Phocomelia

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“Phocomelia”

Student: zahra masoudi


student ID: 9518104574
Article Author
Donald D. Davis
Article Editor:
Steven M. Kane
Continuing Education Activity

Phocomelia is a rare congenital anomaly where the proximal aspect of an extremity is absent with the
hand or foot attached directly to the trunk. This disorder was brought into prominence as a
characteristic side effect of the drug thalidomide but can occur spontaneously. This activity seeks to
summarize the topic of phocomelia and examine the etiology and epidemiology of this disorder.
Furthermore, we seek to review the role of the interdisciplinary health team in optimizing the
management of this condition.

Objectives:

Identify the possible etiologies of phocomelia.


Outline the appropriate steps for the evaluation of phocomelia.
Review the management options available for phocomelia.
Describe the interprofessional team strategies for improving care coordination and communication to
advance phocomelia and improve outcomes.
Introduction

Phocomelia is a rare congenital defect defined by the absence of intermediate segments of the
extremity. Children with phocomelia present with their hands or feet directly attached to the trunk.
Phocomelia is famously a teratogenic side effect of the drug "thalidomide," a drug first marketed to
treat anxiety and morning sickness. Despite claims that the drug was safe during pregnancy, it was
removed from the market in the 1960s when clinicians noted an association with phocomelia. Forty
percent of patients affected by the teratogenic effects of thalidomide died near the time of birth. These
congenital disabilities had a profound social and political impact on drug regulation and proof of safety.
[1][2]

Etiology

While phocomelia is the most notable side effect of thalidomide, there have been several cases in the
last 30 years of phocomelia associated with thalidomide use. However, today the cause of most cases is
undetermined. Despite strict regulation worldwide, there have been several cases in the last 30 years of
thalidomide attributed phocomelia. Underdeveloped countries and those endemic with leprosy where
thalidomide occasionally remains in use, still report cases of defects caused by thalidomide exposures in
pregnancy. Strict regulations in more developed countries have resulted in a dramatically decreased
incidence of phocomelia within the general population.[3][4]

Aside from the teratogenicity of thalidomide, researchers have hypothesized that phocomelia is
associated with anomalous origins of the subclavian artery, resulting in a disrupted vascular supply to
intermediate limb segments.[5][6]
Epidemiology

The incidence and presentation of phocomelia were examined in 22,740,933 live births by Bermejo-
Sanchez et al. in an effort to assess the prevalence of true phocomelia. Reports indicate that true
phocomelia occurs in 0.62 live births per every 100,000 patients. Approximately half (53.2%) of the cases
displayed isolated phocomelia, while 36.9% had additional major congenital abnormalities, and 9.9% of
cases correlated with a clinical syndrome.

The data shows that 55.9% of cases only involve one limb, while 40.2% of cases only involved two limbs.
Only four cases of 141 had involvement of all four limbs. When comparing single upper extremities
deficiencies, the left side was more commonly affected (64.9%) than the right.

When two limbs were involved, the upper limbs were involved 58.5% of the time compared to the lower
limbs. The incidence of these findings was lower than what prior studies had reported, which is likely
due to the care taken by this study, only to consider true phocomelia and not amelia or other limb
truncation.[1][7]

Pathophysiology

In extremity development, the apical ectodermal ridge forms at the most distal end of the limb bud. This
apical ectodermal ridge through its interaction with the underlying progress zone mesoderm
subsequently determines appropriate longitudinal growth of the extremity, as well as differentiation of
distal and proximal structures of the limb bud. Cell death due to apoptosis from any cause such as
vascular insufficiency or drug toxicity that interrupts this relationship between the apical ectodermal
ridge and the progress zone can result in phocomelia.[8]

History and Physical

Any time phocomelia is identified in a newborn, and given its correlation with thalidomide, practitioners
should inquire about medications taken during early pregnancy. Additionally, children should undergo a
thorough physical examination as one study reported that 36.9% of phocomelia cases have additional
major malformations, with 9.9% of cases being attributable to various syndromes.[1]

Evaluation

When phocomelia is identified in a child, physicians should complete a thorough search for other
associated abnormalities, as other defects are present in approximately half of the patients presenting
with this limb anomaly. Particularly, practitioners should examine the musculoskeletal system, including
the vertebrae, the intestines, and the heart, as dysfunction in these organ systems appears most
frequently in conjunction with phocomelia.[1]

Treatment / Management

The most important management of a child born with phocomelia is to assess for other associated
abnormalities, especially of the heart and intestines, and address them promptly and appropriately.
Pediatric cardiologists and gastroenterologists should examine the child and recommend a treatment
plan for any abnormalities encountered.
From the perspective of the hypoplastic limb, prosthetics may be of some use, but many without
concomitant pathology can function quite well. Families of children who have severely hypoplastic
extremities should work with therapists to help understand how to meet the unique needs of their
children. And finally, caring for a disabled child can be traumatic for some people. Therefore, physicians
should have a low threshold to recommend mental counseling services to assist in coping mechanisms
that may be needed by both the parents and the child.

Differential Diagnosis

Bermejo-Sanchez et al. report that 9.9% of cases of phocomelia are associated with different syndromes.
They appear here in order of decreasing prevalence[1]:

Roberts Syndrome: A rare autosomal recessive disorder caused by a mutation in the ESCO2 gene that
manifests with severe limb malformations and craniofacial defects.[9]

Thrombocytopenia with radial aplasia (TAR): A rare autosomal recessive disorder related to the RBM8A
gene that presents with thrombocytopenia and limb radial deficiency.[10]

Syndrome of severe limb defects, vertebral hypersegmentation, and mirror polydactyly: An autosomal
recessive disorder resulting in severe limb hypoplasia with polydactyly and hypersegmentation of the
spine.[11]

Prognosis

In one review study, there were 85 live births to every 24 stillbirths for children with phocomelia. When
considering only cases of isolated phocomelia, there were 57 live births to every eight stillbirths.[1]

Complications

Children with phocomelia have a high stillbirth rate compared to the general population. Furthermore,
children with severe limb hypoplasia may or will face problems with activities of daily life and mobility.
For this reason, health care teams must be integrated to provide for more than just the medical
challenges that present with phocomelia.

Deterrence and Patient Education

Increased drug regulatory practices across the world have significantly decreased the incidence of
thalidomide-induced limb hypoplasia. Thalidomide has utility in the treatment of insomnia, anxiety, and
even in the treatment of leprosy, but understanding the risks of thalidomide exposure during pregnancy
is critical for any woman taking the medication. Patients and prescribers alike should understand the
deleterious effects of thalidomide when taken in early pregnancy.

Enhancing Healthcare Team Outcomes

Phocomelia and the thalidomide controversy was a critical step forward in the regulatory practices of
pharmacology. The most important responsibility of the healthcare community, regarding phocomelia,
is the prevention of prescribing unsafe medications that can cause limb truncation; this occurs through
careful prescribing practices and thorough patient education.
For patients born with limb hypoplasia, as is seen in phocomelia, an interdisciplinary team of specialists
needs to examine the patient to screen for associated abnormalities that may be fatal, as half of the
patients with phocomelia and amelia have associated defects. As many related abnormalities of the
heart, vertebrae, or other vital organs may be life-threatening, these anomalies should be addressed
promptly by consulting physicians. If surgical intervention is required, a dedicated OR team, including a
nurse, scrub technician, and surgical assists, must be well-versed in any operative plan and work
efficiently as a team to optimize patient outcomes.

Finally, a prosthetist and therapist can help a developing child with disabilities to function at a higher
level. Families caring for disabled children are often under tremendous financial and emotional strain.
Therefore, appropriate mental health counseling and social work may be necessary for caring not only
for the patient but for their families as well. [Level 5]

References

[1]

Bermejo-Sánchez E,Cuevas L,Amar E,Bianca S,Bianchi F,Botto LD,Canfield MA,Castilla EE,Clementi


M,Cocchi G,Landau D,Leoncini E,Li Z,Lowry RB,Mastroiacovo P,Mutchinick OM,Rissmann A,Ritvanen
A,Scarano G,Siffel C,Szabova E,Martínez-Frías ML, Phocomelia: a worldwide descriptive epidemiologic
study in a large series of cases from the International Clearinghouse for Birth Defects Surveillance and
Research, and overview of the literature. American journal of medical genetics. Part C, Seminars in
medical genetics. 2011 Nov 15; [PubMed PMID: 22002800]
[2]

Ridings JE, The thalidomide disaster, lessons from the past. Methods in molecular biology (Clifton, N.J.).
2013; [PubMed PMID: 23138926]
[3]

Castilla EE,Ashton-Prolla P,Barreda-Mejia E,Brunoni D,Cavalcanti DP,Correa-Neto J,Delgadillo JL,Dutra


MG,Felix T,Giraldo A,Juarez N,Lopez-Camelo JS,Nazer J,Orioli IM,Paz JE,Pessoto MA,Pina-Neto
JM,Quadrelli R,Rittler M,Rueda S,Saltos M,Sánchez O,Schüler L, Thalidomide, a current teratogen in
South America. Teratology. 1996 Dec; [PubMed PMID: 9098920]
[4]

Schuler-Faccini L,Soares RC,de Sousa AC,Maximino C,Luna E,Schwartz IV,Waldman C,Castilla EE, New
cases of thalidomide embryopathy in Brazil. Birth defects research. Part A, Clinical and molecular
teratology. 2007 Sep; [PubMed PMID: 17676592]
[5]

van der Horst RL,Gotsman MS, Anomalous origin of the subclavian artery associated with phocomelia.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde. 1971 Dec 18; [PubMed
PMID: 5136042]
[6]
Bavinck JN,Weaver DD, Subclavian artery supply disruption sequence: hypothesis of a vascular etiology
for Poland, Klippel-Feil, and Möbius anomalies. American journal of medical genetics. 1986 Apr;
[PubMed PMID: 3008556]
[7]

Källén B,Rahmani TM,Winberg J, Infants with congenital limb reduction registered in the Swedish
Register of Congenital Malformations. Teratology. 1984 Feb; [PubMed PMID: 6701808]
[8]

Knobloch J,Rüther U, Shedding light on an old mystery: thalidomide suppresses survival pathways to
induce limb defects. Cell cycle (Georgetown, Tex.). 2008 May 1; [PubMed PMID: 18418038]
[9]

Ismail S,Essawi M,Sedky N,Hassan H,Fayez A,Helmy N,Shehab M,Farouk D,Elruby M,Otaify G,Eldarsh
A,Hosny L,Gaber K,Aboul-Ezz EHA,Ramzy MI,Mehrez MI,Hassib NF,Elhadidi SMA,Aglan MS,Temtamy SA,
ROBERTS SYNDROME: CLINICAL AND CYTOGENETIC STUDIES IN 8 EGYPTIAN PATIENTS AND MOLECULAR
STUDIES IN 4 PATIENTS WITH GENOTYPE/PHENOTYPE CORRELATION. Genetic counseling (Geneva,
Switzerland). 2016; [PubMed PMID: 30204960]
[10]

Al-Qattan MM, The Pathogenesis of Radial Ray Deficiency in Thrombocytopenia-Absent Radius (TAR)
Syndrome. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2016 Nov; [PubMed
PMID: 27981927]
[11]

Urioste M,Lorda-Sánchez I,Blanco M,Burón E,Aparicio P,Martínez-Frías ML, Severe congenital limb
deficiencies, vertebral hypersegmentation, absent thymus and mirror polydactyly: a defect expression of
a developmental control gene? Human genetics. 1996 Feb; [PubMed PMID: 8566956]

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