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Screening Procedure for 
Hemihypertrophy: Preliminary 
Results of International Multicenter 
Prospective Study 
 
Michael Vaiman1, Phillip Shilco2,9, Yulia Roitblat3, 

Nicolas Padilla-Raygoza4, Aidan Leit5, Aaron Kavin6, 

Edan Schonberger6, Liliia Nehuliaieva7, Noa 

Buchris8,9, Michael Shterenshis9 
 
1Department of Otolaryngology, Assaf Harofeh Medical Center, 

Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel-

Aviv, Israel; 
2“Briut HaShen” Dental Health Clinic, Jerusalem, Israel   

3Department of Sciences, Belkind School for Special Education, 

Rishon-LeZion, Israel; 
4Department of Nursing and Obstetrics, Division of Health Sciences 

and Engineering, Campus Celaya-Salvatierra, University of 

Guanajuato, Mexico; 
5Department of Sciences, The Harley School, Rochester, NY, USA; 

6Department of Anatomy, Mount Moriah College, Sydney, Australia; 
7Department of Pediatrics, Danylo Halytsky Lviv National Medical 

University, Lviv, Ukraine;  
8Dept. of Sciences, El Camino Real Charter High School, Woodland 

Hills, CA, USA; 

9Science Research Department, Alexander Muss High School in 

Israel (AMHSI) affiliated with Alexander Muss Institute for Israel 

Education (AMIIE), Hod HaSharon, Israel 

Vol. 8, No. 1 (2019)   |   ISSN 2166-7403 (online)  
DOI 10.5195/cajgh.2019.336 |   http://cajgh.pitt.edu 

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Central Asian Journal of Global Health 
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Abstract 

Introduction: Isolated or congenital hemihypertrophy is a rare disorder characterized by asymmetric overgrowth of one side of 
the body. This article describes the protocol and preliminary results of a lateral body asymmetry (hemihypertrophy) screening 
procedure performed in healthy adolescents in a multicenter study. The reported incidence of hemihypertrophy varies between 
different publications and standardized protocols are needed to improve research in this area. 
Methods: Our screening program is taking place in Australia, Israel, Mexico, Ukraine and USA. Procedure includes two steps:  (1) 
“three measurements – three questions” screening, or assessment of face, palms, and shins; (2) in-depth assessment of selected 
cases in order to exclude localized, lesional, and syndrome-related cases as well as body asymmetry within normative range and to 
select suspected cases of isolated hemihypertrophy. This step includes measurements of various anatomical regions and a detailed 
questionnaire. 
Results: At this stage, the screening procedure is completed and the selected participants are advised to refer to medical institutions 
for further clinical and genetic follow up to exclude possible tumors and other accompanying disorders. 
Conclusion: We present an easy-to-use selection tool to identify children with suspected IH, which results in the selection of the 
risk group that may benefit from referral to a pediatrician and a clinical geneticist. 

Keywords: Hemihypertrophy; Hemihyperplasia; Asymmetric regional body overgrowth; Body asymmetry; Adolescents 

Screening Procedure for 
Hemihypertrophy: Preliminary Results of 
International Multicenter Prospective 
study 
 
Michael Vaiman1, Phillip Shilco2,9, Yulia Roitblat3, Nicolas 

Padilla-Raygoza4, Aidan Leit5, Aaron Kavin6, Edan 

Schonberger6, Liliia Nehuliaieva7, Noa Buchris8,9, 

Michael Shterenshis9 
 
1Department of Otolaryngology, Assaf Harofeh Medical Center, Affiliated 

with Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel; 
2“Briut HaShen” Dental Health Clinic, Jerusalem, Israel   

3Department of Sciences, Belkind School for Special Education, Rishon-

LeZion, Israel; 
4Department of Nursing and Obstetrics, Division of Health Sciences and 

Engineering, Campus Celaya-Salvatierra, University of Guanajuato, 

Mexico; 
5Department of Sciences, The Harley School, Rochester, NY, USA; 

6Department of Anatomy, Mount Moriah College, Sydney, Australia; 
7Department of Pediatrics, Danylo Halytsky Lviv National Medical 

University, Lviv, Ukraine;  

8Dept. of Sciences, El Camino Real Charter High School, Woodland Hills, 

CA, USA; 

9Science Research Department, Alexander Muss High School in Israel 

(AMHSI) affiliated with Alexander Muss Institute for Israel Education 

(AMIIE), Hod HaSharon, Israel 

Research 

Introduction 

Isolated or congenital hemihypertrophy (IH, 
isolated hemihyperplasia, Human Genetic Disorders 
Code: OMIM 23500; lateralized overgrowth) is a rare 
disorder characterized by asymmetric overgrowth of one 
side of the body. Statistics vary on how many people 
actually have this pathology because the incidence of IH 
has been reported to range from 1:13,000 to 1:86,000 live 
births.1 Such estimation may be inaccurate, as the age of 
onset of IH can vary between the cases. Numerous case 
reports describe patients who were first referred to a 
pediatrician between 10 and18 years of age.2-4  

In general, patients with IH are at an increased 
risk for medullary sponge kidneys, arteriovenous 
abnormalities, and tumors in the abdomen. Therefore, 

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CENTRAL ASIAN JOURNAL OF GLOBAL HEALTH 
 

 

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of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 
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having a standardized screening procedure for such cases 
is desirable.5,6 Adolescents are not usually at risk for 
tumor development, yet some internal abnormalities may 
accompany visible body asymmetry, which may severely 
affect quality of adolescents’ life.1,2,7 Diagnosing IH is 
complicated by similar  conditions, including Beckwith-
Wiedemann syndrome, Proteus syndrome, Klippel-
Trenaunay syndrome, and Sotos syndrome, which have 
symptoms similar to IH. Most of these disorders are 
presented at birth or identified in early childhood, thus 
the main purpose of the screening is to detect IH in older 
children.  

This study describes a screening procedure and 
the selection tool for adolescent IH cases. Recently 
published article by Mark et al. describes in detail how a 
practitioner should assess and investigate a patient with 
suspected IH and what surveillance strategy should be 
applied to such patients.8 Our screening procedure may 
help to select potential IH cases that may benefit from 
such fifteen-minute consultation. This article describes 
the protocol and preliminary results of a lateral body 
asymmetry (hemihypertrophy) screening procedure 
performed in healthy adolescents in a multicenter study.  

 

Screening procedure  

Study population  

Our screening is currently taking place in 
several countries including USA, Australia, Israel, 
Mexico, and Ukraine, aiming to screen at least 5000 
participants in each country. Institutional Review Board 
approvals were acquired for each respective institution 
that conducts this research. Inclusion criteria were the 
following: healthy individuals, aged 15-18, of both sexes. 
Exclusion criteria were the following: individuals with 
known disorders such as Beckwith-Wiedemann 
syndrome, mosaic trisomy 8, Proteus syndrome, Russell-
Silver syndrome (hemihypotrophy), Klippel-Trenaunay 
syndrome, Sotos syndrome, neurofibromatosis Type 1, 
and Bannayan-Riley syndrome. Prospective participants 
were excluded from the study if their body asymmetry 
was a result of known trauma, lymphatic 
malformation/lymphedema, and vascular malformations. 

Initial screening  

The screening procedure includes two steps. 
The initial step is “three measurements – three questions” 
screening, or “face – palms – shins survey”. The three 
measurements are:  

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1. The measurement of the fullest part of the calf 
below the knee with a difference of 
circumference ˃1.5 cm between the two legs 
reported as significant,  

2. Comparison of palms (Figure 1a), with a 
difference of length ˃1 cm between the two 
hands reported as significant, 

3. Assessing face asymmetry by measuring the 
distance between philtrum (below the nose) and 
the angle of a lower jaw (Figure 1b) with a 
difference of width ˃1.5 cm as significant. 

Each participant is asked the following three 
questions: 

1. Is he/she bothered with his/her body 
asymmetry?  

2. Has he/she ever had dental braces, orthodontic 
treatment, lower jaw repositioning, etc.  

3. Has he/she ever visited a podiatrist, had 
orthopedic treatment, or worn shoes of different 
sizes?   

The total score for a participant after all measurements 
and answers ranges from 0 to 9. Each positive answer to 
the question adds 1 point; each asymmetrical 
measurement adds 1 point if the asymmetry does not 
psychologically bother a participant, and 2 points if the 
asymmetry is reported as bothersome to a participant. 
The selection for the second step is based on the 
assessment of the score: score 0 to 2 – definitely not 
selected, score 4 to 9 – definitely selected, score 3– 
selected if all three points were gained from the 
measurements data. About five minutes per participant 
are needed to complete this stage of assessment. 

Follow-up screening 

The subsequent step is in-depth assessment of 
selected cases to select suspected cases of IH and exclude 
localized or lesional cases, in which initial findings are 
not supported by anatomical changes in other parts of the 
body or the history of trauma is present. This step 
includes measurements of various anatomical regions 

(length of the soles, legs and arms, the circumference of 
the thigh 10 cm above the upper edge of the patella, 
theleft and right half-circumferences from the navel to 
the spinous process of L4, presence/absence of scoliosis). 
Each additional asymmetrical measurement (˃1.5 cm as 
significant) adds 1 point to the score. An additional 
question is asked: “Are there any other members of your 
family with any kind of body asymmetry?” A positive 
answer adds 3 points to the score. The subsequent 
questions concern the type of malignancy in the family 
(yes/no, which type, if yes – 1 point is added; if Wilms 
tumor (nephroblastoma that is usually diagnosed in 
children under the age of 6) – 3 points are added), and 
ultrasonography of the abdomen (performed: yes/no, if 
no - 1 point is added). If three or more points are added 
to the initial score that a participant obtained at the first 
stage, the participant is assigned to the risk group. About 
10-15 minutes per participant are needed for these 
measurements and questions.  

At this stage, the screening procedure ends and 
the selected participants, “the risk group”, are advised to 
refer to medical institutions for further investigations to 
confirm/disprove IH, for differential diagnosis between 
hemihypertrophy and hemihypotrophy, that may involve 
further investigations, and to exclude possible 
accompanying disorders. 

 

Results and Discussion 

The preliminary findings as for December 2018 
are presented in Table 1. These findings indicate the 
incidence of IH as 1:5000 that is significantly higher than 
previous 1:13,000 to 1:86,000 estimates. While the initial 
genetic mutation that leads to IH and the subsequent 
syndromes appeared in Europe in the 19th century, it was 
rapidly spreading over the planet in the20th century and 
became a global phenomenon in the 21st century.1,4,6-8  

The above-described screening procedure is 
taking place using the protocol described above in several

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Country   Goal  # of participants  Selected for Selected for Diagnosis was 
      Screened    Stage 2  “Risk group” confirmed  

Australia  5000   478    2   1  0 
Israel   5000   5000    185   41  1 
Mexico   5000   370    0   0  0 
Ukraine   5000   1834    4   2  0 
USA   5000   2384    76   29  1 

Total   25,000  10,066   267   73  2 

Table 1. Preliminary results of the research (for December 2018) country by country included in the survey. 
 

countries across various continents. We would like to 
suggest that a higher number of children and adolescents 
with suspected IH need to be referred to pediatricians for 
consultation to confirm or rule out the disorder in order 
to improve quality of life of the patients and to ensure that 
no internal anatomical changes, such as possible 
accompanying hyperplasia/hypertrophy of the abdominal 
organs, are evolving. Recently published preliminary 
results based on 6000 participants9 estimate the incidence 
of IH ranging from 1:13,000 to 1:86,0001 is an 
underestimation. Our goal, therefore, is to screen 25,000 
participants internationally to estimate global prevalence 
of the disorder. Our preliminary assessment corroborates 
the findings of Schook et al.10 These authors investigated 
170 children with a referral diagnosis of lower extremity 
lymphedema. They confirmed this diagnosis in only 72.9 
percent of patients and found IH in 8.7 percent of the 
initial cohort.  These important findings indicate that IH 
can be overlooked or misdiagnosed which may lead to 
incorrect management of some patients.   

The rationale for selecting the first step 
measurements was based on the fact that IH most often 
reveals itself through facial hemihypertrophy and 
hypertrophy of the limbs. The 1.5 cm difference was 
chosen as significant because most study participants had 
left-right face and shins asymmetry between 0.5 and 1.5 
cm.9 The length of the palms, however, was symmetrical 

in most of the cases. The first question was chosen to 
assess the quality of life and psychological issues. The 
second question probes further into the facial asymmetry. 
Misdevelopment of the lower jaw is a significant 
indicator of IH. IH is associated with dental and oral 
abnormalities, including dental arch asymmetry and 
differences of dental development in the right and left 
jaws.11,12 Maxillo-facial surgeons may approach the case 
as an isolated pathology and IH can be overlooked. The 
same is true for the feet. For abnormal limb size, 
orthopedic treatment and corrective shoes can be 
recommended as palliative measures, but podiatrists may 
overlook IH. 

The subsequent steps will aim to collect more 
data within the survey frame. While numerous reports on 
genetic abnormalities in IH cases were published, 
additional assessment of other family members to rule 
out any kind of body asymmetry may be highly 
informative because hereditary basis of the disorder, the 
instability of the 11p15.5 chromosomal region, is very 
well established.1-5,8-10 A close connection between IH 
and Wilms tumor (nephroblastoma, a common pediatric 
neoplasm of the kidney) was postulated already in the 
1950s and was confirmed in more recent 
publications.13,14 While the overall median age for Wilms 
tumor is 3.5 years, adolescents and even adults also can 
be affected.15,16 That is why the question about Wilms 

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tumor is one of the key questions in the questionnaire, 
despite the fact that tumor risk for adolescents is low.  

We present an easy-to-use selection tool to 
identify subjects with suspected IH who may benefit 
from further clinical investigation and genetic 
counseling. The selection tool involves anthropological 
measurements and questions concerning family history, 
quality of life, and details of the lateral body asymmetry, 
which results in the selection of the risk group that may 
benefit from referral to a pediatrician and a clinical 
geneticist. 

 

Acknowledgements  

The authors thank Mordechai Cohen, Orit 
Rome, Leor Sinai, and Rachelle Sevitt for assistance with 
this research in Israel; Ryan Cleminson and Caleb 
Crossley for assistance with this research in Australia; 
Xóchitl Sofía Ramírez Gómez, Cuauhtémoc Sandoval 
Salazar, Marissa Padilla Morales for assistance with this 
research in Mexico; and Jacob Ilani, Jacob Burger, Jacob 
Hanai, and Sari Rosenberg for assistance with this 
research in the USA. 

 

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https://www.ncbi.nlm.nih.gov/pubmed/?term=Sun%20XH%5BAuthor%5D&cauthor=true&cauthor_uid=16285549
https://www.ncbi.nlm.nih.gov/pubmed/16285549
https://www.ncbi.nlm.nih.gov/pubmed/16285549
https://www.ncbi.nlm.nih.gov/pubmed/13292237
https://www.ncbi.nlm.nih.gov/pubmed/13292237
https://www.ncbi.nlm.nih.gov/pubmed/23970395
https://www.ncbi.nlm.nih.gov/pubmed/23970395

	Abstract
	Keywords: Hemihypertrophy; Hemihyperplasia; Asymmetric regional body overgrowth; Body asymmetry; Adolescents
	Research

