Type 4 Woolly Hair-Palmoplantar Keratoderma Syndrome: A Rare Entity

Dear Editor,

A 35-year-old man born out of non-consanguineous marriage presented to the dermatology OPD with abnormal hair texture since birth and thickening over the palms and soles since 6 months of age. There was no history of similar skin and hair changes among siblings or other family members. No history of delayed milestones and mental retardation was elicited. There was no history of syncopal attacks, palpitations in the patient, or sudden deaths among family members. On examination, his scalp hair was sparse, short, and extremely curly and could be pulled out easily. Trichoscopy and trichogram of the pulled hairs revealed difference in the hair shaft diameter [Figure 1]. Eyebrow hairs were similarly affected. There was diffuse well-defined palmoplantar keratoderma (PPK) with transgradiens. Severe contractures were noted at the interphalangeal joints. Nail plate thickening with subungual debris was also seen [Figure 2]. Teeth abnormality, foul-smelling plaques, and involvement of tendoachilles were not present. Other associations of woolly hair such as keratosis pilaris, webbed neck, facial dysmorphism, skin fragility, koilonychia, and hypoplastic nails and teeth were not present. No evidence of progressive neurologic degeneration, short stature, deafness, and hypogonadism was noted.

Figure 1.

(a-b) Woolly hair. (c) Trichoscopy shows difference in diameter of the hair shaft. (d) Trichogram shows multiple hair shafts of varying diameter

Figure 2.

(a): Diffuse palmoplantar keratoderma with transgradiens and severe contractures. (b): Dorsal surface of both hands showing transgradiens. (c): Sparse eye brows with woolly hair. No teeth abnormality

Biopsy from the left palm revealed epidermal hyperplasia with hyperkeratosis, parakeratosis, and hypergranulosis. No evidence of epidermolytic hyperkeratosis. Superficial dermis showed lymphocytic inflammatory infiltrate with few dilated blood vessels [Figure 3]. Chest X-ray revealed no cardiomegaly. A cardiac consultation was advised, ECG and 2-D echocardiography revealed no cardiac rhythm abnormalities and cardiomyopathy respectively. Genetic workup for KANK2 mutation was advised but couldn't be done due to financial constraints.

Figure 3.

Histopathology of palms showing massive hyperkeratosis, parakeratosis and hypergranulosis. [H and E,10X]

Given the presence of woolly hair and diffuse palmoplantar keratoderma without evidence of cardiac involvement up to the age of 35 years, a diagnosis of Woolly hair-Palmoplantar keratoderma (WH-PPK) syndrome type 4 was made. The patient was started on topical keratolytics and oral acitretin therapy 25 mg once daily with close liver function and lipid profile monitoring. Remarkable improvement in palmoplantar keratoderma was noticed within 2 months of oral acitretin therapy [Figure 4]. The patient is on regular follow-up since.

Figure 4.

(a) Baseline photographs of palmoplantar keratoderma. (b) 2 months post acitretin therapy

WH-PPK syndrome encompasses a rare group of autosomal recessive diseases wherein hair and skin abnormalities are usually associated with potentially fatal cardiac complications. The four clinical syndromes described in literature have been summarized [Table 1]. Types 1-3 are associated with mutations of desmosomal proteins and present with life-threatening cardiac abnormalities while type 4 occurs due to mutation in steroid receptor coactivator (SRC)-interacting protein (non-desmosomal) presenting without cardiac involvement.

Table 1.

Woolly hair-Palmoplantar keratoderma syndromes

	Type 1 (NAXOS syndrome)[1]	Type 2 (CARVAJAL syndrome)[2]	Type 3 (NAXOS-like phenotype)	Type 4
Epidemiology	Presents during 2nd-3rd decade.	Presents early during childhood.	-	-
	1:1000 incidence in Greek islands
Clinical features	diffuse palmoplantar keratoderma, woolly hair, and recessive form of arrhythmogenic right ventricular cardiomyopathy	Striate keratoderma, woolly hair and dilated left ventricular cardiomyopathy.	Arrhythmogenic right ventricular cardiomyopathy, woolly hair and mild palmoplantar keratoderma	Woolly hair with palmoplantar keratoderma without cardiac abnormality
Gene mutation	JUP gene (encodes plakoglobin)	DSP gene (encodes desmoplakin)	DSC2 gene (encodes desmocollin-2)	KANK2 mutation
Prognosis	High risk of sudden cardiac death	Heart failure and sudden cardiac death can occur in adolescence	-	Good prognosis due to absence of cardiac involvement

Ramot et al.[3] reported 7 patients in two Arab families with consanguinity presenting with type 4 WH-PPK and demonstrated a common KANK2 mutation. All 7 patients were young, had striate PPK and occasional pseudoanhium of fifth toe. Another report by Mohanan et al.[4] described similar findings in a 3-year-old patient. However, the latter could well be Naxos or Carvajal syndrome as no genetic analysis was done to confirm type 4 WH-PPK. Our patient, on the other hand, presented in his late thirties with diffuse PPK with transgradiens and severe contractures along with woolly hair and no documented cardiac abnormality.

We believe that our patient represents the oldest surviving with type 4 WH-PPK syndrome, adding to the fact that a subset of patients with WH-PPK syndromes encode a non-desmosomal mutation (KANK2) have a good prognosis without the need for regular cardiac monitoring. To the best of our knowledge, this case is the first to be reported from the Indian subcontinent.

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