Primordial dwarfism

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Primordial dwarfism
SpecialtyMedical genetics

Primordial dwarfism (PD) is a form of dwarfism that results in a smaller body size in all stages of life beginning from before birth.[1] More specifically, primordial dwarfism is a diagnostic category including specific types of profoundly proportionate dwarfism, in which individuals are extremely small for their age, even as a fetus. Most individuals with primordial dwarfism are not diagnosed until they are about 3–5 years of age.

Medical professionals typically diagnose the fetus as being small for gestational age, or as showing intrauterine growth restriction when an ultrasound is conducted. Typically, people with primordial dwarfism are born with very low birth weights. After birth, growth continues at a much slower rate, leaving individuals with primordial dwarfism perpetually years behind their peers in stature and in weight.

Most cases of short stature are caused by skeletal or endocrine disorders. The five subtypes of primordial dwarfism are among the most severe forms of the 200 types of dwarfism.

There are as yet no effective treatments for primordial dwarfism. It is rare for individuals affected by primordial dwarfism to live past the age of 30.[2] In the case of microcephalic osteodysplastic primordial dwarfism type II (MOPDII), there can be increased risk of vascular problems, which may cause premature death.[3]


It is known that PD is caused by inheriting a mutant gene from each parent.[4] The lack of normal growth in the disorder is not due to a deficiency of growth hormone, as in hypopituitary dwarfism. Administering growth hormone, therefore, has little or no effect on the growth of the individual with primordial dwarfism, except in the case of Russell–Silver syndrome (RSS). Individuals with RSS respond favorably to growth hormone treatment. Children with RSS that are treated with growth hormone before puberty may achieve several inches of additional height. In January 2008, it was published that mutations in the pericentrin gene (PCNT) were found to cause primordial dwarfism.[5] Pericentrin has a role in cell division, proper chromosome segregation and cytokinesis.

Another gene that has been implicated in this condition is DNA2.[6] Mutations in this gene have been implicated in Seckel syndrome.


Since primordial dwarfism disorders are extremely rare, misdiagnosis is common. Because children with PD do not grow like other children, poor nutrition, a metabolic disorder, or a digestive disorder may be diagnosed initially. The correct diagnosis of PD may not be made until the child is 5 years old and it becomes apparent that the child has severe dwarfism.[citation needed]


Name OMIM Description
Seckel syndrome 210600 People with Seckel syndrome are noted to have microcephaly. Many also suffer from scoliosis, hip dislocation, delayed bone age, radial head dislocation, and seizures. Mutations in patients with Seckel syndrome have recently been identified in the gene encoding centrosomal protein CEP152 which is also mutated in some cases of primary isolated microcephaly.
Microcephalic osteodysplastic primordial dwarfism type I (MODPD1) (Taybi–Linder syndrome) 210710 This form of primordial dwarfism is often shortened to ODPDI. The corpus callosum of the brain is often undeveloped (called agenesis of the corpus callosum) and patients are known to have seizures and apnea. Hair thinness is also common, including scalp, hair, eyelashes and eyebrows. They suffer skeletally from short vertebrae, elongated clavicles, bent femora and hip displacement. Like those with Seckel syndrome, they also often have microcephaly. This syndrome is due to mutations in the RNU4ATAC gene. This gene, located on the long arm of chromosome 2 (2q14), encodes a small nuclear RNA component of the U12 dependent spliceosome.
Microcephalic osteodysplastic primordial dwarfism type II (MODPD2) 210720 Those who have ODPDII often have additional medical problems as compared with the other types, such as a squeaky voice, microdontia, widely spaced primary teeth, poor sleep patterns (in early years), delayed mental development, frequent sickness, breathing problems, eating problems, hyperactivity, farsightedness, and brain aneurysm. They do not respond to hormone therapy because primordial dwarfism is not caused by a lack of any growth hormone. After reviewing X-rays, it is also found that many have dislocated joints, scoliosis and delayed bone age as well as microcephaly. They will not reach the size of an average newborn until they are between the ages of 3 and 5. This condition is due to mutations in the PCNT gene located on the long arm of chromosome 21 (21q22). It encodes a protein known as pericentrin.
Silver–Russell dwarfism (Russell-Silver Syndrome) 180860 The final height of those with Russell–Silver syndrome often exceeds the height of others with primordial dwarfism, and they tend to have dysmorphic features. Some phenotypes (characteristics) of people who have Russell–Silver syndrome are inadequate catch-up growth in first 2 years, body asymmetry, lack of appetite, low-set posteriorly rotated ears, clinodactly (inward curving) of the 5th finger, webbed toes, non-descended testicles, weak muscle tone, delayed bone age, downturned corners of mouth and thin upper lip, hypospadias, high pitched voice, small chin, delayed closure of the fontanel, hypoglycemia, and a bossed forehead. Their heads may appear to be triangular shaped and large for their small body size.
Meier–Gorlin syndrome 224690 Individuals with Meier-Gorlin syndrome often have small ears and no kneecaps. They are also found to have curved clavicles, narrow ribs, and elbow dislocation. Like Russell–Silver syndrome, they usually exceed the height of those with Seckel syndrome and ODPDI and II. It is also known as "ear, patella, short stature syndrome" (EPS). Mutations in patients with Meier-Gorlin syndrome have recently been identified in a series of genes involved in chromosomal replication, specifically in the pre-replication complex. Specific genes include origin recognition complex genes ORC1, ORC4 and ORC6, as well as other replication genes CDT1 and CDC6.

Notable cases[edit]

See also[edit]


  1. ^ Fima Lifshitz (2007). Pediatric Endocrinology: Growth, adrenal, sexual, thyroid, calcium, and fluid balance disorders. CRC Press. pp. 15–. ISBN 978-1-4200-4270-2. Retrieved 7 January 2011.
  2. ^ The Smallest People in the World, TLC/Channel Four, 2006
  3. ^ "Primordial dwarfism" (PDF). American Journal of Medical Genetics. Archived from the original (PDF) on 9 December 2012.
  4. ^ National Geographic Channel Presents: Science of Dwarfism
  5. ^ Rauch, A.; Thiel, C.T.; Schindler, D.; Wick, U.; Crow, Y.J.; Ekici, A.B.; Van Essen, A.J.; Goecke, T.O.; Al-gazali, L.; Chrzanowska, K.H.; et al. (2008). "Mutations in the Pericentrin (PCNT) Gene Cause Primordial Dwarfism". Science. 319 (5864): 816–9. Bibcode:2008Sci...319..816R. doi:10.1126/science.1151174. PMID 18174396. S2CID 23055733.
  6. ^ Tarnauskaitė Ž, Bicknell LS, Marsh JA, Murray JE, Parry DA, Logan CV, Bober MB, de Silva DC, Duker AL, Sillence D, Wise C, Jackson AP, Murina O, Reijns MAM (2019) Biallelic variants in DNA2 cause microcephalic primordial dwarfism. Hum Mutat
  7. ^ "72-year-old Nepalese man from remote mountain village declared shortest human on record". The Washington Post. Retrieved 2012-02-28.[dead link]
  8. ^ "Smallest Siblings In the World Bridgette and Brad Jordan". Retrieved 10 February 2019.