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22 Vascular Malformations

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22.11 Syndromic Forms

In syndromic forms, vascular malformations are associated with general disorders. The forms that involve the hand and upper limb are Maffucci syndrome, Klippel-Trenaunay syndrome, ParkWeber syndrome, Proteus syndrome and Cloves syndrome.

22.11.1 Maucci Syndrome (MS)

Maffucci syndrome is a rare congenital disorder characterized by multiple central cartilaginous tumours (enchondromas) in association with cutaneous spindle cell haemangiomas. Patients with MS have a high incidence of malignant transformation [37]. MS was rst described in 1881 as differential diagnosis with Ollier’s syndrome, which is a simple multiple enchondromatosis. Treatment of MS is surgical excision of enchondromas and vascular malformations.

22.11.2 Klippel-Trenaunay Syndrome (KTS)

22.11.3 Park-Weber Syndrome (PKWS)

PKWS is often confused with KTS.Clinical features are capillary venous malformations that involve upper or lower limb, arteriovenous shunts and anomalies and hypertrophy of bones and tissues.

22.11.4 Proteus Syndrome (PS)

Proteus syndrome is a mosaic, progressive overgrowth disorder involving vessels, skin and skeleton and caused by a somatic activating mutation in AKT1 [38, 39].

Proteus syndrome appears with localized macrosomia, congenital lipomatosis and slow ow vascular malformations, connective tissue nevus and epidermal nevus. There are usually some manifestations at birth. The vascular abnormalities that have been reported in Proteus syndrome are capillary and slow-ow venous malformation [38–40].

Patients with Proteus syndrome have a high mortality incidence at 22 years of age [41].

Clinical features are (1) port-wine stains that may be localized to a relatively small area or involve the lateral aspect of one or more extremities; (2) limb hypertrophy or gigantism, presenting with an extremity that is longer and larger in circumference than the unaffected limb; (3) large clusters of varicose veins extending throughout the entire extremity; and (4) large lateral venous collector called the vena marginalis lateralis [15]. Most of these patients can be treated by compression and sclerotherapy and by sleeping in Trendelenburg position. However, some patients have pain, venous ulceration, venous thrombosis and pulmonary embolism that do not respond to conservative measures and need to be treated aggressively. It is important to stop bleeding that may sometimes be copious [27].

22.11.5 CLOVES Syndrome

The acronym CLOVES stands for congenital lipomatous overgrowth (CLO), vascular malformation (V), epidermal nevi (E) and scoliosis and spinal deformities (S) [42].

22.11.6 Characteristics ofCLOVES

(Fig.22.8)

1. Various size lipomatous mass of the torso

2. Vascular malformations

3. Musculoskeletal deformities especially of

hands and feet

4. Scoliosis and anomalies of the spine and chest

5. Neurologic involvement

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Fig. 22.8 CLOVES syndrome in a 9-year-old male

Unlike Proteus syndrome, CLOVES does not present with connective tissue nevi and consists of a lipomatous mass with an aggressive overgrowth and high rate of recurrence [42, 43].

This overgrowth leads to exhaustion due to the heavy weight of the overgrowing limb. When symptomatic treatment fails, surgical excision of the mass or amputation should be considered.

References

1. Lee BB, etal. Phlebology. 2007;22(6):283–6.

2. Marzella L. Indicazioni diagnostico terapeutiche per le Malformazioni vascolari dell’Arto superiore:valutazione dell’appropriatezza tra un gruppo di esperti e adozione di linee guida multidisciplinari. Chirurgia della Mano. 2016;53(3):77–87.

3. Belov S, Loose DA, Weber J.Vascular malformations. Reinbek: Einhorn Presse; 1989. p.29.

4. Szilagyi DE, Smith RF, Elliott JP, et al. Congenital arteriovenous anomalies of the limbs. Arch Surg. 1976;111:423–9.

5. Gomes AS, Busuttil RW, etal. Congenital arteriovenous malformations. The role of transcatheter arterial embolization. Arch Surg. 1983;118:817–25.

6. Gomes MMR, Bernatz PE.Arteriovenous stulas: a review and ten-year experience at the Mayo Clinic. Mayo Clin Proc. 1970;45:81–102.

7. Malan E, Pugliorisi A. Congenital angio-dysplasias of the extremities. I. Generalities and classication; venous dysplasias. J Cardiovasc Surg (Torino). 1964;5:87–130.

8. Malan E, Pugliorisi A. Congenital angiodysplasias of the extremities. II. Arterial, arterial and venous, and haemolymphatic dysplasias. J Cardiovasc Surg. 1965;6:255–345.

L. Marzella and P. di Giuseppe

9. Wolfe SW, Pederson WC, Kozin SH, Cohen MS. Green’s operative hand surgery, 2-volume. 6th ed. Philadelphia: Elsevier; 2011. p.2236–9.

10. Angiome VR.Die Krankhaften Gerschwulste. Berlin: Hirschwald; 1863.

11. Mulliken J, Glowacky J.Hemangiomas and vascular malformations in infants and children: a classication based on endothelial characteristics. Plast Reconstr Surg. 1982;69:412–22.

12. Mattassi R. Hemangiomas and vascular malformation. Milan: Springer; 2009.

13. Konez O.Imaging in vascular anomalies. Medscape, October 2015

14. Cabbade EB.Xerography as an aid in planning resection of vascular malformation of the upper extremities. J Hand Surg Am. 1985;10:670–4.

15. Lee BB, Villavicencio L. Congenital vascular malformations: general considerations. In: Rutherford vascular surgery, vol. 68. Amsterdam: Elsevier; 2014.

16. Kennedy WP.Epidemiologic aspects of the problem of congenital malformations. In: Persaud TNV, editor. Problems of birth defects. Baltimore, MD: University Park Press; 1977. p.35–52.

17. Stevenson AC, Johnston HA, Stewart MIP, Golding DR.Congenital malformations. A report of a study of series of consecutive births in 24 centres. Bull WHO. 1966;34(Suppl):9 and 100–102 (Extracts).

18. Myrianthopoulos NC, Chung CS. Congenital malformations in singletons. Epidemiologic survey. In: Bergsma D, editor. Birth defects original article series, vol. X, no II (Miami Symposia Specialists for the National Foundation-March of Dimes); 1974.

19. Kulungowski AM, Mulliken JB.Expression of androgen, estrogen, progesterone and growth hormone receptors in vascular malformations. Plast Reconstr Surg. 2012;129(6):919–24.

20. Luks VL, Kamitaki N, et al. Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA. J Pediatr. 2015;166(4):1048–54.e1–5.

21. Ayturk UM, Couto JA.Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma. Am J Hum Genet. 2016;98(4):789–95.

22. Couto JA, Huang L.Endothelial cells from capillary malformations are enriched for somatic GNAQ mutations. Plast Reconstr Surg. 2016;137(1):77e–82e.

23. Couto JA, Huang L.Somatic MAP2K1 mutations are associated with extracranial arteriovenous malformation. Am J Hum Genet. 2017;100(3):546–54.

24. Belov S. Surgical treatment of congenital vascular defects. In: Chang JB, editor. Modern vascular surgery. NewYork: Springer; 1994. p.383–97.

25. Hassanein HC, Mulliken JB.Evaluation of terminology for vascular anomalies in current literature. Plast Reconstr Surg. 2011;127(1):347–51.

26. Blei F.Basic science and clinical aspects of vascular anomalies. Curr Opin Pediatr. 2005;17(4):501–9.

27. Ek ET, Suh N.Vascular anomalies of hand and wrist. J Am Acad Orthop Surg. 2014;22:352–60.

22 Vascular Malformations

https://t.me/medicina_free

267

28. Jacobs BJ, Anzarut A, Guerra S, Gordillo G, Imbriglia JE.Vascular anomalies of the upper extremity. J Hand Surg Am. 2010;35(10):1703–9.

29. Pearce WH, Rutherford RB, Whitehill TA, Davis K. Nuclear magnetic resonance imaging in patients with congenital vascular malformations of the limbs. J Vasc Surg. 1988;8:64–70.

30. Lee BB, Choe YH, Ahn JM, etal. The new role of MRI (magnetic resonance imaging) in the contemporary diagnosis of venous malformation: can it replace angiography? J Am Coll Surg. 2004;198: 549–58.

31. Coursley G, Ivins JC, Barker NW. Congenital arteriovenous stulas in extremities. Angiology. 1956;7:201–17.

32. Park UJ, Do YS, Park KB, Park HS, Kim YW, Lee BB, Kim DL.Ann Vasc Surg. 2012;26(5):643–8.

33. Ahmad Khan RD.Glomus tumours: outcome based on tumour location in the hand. J Pak Med Assoc Nov. 2015;65(11 Suppl 3):S3–7.

34. Hill RA, Pho RW, Kumar VP. Resection of vascular malformations. J Hand Surg Br. 1993;18(1):17–21.

35. Upton J, Coombs CJ, Mulliken JB, Burrows PE, Pap S.Vascular malformations of the upper limb: a review of 270 patients. J Hand Surg Am. 1999;24(5):1019–35.

36. Di Giuseppe P.Surgical treatment of vascular malformation in the hand. In: Hemangiomas and vascular malformation. Milan: Springer; 2009. p.287–92.

37. Amyere M, Dompmartin A.Common somatic alterations identied in Maffucci syndrome by molecular karyotyping. Mol Syndromol. 2014;5(6):259–67.

38. Kepler-Noreuil KM, et al. Am J Med Genet A. 2017;173(9):2359–65.

39. Ou M etal. Mol Clin Oncol. 2017;6(3):381–3.

40. Asillian A, etal. Adv Biomed Res. 2017;7:6–27.

41. Sapp JC, et al. Genet Med. 2017. https://doi.

org/10.1038/gim.2017.65.

42. Bloom J, Upton J III.Cloves syndrome. J Hand Surg Am. 2013;38(12):2508–12.

43. Alomari AI.Characterization of a distinct syndrome that associates complex truncal overgrowth, vascular, and acral anomalies: a descriptive study of 18 cases of CLOVES syndrome. Clin Dysmorphol. 2009;18(1):1–7.

Macrodactilies

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ScottN.Oishi, MarybethEzaki, TerriBeckwith, andArenaSayavong

Abstract

Macrodactyly is the descriptive name for ngers or toes that are enlarged most often due to pathway mutations regulating growth, protein synthesis, and cellular proliferation. The enlargement in these patients is extremely variable and can affect the nger(s) only or the entire limb. These patients typically present for evaluation early in life as the enlarged digits/extremities are usually recognized at birth. It is critical to identify those children in which macrodactyly is extensive or progressive, as surgical and/or pharmacologic intervention may be warranted. Parental education and counseling about realistic expectations are imperative too.

Keywords

Macrodactyly · Overgrowth · PI3K-AKT · Fibroadipose hand · PROS

23.1 Introduction

As the name suggests, macrodactyly means abnormal enlargement of one or more digits of the hand or foot. Although associated with neurobromatosis and Klippel-Trenaunay and Ollier syndromes, the most common etiology of this condition was only recently discovered using newly developed advanced sequencing techniques. A mutation in the PIK3CA (phosphatidylinositol-4,5-biphosphate 3-kinase) pathway was identied in affected tissues [1, 2]. This somatic mosaic gain-of-function mutation leads to dysregulation of growth through the mTOR pathway (Fig.23.1) [2].

This pathway is involved with the regulation of growth, protein synthesis, and cellular proliferation and is also implicated in various adult malignancies. Other overgrowth conditions have been shown to be caused by mutations in this mTOR pathway, the so-called PIK3CA- related overgrowth spectrum (PROS) (Fig.23.2).

The mutation occurs in the postzygotic embryonic period, thereby occurring in some cells and not in others. As a result, DNA sequencing of unaffected tissue will fail to show this upregulation in PIK3CA.Sanger sequencing is much less

S. N. Oishi (*) · M. Ezaki · T. Beckwith · A. Sayavong Charles E.Seay, Jr. Hand Center, Texas Scottish Rite Hospital for Children, Center for Excellence in Hand, Upper Extremity and Microvascular Surgery, Dallas, TX, USA e-mail: Scott.Oishi@tsrh.org;

Terri.Beckwith@tsrh.org; Arena.Sayavong@tsrh.org

269

270

PI3K-AKT Signaling Pathway

• Macrodactyly

• Hemih Multiple Lipomatosis (HHML)

• Fibroadipose

• Muscle Hemih

• F

• CLO

• Megalencephaly Capillar

• Skin disorders: Epider Seborrheic Benign lichenoid

Cell cycle/apoptosis regulation, metabolism, angiogenesis

)

Phenotypic Spectrum of PROS

Tissue-Specific

Phenotypic Severity

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S. N. Oishi et al.

RTK

PIK3CA-Related Overgrowth Spectrum (PROS)

yperplasia

overgrowth (FAO)

ypertrophy

acial Infilitrating Lipomatosis

VES

y Malformation (MCAP)

mal nevi,

keratoses,

keratoses

PI3K

PIP3

Bannayan - Riley - Ruvalcaba and Cowden and Type II Segmental Cowden syndrome Lhermitte–Duclos disease

PIP3

P P

PTEN

Fig. 23.1 Signaling pathway of PI3CA expression [2]

Fig. 23.2 Phenotypic

variating related to the spectrum of PROS [2]

Distribution

Pleiotropic

PDK1

• Proteus Syndrome (AKT1)

Thr308

AKT

Ser473

mTOR2 mTOR1

mTOR

• Lipodystrophy syndrome - Hypoglycemia (AKT2)

• Hemimegalencephaly and Megalencephaly-polymicrosyria polydactyly-hydrocephalus (MPPH) (AKT3

• Hemimegalencephaly

Muscular

Macrodactyly

SK,

BLK

ILM

FAO/HHML

CLOVES

TSC2TSC1

Facial

Infiltrating

Lipomatosis

DMEG/

HMEG

MCAP

expensive than high-throughput but is slower and less sensitive and can have some false negatives because it has difculty in distinguishing lowlevel mutations in the tissue. Next-generation sequencing (NGS) uses a technique of massively parallel sequencing and can pick up relatively low levels of mutation in the tissue. The burden of mutation in a cell population or the tissue is thought to be related to phenotype.

23.2 Clinical Presentation

The digits usually affected are in the median distribution of the hand, with the index nger being the most common (Fig.23.3).

Occasionally, however, it can be isolated to the ulnar distribution of the hand (Fig.23.4).

Macrodactyly was thought to be inuenced by the associated nerve, which is grossly enlarged as

23 Macrodactilies

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Fig. 23.3 (a, b) Macrodactyly involving the thumb and index ngers. Note the thumb hyperextension which is due to disproportionate palmar overgrowth

271

well. All soft and bony tissues of the digit are involved. The osseous structures enlarge and joints become stiff and hyperostotic. This enlargement needs not be limited to the digit, as proximal involvement of the hand and median nerve in the carpal tunnel is often seen. Nerve histology has been termed a lipobromatous hamartoma, descriptive of fatty and brous enlargement, surrounding dispersed but otherwise functioning nerve fascicles. Enlargement of the nerve in the carpal canal may cause a compressive neuropathy (Fig.23.5).

Fig. 23.4 Minimal enlargement of the ring nger with a normal thumb and index nger, defying the “nerve territory” concept

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Fig. 23.5 Nerve histology in hematoxylin and eosin stain. (a) Normal nerve. (b) Macrodactyly nerve

23.3 Evaluation

Because of the disparity in digit/limb size, these patients are often seen at an early age [3, 4]. A thorough examination is mandatory to assess overall limb size as well as other ndings possibly associated with PROS. It is especially important to identify those patients who have the

macrodactyly associated with overall limb enlargement (macrodystrophic lipomatosis) (Fig.23.6) as rapid growth may occur in the digits/limb and earlier surgical and/or medical intervention may be required. Macrodactyly can also be part of lymphatic overgrowth, so evaluation for vascular anomalies is also warranted. The macrodactylus digits are usually, and will be, stiff

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Fig. 23.6 Macrodystrophic lipomatosis. Note the entire limb enlargement with normal appearing ring and little ngers

and lacking full exion. All physical ndings should be pointed out to the parents to help inform their long-term expectations for the limb.

In patients who have growth proportionate to overall growth of the child, observation is warranted until the digits become the size of the parent of the same sex. Some digits may never need surgical intervention to slow growth (Fig.23.7).

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Fig. 23.7 Macrodactyly of the little nger that likely will never need surgical intervention to slow growth

Rapidly enlarging digits may develop angulation due to asymmetric growth plate involvement. In these instances, epiphysiodesis, corrective osteotomy, and debulking procedures are warranted (Fig.23.8). A good algorithm for this strategy is outlined in a paper by Gluck and Ezaki (Fig.23.9).

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Fig. 23.8 Middle nger with angular deformity. (a, b) Before and after epiphysiodeses and shaft osteotomy. K-wires are used to maintain alignment until healing is

complete. (c, d) The illustration portrays the cuts made at each level. “x” marks sites of planned epiphysiodeses [5]

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23.4 Treatment

Treatment must be individualized to each patient. In patients who have rapidly enlarging digits or the macrodystrophic lipomatosis variety, referral to a hematologist may be warranted for possible institution of an mTOR blocker such as rapamycin [6]. Because of possible associated side effects and unknown long-term sequelae, routine use of rapamycin in all macrodactyly patients is not recommended.

Wound healing and scar formation are also affected by the mutated genetic pathway, and parents should be informed of possible problems

before surgery. Meticulous wound care is especially important in these patients.

In most cases, surgery is undertaken when the child’s digit reaches the size of the same sex parents. Surgery usually entails soft tissue debulking, physeal arrest, and osteotomy if signicant angulation is present (Figs. 23.10 and 23.11). Digital vessels are typically thin, atretic, and often not well seen. Only one side of the nger should be debulked in this manner because of the risk of devascularizing the digit. A technical tip demonstrated in Fig. 23.10 is the placement of marker “darts” at the interphalangeal joint levels. This detail will help in aligning aps during

Fig. 23.9 Algorithm for intervention of macrodactyly [5]

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