Cutis verticis gyrata

INTRODUCTION — Cutis verticis gyrata is a rare, congenital or acquired scalp condition characterized by convoluted folds and deep furrows that resemble the surface of the cerebral cortex (picture 1) [1-3]. It may occur as a benign, primary condition [4], in association with neuropsychiatric or ophthalmologic abnormalities, or may be secondary to a number of localized or systemic, inflammatory or neoplastic diseases [5]. Cutis verticis gyrata has also been reported in association with several genetic syndromes, including Turner syndrome, Noonan syndrome, and craniosynostosis syndromes.

This topic will discuss the clinical presentation, diagnosis, and treatment of primary and secondary cutis verticis gyrata. Other scalp disorders are discussed separately. (See "Approach to the patient with a scalp disorder".)

CLASSIFICATION — Cutis verticis gyrata is classified as primary, essential or nonessential, or secondary [3,6].

●Primary essential cutis verticis gyrata occurs in isolation in otherwise normal individuals.

●The primary nonessential form is associated with neuropsychiatric or ophthalmologic abnormalities. This form is called cutis verticis gyrata-intellectual disability.

●Secondary cutis verticis gyrata results from neoplastic or inflammatory scalp conditions, systemic diseases, or genetic disorders [3].

EPIDEMIOLOGY — Primary cutis verticis gyrata is a rare disorder, with an estimated prevalence of 1 in 100,000 in males and 0.026 in 100,000 in females [7]. The reason for the observed male predominance is unknown [8]. A higher prevalence, ranging from 0.2 to 4.5 percent, has been reported in patients with intellectual disability [7,9,10].

Secondary forms of cutis verticis gyrata are slightly more common than the primary forms [3]. They can occur at any age, without sex predilection.

PATHOGENESIS — The etiology of primary cutis verticis gyrata is unknown. Because of the typical onset after puberty and male preponderance, endocrine factors are thought to play a role in primary forms. In one study of 15 psychiatric patients with primary cutis verticis gyrata, the plasma levels of free testosterone were significantly lower than in normal controls, whereas no difference was found in the levels of cortisol or thyroid, sex, or growth hormones [11].

Chromosomal abnormalities, including the fragile X syndrome and other chromosomal fragile sites, have been reported in some patients with primary cutis verticis gyrata and intellectual disability [12-14]. Cutis verticis gyrata may also be associated with sex chromosome abnormalities (eg, Turner syndrome, Klinefelter syndrome).

A multiplicity of cutaneous and systemic conditions may be the underlying cause of secondary cutis verticis gyrata, including inflammatory scalp dermatoses, benign cutaneous tumors and hamartomas, endocrine diseases, internal cancers, and genetic syndromes. Congenital lymphedema is thought to be involved in the pathogenesis of cutis verticis gyrata in Turner syndrome and Noonan syndrome. (See 'Associated conditions' below.)

When associated with acromegaly, elevated growth hormone levels and insulin-like growth factor 1 (IGF-1) affect skin and soft tissue, leading to glycosaminoglycan accumulation and overproduction of connective tissue [15].

PATHOLOGY — In primary cutis verticis gyrata, histologic examination of a scalp biopsy shows a normal epidermis with increased number and size of collagen bundles and increased matrix in the dermis [16]. In primary cutis verticis gyrata associated with pachydermoperiostosis (primary hypertrophic osteoarthropathy), histologic changes include enlargement of epidermal appendages and increased fibroblasts, collagen, and ground substance [17,18]. In secondary forms, histology may reflect the underlying disorder [16].

CLINICAL FEATURES — Cutis verticis gyrata presents as an asymptomatic thickening of the scalp with formation of folds and furrows resembling the cerebral cortex. Involvement of the face has also been reported [19-21].

Primary cutis verticis gyrata — Primary cutis verticis gyrata typically appears after puberty, with 90 percent of cases occurring before the age of 30 years, and is more common in males than in females [6]. It is exceedingly rare in infants and young children. When present at birth, cutis verticis gyrata should raise suspicion of a cerebriform intradermal nevus or of an associated genetic syndrome. (See 'Associated conditions' below.)

In primary cutis verticis gyrata, the scalp folds are symmetric, run anteroposteriorly, and typically involve the vertex and occiput (picture 1). Occasionally, the entire scalp can be affected. The fold number ranges from 2 to 30, with a width of 0.5 to 2 cm, and a furrow depth of approximately 1 cm [22]. Typically, the scalp folds cannot be flattened by pressure or traction.

Primary cutis verticis gyrata occurring in isolation (primary essential cutis verticis gyrata) is rare. More often, it is seen in individuals with neuropsychiatric or ophthalmologic abnormalities, including intellectual disability, cerebral palsy, epilepsy, seizures, cataract, strabismus, and retinitis pigmentosa (primary nonessential cutis verticis gyrata) (picture 2) [8,23]. (See 'Classification' above.)

Primary cutis verticis gyrata may be a manifestation of pachydermoperiostosis (primary hypertrophic osteoarthropathy, MIM #167100), a rare autosomal dominant disease with variable expression characterized by subperiosteal bone formation at the distal ends of the long bones, hypertrophy of the soft tissues of the face and scalp resulting in coarsening of facial features, clubbing of the digits, seborrheic hyperplasia, hyperhidrosis, and cutis verticis gyrata [24].

Secondary cutis verticis gyrata — Secondary cutis verticis gyrata may occur at any age and is equally frequent in males and females. The clinical appearance varies with the underlying cause. Usually, the scalp folds and furrows show a disordered pattern and are asymmetrically distributed over the scalp (picture 3).

Inflammatory and systemic disorders lead to mild corrugation of the entire scalp. Cutis verticis gyrata due to neoplasms of the scalp usually presents as a localized furrowing of the scalp that can gradually enlarge to involve the entire scalp.

Associated conditions — Numerous cutaneous and systemic conditions may be associated with secondary cutis verticis gyrata, including [3]:

●Benign scalp tumors and hamartomas, including cerebriform intradermal nevus [25,26], neurofibromas, fibroma, cylindroma, collagenoma, nevus lipomatosus, and connective tissue nevi [5,26-29].

●Inflammatory dermatoses, including eczema, psoriasis, acne, and pemphigus [5,30].

●Internal malignancies [31-34].

●Endocrine diseases, including acromegaly [35-39], myxedema, Graves' disease [40], acanthosis nigricans, and insulin resistance syndrome [41,42].

●Amyloidosis [43].

●Hyperimmunoglobulin E syndrome [19,44].

●Treatment with vemurafenib and whole-brain radiotherapy [45,46].

●Human immunodeficiency virus (HIV)-related lipodystrophy [47].

●Genetic syndromes, including Turner syndrome [16,48,49], Klinefelter syndrome [50,51], Noonan syndrome [52], Darier disease [53,54], cutaneous leiomyomatosis [55], craniosynostosis syndromes (Apert syndrome, Beare-Stevenson syndrome) [56], pachydermoperiostosis [15,57], and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome [58]. (See "Darier disease" and "Hereditary leiomyomatosis and renal cell cancer (HLRCC)" and "Craniosynostosis syndromes" and "SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome".)

•The association between cutis verticis gyrata and Turner syndrome is well recognized [48,49,59]. Turner syndrome is an X-linked condition only affecting females characterized by short stature, primary amenorrhea, and other dysmorphic features (eg, "shield" chest with widely spaced nipples, webbed neck, cubitus valgus, short fourth metacarpal) [16,48,49]. Intrauterine lymphedema due to agenesia or hypoplasia of lymphatic vessels is thought to be the cause of cutis verticis gyrata in infants with Turner syndrome [48]. (See "Clinical manifestations and diagnosis of Turner syndrome".)

•Cutis verticis gyrata has been reported in patients with Noonan syndrome (MIM #163950), a relatively common autosomal dominant disorder characterized by minor facial dysmorphism (hypertelorism, downward eye slant, and low-set ears), proportionate short stature, and heart disease (picture 4) [5,60,61]. Congenital lymphoedema is common in Noonan syndrome and has been postulated as the underlying cause of cutis verticis gyrata in these patients [48,49,62,63]. (See "Noonan syndrome".)

•Cohen syndrome (MIM #216550) is a rare autosomic recessive disorder caused by mutation in the chromosome 8q22.2 and characterized by severe psychomotor delay, microcephaly, characteristic facial features, progressive retinochoroidal dystrophy, myopia, and intermittent isolated neutropenia [64]. A variant of Cohen syndrome with microcephaly, cutis verticis gyrata of the scalp, retinitis pigmentosa, cataracts, sensorineural hearing loss, kyphoscoliosis, and intellectual disability has been described in two nonconsanguineous brothers [65,66].

DIAGNOSTIC APPROACH — The diagnostic approach to patients with cutis verticis gyrata varies, depending upon the findings from physical examination and history.

●The finding of cutis verticis gyrata in a fetus on prenatal ultrasound imaging should raise suspicion of Turner syndrome or Noonan syndrome [67]. In newborns, the finding of cutis verticis gyrata should prompt clinical, laboratory, and imaging evaluation for other morphologic abnormalities associated with Turner syndrome or Noonan syndrome. (See "Clinical manifestations and diagnosis of Turner syndrome" and "Noonan syndrome".)

A skin biopsy may be necessary if the lesion is suspected to be a cerebriform intradermal nevus.

●In adolescents and young adults, the finding of folds and furrows symmetrically distributed on the scalp and oriented anteroposteriorly in the absence of systemic symptoms suggests the diagnosis of primary essential cutis verticis gyrata (picture 1). Radiologic imaging (eg, contrast-enhanced computed tomography [CT] scan) can confirm that the lesion is restricted to the skin and does not involve underlying structures [68]. A history of intellectual disability or neurologic or ocular abnormalities suggests the diagnosis of nonessential cutis verticis gyrata. A scalp biopsy is usually not necessary to confirm the diagnosis in these patients.

●Early onset, irregular or unusual patterns of folds and furrows, and presence of systemic symptoms raise suspicion of a secondary form of cutis verticis gyrata. A scalp biopsy and appropriate laboratory and imaging studies based upon the patient's history and clinical findings are required for the precise diagnosis of the underlying condition. (See 'Associated conditions' above.)

●CT scan can help determine the presence of a pituitary adenoma [36]. Due to the potential association of pituitary adenoma with cutis verticis gyrata in the absence of any other features of acromegaly, some authors recommend endocrine assessment of the growth hormone/insulin-like growth factor 1 (IGF-1) axis (eg, serum IGF-1, growth hormone, and nonsuppressed growth hormone) after glucose load [15].

TREATMENT — The treatment of cutis verticis gyrata depends upon the etiology, extent of scalp involvement, and patient preference. Primary cutis verticis gyrata is a benign condition and treatment may be limited to good scalp hygiene to avoid accumulation of secretions in the furrows [8].

However, patients with extensive or disfiguring lesions may require scalp reduction procedures for cosmetic reasons. Small, localized lesions can be excised and closed primarily. Larger lesions can be removed with several approaches, including serial excisions or use of tissue expansion techniques [69-71].

Skin scalp subcision under local anesthesia has also been reported with satisfactory results [72]. There is one report of the use of filler injections into scalp furrows in a single patient with cutis verticis gyrata and HIV-related lipodystrophy, with reduction of the furrow depth at 10 months [47].

A case report notes that autologous fat transfer markedly improved the appearance of primary essential cutis verticis gyrata [73]. The follow-up was limited to 24 weeks. This approach requires a larger group of patients studied over a longer period of time, assessing results from one or more treatments with autologous fat transfer.

In patients with secondary cutis verticis gyrata, treatment is primarily directed at the underlying condition. A close follow-up over time is advised for patients with cerebriform intradermal nevus, because of the potential for malignant transformation of congenital melanocytic nevi. When possible, surgical resection may be considered [74]. (See "Congenital melanocytic nevi", section on 'Management'.)

One case report notes that cutis verticis gyrata secondary to acromegaly spontaneously improved following surgical treatment of the underlying pituitary adenoma [75]. The authors stress the importance of early diagnosis and treatment of the underlying etiology of nonessential cutis verticis gyrata.

SUMMARY AND RECOMMENDATIONS

●Definition and classification – Cutis verticis gyrata is a rare, congenital or acquired scalp condition characterized by convoluted folds and deep furrows that resemble the surface of the cerebral cortex. Cutis verticis gyrata may occur as a primary condition, often in association with neuropsychiatric or ophthalmologic abnormalities, or may be secondary to a number of localized or systemic inflammatory or neoplastic diseases. (See 'Introduction' above and 'Classification' above.)

●Clinical presentation – In primary cutis verticis gyrata, the folds are symmetric, run anteroposteriorly, and typically involve the vertex and occiput (picture 1). In contrast, in secondary forms, folds and furrows are irregular and asymmetrically distributed over the scalp (picture 3). (See 'Clinical features' above.)

●Associated conditions – Neuropsychiatric or ophthalmologic abnormalities, including intellectual disability, cerebral palsy, epilepsy, cataract, and retinitis pigmentosa are frequently associated with primary cutis verticis gyrata. Cutaneous and systemic conditions associated with secondary cutis verticis gyrata include inflammatory scalp dermatoses, cutaneous tumors and hamartomas, endocrine diseases, internal cancers, and genetic syndromes. (See 'Associated conditions' above.)

●Diagnosis – The diagnostic approach to patients with cutis verticis gyrata varies, depending upon the findings from physical examination and history.

•In adolescents and young adults, the finding of folds and furrows oriented anteroposteriorly in the absence of systemic symptoms suggests the diagnosis of primary essential cutis verticis gyrata. A history of intellectual disability or neurologic or ocular abnormalities suggests the diagnosis of nonessential cutis verticis gyrata. (See 'Primary cutis verticis gyrata' above.)

•Early onset, irregular or unusual patterns of folds and furrows, and presence of systemic symptoms suggests secondary cutis verticis gyrata. In newborns, the finding of cutis verticis gyrata should prompt clinical, laboratory, and imaging evaluation for other morphologic abnormalities associated with Turner syndrome or Noonan syndrome. (See 'Secondary cutis verticis gyrata' above and 'Associated conditions' above.)

●Treatment – Primary cutis verticis gyrata is a benign condition and treatment is not needed. However, patients with extensive or disfiguring lesions may require scalp reduction procedures or use of cutaneous fillers for cosmetic reasons. Treatment of secondary cutis verticis gyrata is directed at the underlying condition. (See 'Treatment' above.)