doi: 10.1002/ajmg.a.62525. PMID: 34611991

Clinical prediction guides

Stables J, Green EK, Sehgal A, Patkar OL, Keshvari S, Taylor I, Ashcroft ME, Grabert K, Wollscheid-Lengeling E, Szymkowiak S, McColl BW, Adamson A, Humphreys NE, Mueller W, Starobova H, Vetter I, Shabestari SK, Blurton-Jones MM, Summers KM, Irvine KM, Pridans C, Hume DA
Development 2022 Apr 15;149(8) Epub 2022 Mar 25 doi: 10.1242/dev.200237. PMID: 35333324Free PMC Article
Blachowska E, Petriczko E, Horodnicka-Józwa A, Skórka A, Pelc M, Krajewska-Walasek M, Walczak M
Ital J Pediatr 2016 Jan 26;42:10. doi: 10.1186/s13052-015-0209-4. PMID: 26812928Free PMC Article
Hammer E, Kutsche K, Haag F, Ullrich K, Sudbrak R, Willig RP, Braulke T, Kubler B
Eur J Endocrinol 2004 Oct;151(4):521-9. doi: 10.1530/eje.0.1510521. PMID: 15476454
Parks JS, Brown MR, Faase ME
J Pediatr 1997 Jul;131(1 Pt 2):S45-50. doi: 10.1016/s0022-3476(97)70011-8. PMID: 9255228

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