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 Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 35  |  Issue : 2  |  Page : 82-84

Phocomelia: case report of a rare congenital disorder


Department of Medicine, Government Medical College Srinagar, Srinagar, Jammu and Kashmir, India

Date of Submission11-Apr-2015
Date of Acceptance01-Jun-2015
Date of Web Publication10-Mar-2016

Correspondence Address:
Ishrat H Dar
MD, Assistant Professor, Department of Medicine, Government Medical College Srinagar, Srinagar - 190 010, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-6530.162227

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  Abstract 

Phocomelia is an extremely rare malformation in which babies are born with limbs that appear similar to the flippers of a seal. Although various factors can cause phocomelia, the prominent roots came from the use of thalidomide and from genetic inheritance. Phocomelia is transmitted as an autosomal recessive trait with variable expressivity, and malformation is linked to chromosome 8. Presented here is the incidental detection of phocomelia in a young man with no history of thalidomide intake and for whom evaluation of other family members/siblings failed to reveal any substantial abnormality, making it a probable case of sporadic mutation-induced phocomelia.

Keywords: autosomal recessive, chromosome 8, phocomelia, sporadic, thalidomide


How to cite this article:
Dar IH, Dar MI, Farooq O, Mir SR. Phocomelia: case report of a rare congenital disorder . Egypt J Dermatol Venerol 2015;35:82-4

How to cite this URL:
Dar IH, Dar MI, Farooq O, Mir SR. Phocomelia: case report of a rare congenital disorder . Egypt J Dermatol Venerol [serial online] 2015 [cited 2019 Sep 23];35:82-4. Available from: http://www.ejdv.eg.net/text.asp?2015/35/2/82/162227


  Introduction Top


Phocomelia is a rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being more severely affected. Extreme cases show absence of the most proximal elements to the shoulder, or attachment of the hands or fingers directly to the shoulder. The typical picture includes defects of the arms (amelia, atypical phocomelia with absence of the hands or fingers, and aplasia of the radius), defects of the long bones of the legs, especially the femora and tibiae. The disorder previously known in both autosomal recessive and sporadic forms increased in incidence in the 1960s in the West due to the widespread use of the teratogenic drug thalidomide prescribed to pregnant women [1]. The word phocomelia combines 'phoco' denoting seal and 'melia' denoting limb to signify a limb similar to a seal's flipper. Although a number of factors can cause phocomelia, the most common has been due to thalidomide intake and from genetic inheritance [2],[3].


  Case report Top


A 29-year-old unmarried young man born of a nonconsanguineous marriage presented to the medical emergency of our hospital as a case of rodenticide poisoning due to prolonged depressive state. Examination revealed a conscious and cooperative moderately built young man of normal intelligence without any overt features of poisoning. General physical examination of the patient was remarkable in the sense that the upper limb showed partial absence of phalanges in both hands, flexion contractures in both thumb bones, and a rudimentary terminal phalange and nail in the right middle finger. Examination of both feet revealed a bilateral club foot, shortening of both feet, an everted big toe with absence of the second and third toes and rudimentary fourth and fifth toes on the right side, and all but small poorly formed toes on the left side [Figure 1],[Figure 2] and [Figure 3]. A detailed search for other bony anomalies failed to reveal any abnormality elsewhere. Examination of the chest, abdomen, and the cardiovascular and the central nervous system was normal. Detailed family history including congenital anomalies, drug intake by the mother during pregnancy, or exposure neither to X-ray irradiation nor to pesticides was evident. Routine investigations including complete blood count, urine examination, blood sugar, kidney and liver function tests, prothrombin time, electrolytes, ECG, radiography of the chest in posteroanterior view, and ultrasonography of the abdomen were normal. The patient refused consent for further evaluation, including radiography of the hands/feet and genetic testing. Examination of two other siblings was unremarkable and it was presumed that the deformity in the patient was probably of sporadic nature. The patient was managed symptomatically and discharged in a satisfactory condition after 2 days of hospitalization.
Figure 1: Features of phocomelia with partial absence of structures in both hands and feet.

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Figure 2: Partial absence of phalanges in both hands, flexion contractures in both the thumb bones, and a rudimentary terminal phalange and nail in the right middle finger.

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Figure 3: Examination of both feet revealed a bilateral club foot, shortening of both feet, an everted big toe, with absence of the second and third toes and rudimentary fourth and fi fth toes on the right side, and all but small poorly formed toes on the left side.

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  Discussion Top


The first case of phocomelia was described in Germany in 1956 in a baby whose mother had received thalidomide during pregnancy, in which the baby was born with only vestigial flipper-like hands without arms. Thalidomide was used as a sedative or hypnotic and was claimed to cure anxiety, depression, gastritis, and insomnia. It was used to combat nausea and alleviate early morning sickness in pregnant women. Between 5000 and 7000 babies were born with phocomelia, of whom only 40% of babies whose mothers had taken thalidomide during the first trimester of pregnancy survived in Germany [4]. From Germany, Lenz reported having seen 52 malformed infants whose mothers had received thalidomide during early pregnancy. There were 115 additional cases in which the drug was thought to be implicated. The typical picture included defects of the arms (amelia, atypical phocomelia with absence of the hands or fingers, and aplasia of the radius), defects of the long bones of the legs, especially the femora and tibiae, absence of the auricles, hemangiomata of the nose and upper lip (port-wine stain), atresia of the esophagus, duodena, or anus, cardiac anomalies, and aplasia of the gall bladder and appendix. Lenz estimated that at least 2000, and possibly more than 3000, 'thalidomide babies' had been born in West Germany since 1959. Tetra phocomelia is a severe combination of limb defects in which total or partial agenesis of the upper and lower limbs is seen, leading to the proximity of limbs to the trunk of the fetus, resembling the flippers of a seal (an aquatic animal). Such babies are termed as thalidomide babies a consequence of dysmorphogenesis of limb buds due to the use of this drug during 1960s. In fact, such defects were reported even centuries earlier attributing X-ray irradiation and genetic (autosomal recessive) and sporadic anomalies as causes. The drug was withdrawn from the German market on 27 November 1961. The symptoms of the phocomelia syndrome are underdeveloped limbs and absent pelvic bones. Usually, the upper limbs are not fully formed and sections of the hands and arms may be missing. Short arm bones, fused fingers, and missing thumbs often occur. Legs and feet are also affected similar to that of the arms and the hands, as was evident in our case, although there was no history of thalidomide exposure in our case [4],[5] (en.wikipedia.org/wiki/Phocomelia). Thalidomide has been effectively linked to widespread severe disabilities or death among babies from Europe and Australia with in-utero deformities ranging from limb defects, deformed eyes, hearts, alimentary and urinary tract anomalies, blindness, and deafness [6],[7].

According to the National Organization for Rare Disorders (NORD), when phocomelia is transmitted in its familial genetic form it is seen as an autosomal recessive trait and the mutation is linked to chromosome 8. There are several attachment points in a chromosome, and the centromere is the major connection point where the immensity of the work generates. Embryological basis of malformation of limbs shows that an individual will have chromosome copies that do not connect at centromeres, making them unable to move to the equatorial plane of spindle during metaphase of cell division. As a result, the cell becomes incapable of division or slow in process, because of this the newly made cells contain an excessive or reduced amount of chromatin. In phocomelia, the cells cease to develop or die, preventing proper development of limbs, eyes, palate, brain, or other structures [2],[3],[8]. Limb defects are caused by genetic factors such as chromosomal abnormalities associated with trisomy 18, mutant genes, environmental factors such as teratogens, a combination of genetic and environmental factors (multifactorial inheritance), vascular disruption, and ischemia, as in limb reduction defects [9].

The differential diagnosis includes sporadic phocomelia, Holt-Oram syndrome, thrombocytopenia-absent radius syndrome, Roberts syndrome, and thalidomide-induced phocomelia. Sporadic phocomelia is a very rare genetic disorder inherited as an autosomal recessive trait, or as the result of spontaneous mutations [10]. In such cases, there is 25% chance for a child to be affected, provided both parents are carriers. Thus, there is significantly increased risk for phocomelia when parents have consanguinity. However, without the ability to obtain a reliable family history, the presence of hereditary phocomelia cannot be determined. Thrombocytopenia-absent radius syndrome is characterized by a low platelet count, an absent radius, a hypoplastic thumb, and cardiac abnormalities [11]. Roberts syndrome is an extremely rare disorder that has been described in only 150 individuals around the world; it is characterized by malformation of the bones in the face, skull, arms, and legs [12]. Holt-Oram syndrome may be seen both as an autosomal dominant disorder and as the result of spontaneous genetic mutations. This syndrome is characterized by an abnormal limb development that affects mostly the forearm and the carpal bones of the wrists. Characteristic features include a hypoplastic thumb or a thumb that appears similar to a finger. Frequently, the radius is missing and the humerus is underdeveloped. The clavicle and scapula may be affected. Three-quarters of the patients with Holt-Oram syndrome have cardiac problems that may include atrial septal defects or ventricular septal defects [13].

Most of the anomalies can be diagnosed antenatally if an anomaly scan is performed at around 18-20 weeks of gestation, and all pregnant women should be advised to undergo ultrasonography to rule out anomalies in the baby.


  Acknowledgements Top


Author contributions: I.H.D. and M.I.D.: examined and admitted the patient and made the diagnosis; I.H.D.: wrote the manuscript and M.I.D. assisted in it; O.F. and S.R.M.: critically reviewed the manuscript. All authors have gone through the manuscript and agree with its contents.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Diwan RK, Mehrotra N, Bindal U, Jethani SL, Kumar S. Bilateral congenital upper limb anomalies: a case report. J Anat Soc Ind 2009; 58 :44-46.  Back to cited text no. 1
    
2.
National Organization for Rare Disorders. Phocomelia syndrome. Available at: http://www.rarediseases.org. [Last accessed on 2014 Sep 10].  Back to cited text no. 2
    
3.
Shekokar SP, Shah T, Venkatesh S, Chandana C. Phocomelia: an extremely rare congenital disorder involving the limbs (dysmelia). Int J Fert and Fetal Med 2011; 2 :118-120.  Back to cited text no. 3
    
4.
Coodin FJ, Uchida IA, Murphy CH. Phocomelia: Report of Three Cases. Canad Med Ass J 1962: 87:735-739.  Back to cited text no. 4
    
5.
Lenz W. A short history of thalidomide embryopathy. Teratology 1988; 38 :203-215.  Back to cited text no. 5
    
6.
Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, et al.. Identification of a primary target of thalidomide teratogenicity. Science 2010; 327 : 1345-1350.  Back to cited text no. 6
    
7.
Galloway JL, Delgado I, Ros MA, Tabin CJ. A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning. Nature 2009; 460 :400-404.  Back to cited text no. 7
    
8.
Chakre GS, Chakre SU, Kulkarni PR. Phocomelia syndrome - a case report. JKIMSU 2012; 1 :150-151.  Back to cited text no. 8
    
9.
Moore KL, Persaud TVN, Torchia MG. The Musculoskeletal System. In Textbook of Essentials of Embryology and Birth Defects. John F. Kennedy (Ed). 7th Ed. Philadelphia, PA; 2008: 248.  Back to cited text no. 9
    
10.
Lenz W. Genetics and limb deficiencies. Clin Orthop Relat Res 1980; 148 :9-17.  Back to cited text no. 10
    
11.
Toriello HV. Thrombocytopenia Absent Radius Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. 2009 [Updated 2014 May 29]. (Pubmed).  Back to cited text no. 11
    
12.
Gordillo M, Vega H, Jabs EW. Roberts Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. 2006 [Updated 2013 Nov 14]. (Pubmed).  Back to cited text no. 12
    
13.
Aviña-Fierro JA, Colonnelli-Barba G. Holt-Oram syndrome associated with facial anomalies. A case report. Rev Med Inst Mex Seguro Soc 2010; 48 :657-659.  Back to cited text no. 13
    


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