Familial progressive hyper- and hypopigmentation and malignancy in two families with new mutations in KITLG.

BACKGROUND: Familial progressive hyper- and hypopigmentation (FPHH) is an autosomal dominant skin condition presenting in childhood with generalized macular dyspigmentation, usually reported in patients of East Asian origin. It overlaps phenotypically with other dyschromatoses, but can now be distinguished by mutations in the KIT ligand gene (KITLG). AIM: We report two unrelated white families with similar phenotypic presentations of FPHH developing in early childhood in several generations. METHODS: Sanger sequencing of the exons and flanking introns of KITLG was performed. RESULTS: This identified a new heterozygous missense mutation in each family (p.Thr34Asn and p.Val37Gly, respectively). Of the six affected individuals examined by us, two had cancer: a 62-year-old man in family 1 had developed two primary melanomas and a pharyngeal carcinoma, and a 42-year-old woman in family 2 had developed thyroid carcinoma. All had unusually sparse lateral eyebrows, a finding not previously reported in this condition. CONCLUSIONS: We summarize the genetic spectrum of the dyschromatoses and discuss a possible increased risk of malignancy in FPHH.

Phacomatosis pigmentokeratotica associated with a suprasellar dermoid cyst and leg hypertrophy.

Phacomatosis pigmentokeratotica (PP) is a mosaic disorder that represents a distinct epidermal naevus syndrome. Its defining features are an epidermal naevus that is usually of the sebaceous type and a speckled lentiginous naevus arranged in a chequerboard pattern. In addition, there are neurological, ophthalmological and skeletal abnormalities, including limb hemiatrophy with muscular weakness, ptosis, seizures and ipsilateral segmental hyperaesthesia and hyperhidrosis. We report a 44-year-old man with an extensive epidermal naevus and an ipsilateral speckled lentiginous naevus. He also had ipsilateral right leg hypertrophy and a suprasellar dermoid cyst with associated neurological abnormalities. We propose that this case represents an unusual example of PP.

Epidermal naevus in Proteus syndrome showing loss of heterozygosity for an inherited PTEN mutation.

A 3-year-old boy with Proteus syndrome has a novel germline p.Y68D mutation of the PTEN gene inherited from his mother who has Cowden syndrome. In addition, DNA extracted from curettings of his widespread epidermal naevus shows loss of heterozygosity for this mutation. To our knowledge, this has not been described before.

Management of melanoma metastasis to the breast: case series and review of the literature.

BACKGROUND: Metastases to the breast from extramammary cancers are rare; melanoma is one of the malignancies that can metastasize to the breast. OBJECTIVES: To examine the records of a series of patients with a previous diagnosis of melanoma and a metastasis to the breast, and review the published literature of this condition. METHODS: We report details of eight female patients with breast metastases from melanoma seen over a 36-month period from 2001. All patients were female aged 28-84 years (median 58). The breast lump was investigated by core-cut biopsy or fine needle aspiration, with or without a mammogram. RESULTS: The time between diagnosis of the primary melanoma and the occurrence of a breast metastasis ranged from 13 to 180 months (median 62). In three patients the breast lump was the first sign of recurrence of melanoma. In three patients melanoma had previously relapsed in regional lymph nodes and in two patients it had already relapsed as locoregional and distant subcutaneous metastases before metastasizing to the breast. In two patients presenting via the breast clinic, the lump was subsequently confirmed on excision to be melanoma in an intramammary lymph node. In seven patients, a lumpectomy was performed after histological confirmation; one of these also had a level 1-3 axillary dissection. The eighth patient deteriorated clinically before further surgery was possible. Six patients developed further metastases within 1-5 months of breast lump detection. In one case a second 9 mm breast lump in the deeper tissue of the same breast was detected on a computed tomography scan and has been removed using stereotactic surgery. Four patients have died. CONCLUSIONS: Presentation is usually with a palpable mass without skin changes. Investigation must include histology or cytology to confirm the diagnosis. Management of melanoma metastasis to the breast is discussed; in this series it was surgical unless there were many metastases.

Study of patient-reported morbidity following V-beam pulsed-dye laser treatment of port wine stains.

The V-beam pulsed-dye laser (PDL) (595 nm) has gained popularity in the treatment of port wine stains (PWS). It uses longer pulse durations than the standard flashlamp-pumped pulsed-dye laser (FPDL) (585 nm) and has an in-built cooling system to protect the epidermis. This should, theoretically, reduce the treatment-associated side effects, including discomfort. The aim of this questionnaire-based study was to confirm the clinical impression that V-beam PDL is well tolerated. The results were compared with a historical group of 62 PWS patients treated with FPDL. Fifty-one patients took part in the current study. Only 35.7% (vs. 81% in the historical comparison group) required topical anaesthetic prior to laser treatment. A shortening in the duration of bruising (8 vs. 10 days) and of symptoms such as burning and tightness (3 vs. 10 days) was recorded. Lifestyle change after treatment was recorded by fewer patients (39 vs. 57%). We conclude that V-beam PDL is better tolerated than FPDL when used at therapeutic levels in patients with PWS.

Seasonal occurrence of impetigo: a retrospective 8-year review (1996-2003).

Impetigo, a common skin infection, has shown seasonal variation in African, Australian and Indian studies. We investigated seasonal variation of impetigo in a UK paediatric population. A total of 1552 children with impetigo were seen in the Accident and Emergency (A&E) department between 1996 and 2003. The number of impetigo cases was always higher in late summer than in winter, and furthermore, increased year on year. These changes could not be accounted for by variation in total patient numbers seen in A&E, and suggest a correlation between impetigo frequency and climatic temperature. Possible reasons for these findings include exposed skin due to loose clothing in the summer leading to more skin-to-skin contact and minor trauma.

Mild ichthyosis in a 4-year-old boy with multiple sulphatase deficiency.

We report a 4-year-old boy with multiple sulphatase deficiency (MSD). His early health was good. By the end of his first year there were concerns about developmental delay but by 26 months he showed clear evidence of regression in that he was barely able to sit unsupported and had lost all fine motor and communication skills. At that time he also had widespread mild ichthyosis that cleared completely with the use of emollients. The neurological deterioration suggested a diagnosis of metachromatic leucodystrophy, and a reduction in the leucocyte arylsulphatase A activity was detected. The ichthyosis suggested steroid sulphatase deficiency, and a reduction in the leucocyte steroid sulphatase activity was detected. The enzyme deficiency was much less marked for steroid sulphatase than for arylsulphatase A in this boy. This diversity in enzyme activities is typical of MSD and correlates with the mild ichthyosis in this child. This case shows that even mild ichthyosis should prompt measurement of steroid sulphatase activity in a child of either sex with unexplained neurological deterioration.