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End stage renal disease in a child with oral facial digital syndrome

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Hossein Emad Momtaz at Hamedan University of Medical Sciences
Hossein Emad Momtaz
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Background: Oral facial digital syndrome (OFDS) is the name of a group of congenital diseases with involvement of face, oral cavity, digits and other organs. Renal involvement in OFD may be in form of polycystic kidney disease. Case Presentation: This case report presents a patient with OFDS who developed end-stage renal disease (ESRD) at age of six without evidence of renal cyst in sonography. Conclusions: It may be recommended to evaluate and follow up renal function in children with cleft lip and cleft palate especially when they have other anomalies such as polydactyly and oral lesions considering possibility of OFDS.
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End stage renal disease in a child with oral facial digital
syndrome
www.nephropathol.com DOI: 10.15171/jnp.2018.58 J Nephropathol. 2018;7(4):293-295
Journal of Nephropathology
*Corresponding author : Hossein Emad Momtaz, Email: hemmtz@yahoo.com
Hossein Emad Momtaz*
Division of Pediatric Nephrology, Besat Hospital, Hamadan University of Medical Sciences, Hamadan, Iran
Case Report
ARTICLE INFO
Article type:
Case Report
Article history:
Received: 7 May 2018
Accepted: 10 July 2018
Published online: 19 August 2018
Keywords:
Oral facial digital syndrome
End stage renal disease
Children
Background: Oral facial digital syndrome (OFDS) is the name of a group of congenital
diseases with involvement of face, oral cavity, digits and other organs. Renal involvement
in OFD may be in form of polycystic kidney disease.
Case Presentation: This case report presents a patient with OFDS who developed end-stage
renal disease (ESR D) at age of six without evidence of renal cyst in sonography.
Conclusions: It may be recommended to evaluate and follow up renal function in children
with cleft lip and cleft palate especially when they have other anomalies such as polydactyly
and oral lesions considering possibility of OFDS.
ABSTRACT
Implication for health policy/practice/research/medical education:
Renal involvement should be considered in all patients with multiple organ anomalies, especially in patients with cleft lip, cleft
palate and polydactyly. Absence of renal cysts does not exclude kidney involvement and further follow up of patient’s growth,
urine specific gravity, renal function and other sonographic findings such as renal echogenicity may be helpful.
Please cite this paper as: Emad Momtaz H. End stage renal disease in a child with oral facial digital syndrome. J Nephropathol.
2018;7(4):293-295. DOI: 10.15171/jnp.2018.58.
1. Background
Oral facial digital syndrome (OFDS) is the name of a
group of rare congenital diseases characterized by typical
malformations of face, oral cavity and digits. Renal
involvement in OFDS has been described mainly as
polycystic kidney disease that usually results in end-stage
renal disease (ESRD) in adulthood. This patient with
OFDS developed ESRD at age of six without evidence
of renal cyst in sonography.
2. Case Presentation
The patient is a 6-year-old boy with history of several
hospital admissions for aspiration pneumonia because of
cleft lip and cleft palate since early infancy, this time he
was scheduled to be operated for multiple tongue masses.
On physical examination he had short stature (height
= 93 cm/< 3 percentile/-4.4SD), flat nasal bridge,
multiple masses of tongue( Figure 1), prominent skull
(due to hydrocephaly) and polydactyly of hands. Blood
pressure was normal (Figure 2). Pre-operative evaluation
showed; hemoglobin = 7.3 g/dL, blood urea nitrogen
(BUN) = 36 mg/dL, creatinine = 3 mg/dL, K = 5.7,
mEq/L, pH = 7.3 ad HCO3 = 17.4 mmol/L. Urinalysis
showed specific gravity of 1.005, +1 proteinuria and
+1 glycosuria. In renal sonography patient had bilateral
echogenic kidneys. Estimated glomerular filtration rate
(GFR) (calculated by modified Schwartz’s formula) was
12.8 cc/min/1.73 m2. Due to significant rise of serum
creatinine, continuous ambulatory peritoneal dialysis
(CAPD) was started for patient and he is candidate for
renal transplantation now.
3. Discussion
OFDS is the name of a group of rare congenital diseases
ID
Emad Momtaz H
Journal of Nephropathology, Vol 7, No 4, October 2018 www.nephropathol.com
294
characterized by typical malformations of face, oral
cavity and digits. The first description of this syndrome
was conducted by “Mohr” in 1941 who reported patients
with distinct features of lobulated tongue, hypertelorism,
high arched palate and broad nasal bridge (1). Since
then 11 types of OFDS have been described. Two of
those types (OFDS I and OFDS IV) are associated with
miscellaneous phenotypes and organ involvements that
could overlap with each other in some presentations.
OFDS type I is the most frequent type with estimated
incidence of 1:50 000 – 1:250 000 live births (2). It may
occur in 1.5:1000 patients with cleft lip, cleft palate or
both. Seventy-five percent of OFDS1 is sporadic. X
linked dominant inheritance pattern is lethal in males
(3). Other types of OFDS except type VIII (X linked)
are transmitted as autosomal recessive trait. OFDS 1 is
caused by mutation of OFD I gene located on XP22.2-
22.3 (4). This gene is recognizable in 85% of patients
with OFD1 phenotype. OFDS I gene is a component of
distal centriole (5), and is responsible for production of
a protein present in structure of both primary cilium and
nucleus. Hence, we can consider OFD1 as a member of
“ciliopathies” family (6).
Renal involvement in OFD has been described in
Figure 2. Polydactyly of hands in .in our patient with oral facial
digital syndrome.
Figure 1. Multiple tongue masses in our patient with oral facial
digital syndrome. Note scar of previous surgery for cleft lip and
cleft palate.
types I , III, IV, VI and VII (7). Major form of renal
involvement in OFDS is polycystic kidney disease (8).
Renal Cysts may be detected from neonatal period and
childhood but more commonly are discovered in early
adulthood. In one study frequency of polycystic kidney
disease was around 35% (9). Another study showed
that, 16% of cysts presented below 18 years of age and
63% after 18 years of age(10). In spite of autosomal
dominant polycystic kidney disease (ADPKD), cysts
in OFDS I originate from glomeruli rather than renal
tubules. Additionally, size of cysts are not so large and
overall renal size is not enlarged as in ADPKD (2).
Renal insufficiency has been reported in OFDS primarily
due to polycystic kidney disease. Renal insufficiency
usually presents after 18 years of age (11). In one study
ESRD in two patients with 28 and 35 years of age was
regarded as early ESRD and authors recommended
monitoring of renal function in OFDS patients (12). In
one report renal failure was detected in an 11 year old girl
with OFDS type I (13).
In our case despite characteristic clinical findings of
OFDS, chronic kidney disease was not associated with
polycystic kidney disease but rather with increased renal
echogenicity and low urine specific gravity without
hypertension or hematuria. These findings are more
consistent with renal involvement in ciliopathies such as
nephronophthisis.
4. Conclusions
It may be recommended to evaluate and follow up
renal function in children with cleft lip and cleft palate
especially when they have other anomalies such as
polydactyly and oral lesions considering possibility of
OFDS.
Author’s contribution
The author passed all criteria for authorship contribution
based on recommendations of the International
Committee of Medical Journal Editors. HEM handled
the case and managed him, supervised the treatment,
prepared the primary draft, edited and finalized the
manuscript. The author read and signed the final paper.
Conflicts of interests
The authors declared no potential conflicts of interest
with respect to the case, authorship, and/or publication
of this article.
Ethical considerations
Ethical issues (including plagiarism, data fabrication,
www.nephropathol.com Journal of Nephropathology, Vol 7, No 4, October 2018
Oral facial digital syndrome
295
double publication) have been completely observed by
the author. Consent of patient was obtained for report.
Funding/Support
None.
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ResearchGate has not been able to resolve any citations for this publication.
An Atypical Presentation of a Male with Oral-Facial-Digital Syndrome Type 1 Related Ciliopathy
Article
Full-text available
  • Jan 2016
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View
Update on oral-facial-digital syndromes (OFDS)
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  • May 2016
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View
The Oral-Facial-Digital Syndrome Type 1 (OFD1), a Cause of Polycystic Kidney Disease and Associated Malformations, Maps to Xp22.2-Xp22.3
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Orofacial digital syndrome type 1: An underlying cause of chronic renal failure
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Fibrocystic Disease of Liver and Pancreas; Under-Recognized Features of the X-Linked Ciliopathy Oral-Facial-Digital Syndrome Type 1 (OFD I)
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  • Oct 2010
  • AM J MED GENET A
OFD I is an X-linked dominant male-lethal ciliopathy characterized by prominent external features including oral clefts, hamartomas or cysts of the tongue, and digital anomalies. Although these external features are easy to recognize and often lead to diagnosis in early childhood, visceral findings in OFD I, especially the fibrocystic liver and pancreas disease, are under-recognized. In addition, while the occurrence of polycystic kidney disease (PKD) in OFD I is well known, few patients are evaluated and monitored for this complication. We report on two adult females diagnosed with OFD I in infancy, but not evaluated for visceral involvement. In adulthood, they were incidentally found to have severe hypertension and chronic renal insufficiency due to undiagnosed PKD. A pancreatic cystic lesion, also discovered incidentally, was thought to be malignant and led to consideration of major surgery. We present NIH evaluations, including documentation of OFD I mutations, extreme beading of the intrahepatic bile ducts, pancreatic cysts, and tabulate features of reported OFD I cases having hepatic, pancreatic, and renal cystic disease. Liver and pancreas are not routinely evaluated in OFD I patients. Increased awareness and lifelong monitoring of visceral complications, particularly involving the liver, pancreas, and kidney, are essential for timely and accurate treatment.
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Ofd1, a Human Disease Gene, Regulates the Length and Distal Structure of Centrioles
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Centrosomes and their component centrioles represent the principal microtubule organizing centers of animal cells. Here, we show that the gene underlying orofaciodigital syndrome 1, Ofd1, is a component of the distal centriole that controls centriole length. In the absence of Ofd1, distal regions of centrioles, but not procentrioles, elongate abnormally. These long centrioles are structurally similar to normal centrioles but contain destabilized microtubules with abnormal posttranslational modifications. Ofd1 is also important for centriole distal appendage formation and centriolar recruitment of the intraflagellar transport protein Ift88. To model OFD1 syndrome in embryonic stem cells, we replaced the Ofd1 gene with missense alleles from human OFD1 patients. Distinct disease-associated mutations cause different degrees of excessive or decreased centriole elongation, all of which are associated with diminished ciliogenesis. Our results indicate that Ofd1 acts at the distal centriole to build distal appendages, recruit Ift88, and stabilize centriolar microtubules at a defined length.
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Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I
Article
Saal S, Faivre L, Aral B, Gigot N, Toutain A, Van Maldergem L, Destree A, Maystadt I, Cosyns J‐P, Jouk P‐S, Loeys B, Chauveau D, Bieth E, Layet V, Mathieu M, Lespinasse J, Teebi A, Franco B, Gautier E, Binquet C, Masurel‐Paulet A, Mousson C, Gouyon J‐B, Huet F, Thauvin‐Robinet C. Renal insufficiency, a frequent complication with age in oral‐facial‐digital syndrome type I. The oral‐facial‐digital syndrome type I (OFD I) is characterized by multiple congenital malformations of the face, oral cavity and digits. A polycystic kidney disease (PKD) is found in about one‐third of patients but long‐term outcome and complications are not well described in the international literature. Renal findings have been retrospectively collected in a cohort of 34 females all carrying a pathogenic mutation in the OFD1 gene with ages ranging from 1 to 65 years. Twelve patients presented with PKD – 11/16 (69%) if only adults were considered –with a median age at diagnosis of 29 years [IQR (interquartile range) = (23.5–38)]. Among them, 10 also presented with renal impairment and 6 were grafted (median age = 38 years [IQR = (25–48)]. One grafted patient under immunosuppressive treatment died from a tumor originated from a native kidney. The probability to develop renal failure was estimated to be more than 50% after the age of 36 years. Besides, neither genotype‐phenotype correlation nor clinical predictive association with renal failure could be evidenced. These data reveal an unsuspected high incidence rate of the renal impairment outcome in OFD I syndrome. A systematic ultrasound (US) and renal function follow‐up is therefore highly recommended for all OFD I patients.
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