Journal of Advanced Biochemistry

 

Van Lohuizen Syndrome, A Late-Diagnosed Case in an 18 Years-Old Female: Case Report in Orthopaedic Research Clinical Trials in Orthopaedic Surgery

Abdulrahim Aljayar1, Dario Furnari1*ORCID ID, James Stoxen2, Khaled Hamlaoui1, Nadya Khan3 and Charlie Peebles4

1 Department of Biomedical Sciences, St. Magnus Hospital, United Kingdom

2 Department Aljayar Clinic, Benghazi, Libya

3Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates

4Indiana State University, Indiana

*Corresponding Author: Furnari D, Department of Biomedical Sciences, St. Magnus Hospital, United Kingdom. E-mail:  [email protected]

Citation: Aljayar A, Furnari D, Stoxen J, Hamlaoui K, Khan N et al. Van Lohuizen Syndrome, A Late-Diagnosed Case in an 18 Years-Old Female: Case Report in Orthopaedic Research Clinical Trials in Orthopaedic Surgery. Journal of Advanced Biochemistry. 2021;1(2):1-7.

 

Copyright: © 2021 Furnari D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received On: 11th October, 2021     Accepted On: 15th October, 2021    Published On: 25th October, 2021

Abstract

Cutis Marmorata Telangiectatica Congenita (CMTC) is a very rare birth defect involving cutaneous blood vessels. Of unknown cause, uncertain pathophysiology, unclear epidemiology. Described as a localized, or generalized marbled skin appearance (cutis marmarota), in addition to the skin, it may involve any other body organs, with, or without a wide variety of associated congenital anomalies. Kato van Lohuizen described the first case in 1922. Since then, there have been less than 300 cases reported worldwide to date. We are adding one more case, and the first reported in Libya.  

Keywords: Cutis marmorata, Telangiectasia, Port-wine Stains

Introduction

Van Lohuizen Syndrome, or Cutis Marmorata Telangiectatica Congenita. Is a very rare birth defect involving the cutaneous blood vessels, often reported as a benign, congenital disorder of unknown etiology, epidemiology, and pathophysiology. Described as persistent cutaneous telangiectasia, and phlebectasia, these appear as reticulated streaks of the skin capillaries and venules, resulting in a marbled-looking skin (cutis marmarota) [1-3]. First described by Kato van Lohuizen, a female Dutch pediatrician, in 1922 [4]. Since then, it has been referred to under several names, including, congenital generalized phlebectasia, [5,6] naevus vascularis reticularis, [7] as well as congenital livedo reticulari [8]. Characterized by the presence of erythematous network streaks, without venectasia, which is not responding to local heating. It may occur along with port-wine stain, [9] cutaneous ulceration, and atrophy within the affected area, as well as body asymmetry, and may affect any organ, including the eyes, skeleton, kidneys, and the brain [10-12].  

Case report

We are reporting the first case of CMTC in Libya, in 18 years old girl referred to our clinic for consultation. She had persistent skin disorders in her Rt. upper limb since birth (Figure 1).

 

Figure 1. Cutis marmorata, Cutis marmorata, erythematous network of telangiectatic cutaneous capillaries.  

She is the third of three siblings, born as a full-term baby, by uncomplicated vaginal delivery, to a non-consanguineous marriage, and there was no family history of similar lesions. A high school student, leading a normal active life, until about a year ago, when she began to feel intermittently some discomfort and numbness of the right hand and forearm, with no history of trauma.  Her upper extremity skin changes were detected at birth along with contralateral DDH, which was treated conservatively.  

Our clinical findings revealed a network of blue-purple lines giving the skin a marbled appearance along the right upper extremity from the deltoid insertion to the metacarpophalangeal joints level dorsally, sparing the Palmer skin, otherwise, her skin temperature and texture were normal, without atrophy or ulceration (Figure 2).    


Figure 2. Tthe lesion extends along the right upper limb, between the deltoid insertion proximally and the Metacarpophalangeal joints level distally, sparing the phalangeal skin dorsally and the palmar skin volar.  

The lesions were fading at Direct pressure, but not affected by gravity. There were multiple irregularly shaped port-wine stain patches on the right ankle laterally, left leg posteriorly, and the right thigh anteromedially.  

 

Figure 3. Multiple irregularly shaped port-wine stain patches on the ankle A, leg B, and thigh C.  

No upper or lower limbs atrophy, circumferential, or length discrepancy, and her gait was normal, there was no scoliosis, or facial asymmetry.  There were no sensory or motor deficits detected clinically. Here skeletal survey, abdominal and pelvic ultrasound, echocardiography, and all laboratory investigations were within normal. Based on this medical history and clinical presentation, the diagnosis of Van Lohuizen syndrome was confirmed.  

Discussion

Van Lohuizen syndrome is a rare congenital disorder, with less than 300 cases reported worldwide to date [2,12.13]. However, since not all cases are diagnosed, it is difficult to determine incidence rates.

Its origin and gender prevalence are still obscure and unclear, although, it is believed by some to be prevalent among females (64%) [14,15]. In some rare cases, CMTC may run in families [11]. However, Amitai et al. observed no familial cases of CMTC in their series, and most of the cases seem to be sporadic, with no racial predilection [16]. However, skin biopsies have revealed genetic mutations in GNA11, [17, 20] and some researchers have also reported genetic mutations in ARL6IP6, suggesting its inheritance as a recessive trait [20-23]. Moreover, viral infections have been postulated, and the underlying connective tissue abnormality has been supposed.

Its diagnosis is clinically based. It appears as cutaneous erythematous reticulum streaks, fading upon direct local pressure but unaffected by local heating or gravity, with no Ven ectasia, findings that Kienast, [9] considered three of which as primary signs.  

While the presence of skin atrophy and ulceration, and the port-wine stains outside the areas affected by CMTC, have been considered a secondary diagnostic criterion (Table 1).

 

Major criterion

Minor criterion

Congenital reticulate erythema.

Fading of the erythema by time.

Absence of venectasia.

Cutaneous atrophy.

Not affected by local heating.

 

Cutaneous ulcerations.

 

Port-wine stain.

Table 1. The major and minor diagnostic criteria, Kienast classification [2].

For diagnosis, the presence of three major signs and two of the minor criteria is indicative [2]. In most cases (66.8%), the disorder is localized, and the lesions are unilateral in 65% of the cases, more frequently involving the limbs (69%) [16], where the upper limbs are affected in (25.9%), while the hands are involved in only (4.9%), but can be generalized in about (24.5%) of cases [24]. CMTC may involve any organ in the body, including the eyes, skeleton, brain, kidneys, and others [10]. The most frequently associated anomalies, in 18.8% of patients, [16] include body asymmetry, neurological, ophthalmological, and cardiovascular defects, dysmorphic features, genitourinary, and endocrinological defects [2, 16, 24-29].  

The CMTC should be distinguished from congenital livedo reticularis, which is caused by mosaic PIK3CA gene mutations, [30] where ulceration and phlebectomies do not occur, Sturge-Weber syndrome, which is caused by mosaic GNAQ gene mutations, [17] Neonatal lupus erythematosus, [31] and Klippel-Trenaunay syndrome.  

Although, histopathology may confirm the diagnosis by showing an increased number and size of capillaries and venules in the dermal layer, endothelial swelling, and sometimes aneurysms, it is not necessary, and nonspecific [16, 32-35]. Imaging, and fluorescein angiography are indicated only for the evaluation of other congenital anomalies that may accompany the CMTC. Up to the moment, there is no definitive treatment for skin symptoms in CMTC. However, sympathectomy, and laser therapy are postulated [14, 32, 34-38].

In our current case, we believe that treatment is unnecessary, apart from reassurance and may be a psychological support to ease the burden of the aesthetic appearance, for although the problem involves a wide area of about (9%) of the total body surface area (TBSA), [39, 40] it is still localized, and it is without any other associated problem apart from the described port-wine patches. She is a tertiary school student, living a normal life with no functional or intellectual issues.

However, if we consider her complaint of discomfort and numbness as part of the problem or some of its long-term sequels, [40] the clinical findings and investigation results do not suggest more than the need for follow-up. Although some authors, including Kienast, state that skin lesions typically become less and often completely disappear by adolescence, [3, 4, 16] this is not the case with our patient [12, 40].

References

  1. Ozkur E, Altunay IK, Gur TF. What is your diagnosis? /Taniniz Nedir? Turkish Archives of Dermatology and Venereology. 2020 Sep 1;54(3):122-4.
  2. Kienast AK, Hoeger PH. Cutis marmorata telangiectatica congenita: a prospective study of 27 cases and review of the literature with proposal of diagnostic criteria. Clinical and Experimental Dermatology: Clinical dermatology. 2009 Apr;34(3):319-23. 
  3. Proietti I, Bernardini N, Balduzzi V, Marchesiello A, Zuber S, Mancini M, Petrozza V, Potenza C. Cutis Marmorata Telangiectatica Congenita: A Diagnostic Challenge. Giornale italiano di dermatologia e venereologia: organo ufficiale, Societa italiana di dermatologia e sifilografia. 2020 Feb;155(1):108-10. 
  4. Van Lohuizen CH. Uber eine seltene angeborene Hautanomalie (Cutis marmorata telangiectatica congenita). Acta Derm Venereol. 1922; 3:202-11.
  5. Kantor I, Yep D. Congenital generalized phlebectasia. InArchives of Dermatology 1966 Jan 1 (Vol. 93, No. 6, p. 774). 515 N STATE ST, CHICAGO, IL 60610: AMER MEDICAL ASSOC.
  6. Lynch PJ, Zelickson AS. Congenital phlebectasia: a histopathologic study. Archives of dermatology. 1967 Jan 1;95(1):98-101. 
  7. Brain RT. Naevus vascularis reticularis (two cases). 
  8. Champion RH. Livedo reticularis. A review. British Journal of Dermatology. 1965 Apr;77(4):167-79.
  9. Rupprecht R, Hundeiker M. Cutis marmorata teleangiectatica congenita Wichtige Aspekte für die dermatologische Praxis. Der Hautarzt. 1997 Jan;48(1):21-5. 
  10. Powell ST, Su WP. Cutis marmorata telangiectatica congenita: report of nine cases and review of the literature. Cutis. 1984 Sep 1;34(3):305-12. 
  11. Sybert VP. Genetic skin disorders. Oxford University Press; 2017 Jan 2. 
  12. Jia D, Rajadurai VS, Chandran S. Cutis marmorata telangiectatica congenita with skin ulceration: a rare benign skin vascular malformation. Case Reports. 2018 Oct 5;2018: bcr-2018.
  13. Putkowski S. The National Organization for Rare Disorders (NORD) Providing Advocacy for People with Rare Disorders. NASN school nurse. 2010 Jan;25(1):38-41. 
  14. Elzouki AY, Harfi HA, Nazer H, Oh W, Stapleton FB, Whitley RJ. Textbook of clinical pediatrics. Springer Science & Business Media; 2011 Oct 29.
  15. Pielop JA, Levy ML. Vascular lesions and congenital nevi in the newborn. UpToDate Online. 2005;13.
  16. Amitai DB, Fichman S, Merlob P, Morad Y, Lapidoth M, Metzker A. Cutis marmorata telangiectatica congenita: clinical findings in 85 patients. Pediatric dermatology. 2000 Mar;17(2):100-4. 
  17. Happle R. Capillary malformations: a classification using specific names for specific skin disorders. Journal of the European Academy of Dermatology and Venereology. 2015 Dec;29(12):2295-305. 
  18. Sassalos TM, Fields TS, Levine R, Gao H. Retinal neovascularization from a patient with cutis marmorata telangiectatica congenita. Retinal Cases and Brief Reports. 2021 Jan 1;15(1):77-80. 
  19. Thomas FP, Guergueltcheva V, Gondim FA, Tournev I, Rao CV, Ishpekova B, Kinsella LJ, Pan Y, Geller TJ, Litvinenko I, De Jonghe P. Clinical, neurophysiological and morphological study of dominant intermediate Charcot-Marie-Tooth type C neuropathy. Journal of neurology. 2016 Mar 1;263(3):467-76.
  20. Kumar A, Zastrow DB, Kravets EJ, Beleford D, Ruzhnikov MR, Grove ME, Dries AM, Kohler JN, Waggott DM, Yang Y, Huang Y. Extracutaneous manifestations in phacomatosis cesioflammea and cesiomarmorata: case series and literature review. American Journal of Medical Genetics Part A. 2019 Jun;179(6):966-77.
  21. Dereure O. Cutis marmorata telangiectatica congenita: mutations in a susceptibility gene involved in cerebrovascular accidents. InAnnales de dermatologie et de venereologie 2016 Jan (Vol. 143, No. 1, pp. 96-97).
  22. Abumansour IS, Hijazi H, Alazmi A, Alzahrani F, Bashiri FA, Hassan H, Alhaddab M, Alkuraya FS. ARL6IP6, a susceptibility locus for ischemic stroke, is mutated in a patient with syndromic Cutis Marmorata Telangiectatica Congenita. Human genetics. 2015 Aug;134(8):815-22.
  23. Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. Journal of the American Academy of Dermatology. 1987 Apr 1;16(4):899-906. 
  24. Bui TN, Corap A, Bygum A. Cutis marmorata telangiectatica congenita: a literature review. Orphanet journal of rare diseases. 2019 Dec;14(1):1-8. 
  25. Devillers AC, Oranje AP. Cutis marmorata telangiectatica congenita: clinical features in 35 cases. Archives of dermatology. 1999 Jan 1;135(1):34-8. 
  26. Gerritsen MJ, Steijlen PM, Brunner HG, Rieu PN. Cutis marmorata telangiectatica congenita: report of 18 cases. British Journal of Dermatology. 2000 Feb;142(2):366-9. 
  27. South DA, Jacobs AH. Cutis marmorata telangiectatica congenita (congenital generalized phlebectasia). The Journal of pediatrics. 1978 Dec 1;93(6):944-9.
  28. Picascia DD, Esterly NB. Cutis marmorata telangiectatica congenita: report of 22 cases. Journal of the American Academy of Dermatology. 1989 Jun 1;20(6):1098-104. 
  29. Nasser Rashid D, Tariq G, Zaheer Iqbal A. Cutis marmorata telangiectatica congenita.
  30. Mirzaa GM, Conway RL, Gripp KW, Lerman‐Sagie T, Siegel DH, deVries LS, Lev D, Kramer N, Hopkins E, Graham Jr JM, Dobyns WB. Megalencephaly‐capillary malformation (MCAP) and megalencephaly‐polydactyly‐polymicrogyria‐hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis. American Journal of Medical Genetics Part A. 2012 Feb;158(2):269-91.
  31. Del Boz J, Serrano MD, Gómez E, Vera Á. Neonatal lupus erythematosus and cutis marmorata telangiectatica congenita‐like lesions. International journal of dermatology. 2009 Nov;48(11):1206-8.
  32. South DA, Jacobs AH. Cutis marmorata telangiectatica congenita (congenital generalized phlebectasia). The Journal of pediatrics. 1978 Dec 1;93(6):944-9.
  33. Mazereeuw‐Hautier J, Carel‐Caneppele S, Bonafé JL. Cutis marmorata telangiectatica congenita: report of two persistent cases. Pediatric dermatology. 2002 Nov;19(6):506-9. 
  34. Hinek A, Jain S, Taylor G, Nykanen D, Chitayat D. High copper levels and increased elastolysis in a patient with cutis marmorata teleangiectasia congenita. American Journal of Medical Genetics Part A. 2008 Oct 1;146(19):2520-7. 
  35. Torrelo A, Zambrano A, Happle R. Cutis marmorata telangiectatica congenita and extensive mongolian spots: type 5 phacomatosis pigmentovascularis. British Journal of Dermatology. 2003 Feb;148(2):342-5. 
  36. Andreev VC, Pramatarov K. Cutis marmorata telangiectatica congenita in two sisters. British Journal of Dermatology. 1979 Sep;101(3):345-50. 
  37. Deshpande AJ. Cutis mormorata telangiectatica congenital successfully treated with intense pulsed light therapy: a case report. Journal of Cosmetic and Laser Therapy. 2018 Apr 3;20(3):145-7. 
  38. Sekido M, Sasaki K, Togashi S, Adachi K. Laser therapy treatment of phacomatosis pigmentovascularis type II: two case reports. 
  39. Livingston EH, Lee S. Percentage of burned body surface area determination in obese and nonobese patients. Journal of surgical research. 2000 Jun 15;91(2):106-10. 
  40. Hu IJ, Chen MT, Tai HC, Tsao PN, Chou HC, Hsieh WS. Cutis marmorata telangiectatica congenita with gangrenous ulceration and hypovolaemic shock. European journal of pediatrics. 2005 Jul 1;164(7):411-3. 

 

 

 

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