More Than Skin Deep: Genetics, Clinical Manifestations, and Diagnosis of Albinism

Although albinism may be considered a simple diagnosis, its clinical manifestations, which include hypopigmenta- tion of the skin, hair, and eyes and ocular abnormalities such as nystagmus and reduced visual acuity, are often subtle and initially missed. In oculocutaneous albinism, there is wide phenotypic variability, which correlates with specific mutations in genes with roles in melanin biosynthesis. Additionally, syndromic forms of albinism such as Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Griscelli syndrome are associated with serious complications such as bleeding abnormalities, lysosomal storage defects, immunodeficient states, and progressive neurologic defects, which all can result in mortality. It is critical to confirm a suspicion of albinism and perform an appropriate workup involving molecular testing in order to establish a diagnosis. Given the various subtypes of oculocutaneous albinism and the life-threatening complications in syndromic forms of albinism, a diagnosis permits proper genetic counseling and timely implementation of necessary screenings and treatments. Recommendations regarding sun exposure and treatment of ocular abnormalities are imperative in oculocutaneous albinism, and preventive therapies should be implemented in syndromic forms. With knowledge of the differential in conjunction with the execution of simple diagnostic tests, many of these complications can be predicted and consequently ameliorated or prevented.

Creation and characterization of BAC-transgenic mice with physiological over-expression of epitope-tagged RCAN1 (DSCR1)

The chromosome 21 gene RCAN1, encoding a modulator of the calcineurin (CaN) phosphatase, is a candidate gene for contributing to cognitive disability in people with Down syndrome (DS; trisomy 21). To develop a physiologically relevant model for studying the biochemistry of RCAN1 and its contribution to DS, we generated bacterial artificial chromosome-transgenic (BAC-Tg) mouse lines containing the human RCAN1 gene with a C-terminal HA-FLAG epitope tag incorporated by recombineering. The BAC-Tg was expressed at levels only moderately higher than the native Rcan1 gene; approximately 1.5-fold in RCAN1BAC-Tg1 and 2-fold in RCAN1BAC-Tg2. Affinity purification of the RCAN1 protein complex from brains of these mice revealed a core complex of RCAN1 with calcineurin (CaN), glycogen synthase kinase 3-beta (Gsk3b), and calmodulin, with sub-stoichiometric components including LOC73419. The BAC- Tg mice are fully viable, but long-term synaptic potentiation (LTP) is impaired in proportion to BAC-Tg dosage in hippocampal brain slices from these mice. RCAN1 can act as a tumor suppressor in some systems, but we found that the RCAN1 BAC-Tg did not reduce mammary cancer growth when present at a low copy number in Tp53;WAP-Cre mice. This work establishes a useful mouse model for investigating the biochemistry and dose-dependent functions of the RCAN1 protein in vivo

MEDICAL REVIEW More than skin deep: Genetics, clinical manifestations, and diagnosis of albinism

ABSTRACT Although albinism may be considered a simple diagnosis, its clinical manifestations, which include hypopigmentation of the skin, hair and eyes and ocular abnormalities such as nystagmus and reduced visual acuity, are often subtle and initially missed. In oculocutaneous albinism, there is wide phenotypic variability, which correlates with specific mutations in genes with roles in melanin biosynthesis. Additionally, syndromic forms of albinism such as Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Griscelli syndrome are associated with serious complications such as bleeding abnormalities, lysosomal storage defects, immunodeficient states, and progressive neurologic defects, which all can result in mortality. It is critical to confirm a suspicion of albinism and perform an appropriate work-up involving molecular testing in order to establish a diagnosis. Given the various subtypes of oculocutaneous albinism and the life-threatening complications in syndromic forms of albinism, a diagnosis permits proper genetic counseling and timely implementation of necessary screenings and treatments. Recommendations regarding sun exposure and treatment of ocular abnormalities are imperative in oculocutaneous albinism, and preventative therapies should be implemented in syndromic forms. With knowledge of the differential in conjunction with the execution of simple diagnostic tests, many of these complications can be predicted and consequently ameliorated or prevented

Diffuse sebaceous-gland hyperplasia

Diffuse sebaceous-gland hyperplasia is a rarevariant of sebaceous-gland hyperplasia that isdistinct from the well-known circumscribed type.The term presenile sebaceous hyperplasia has beenutilized to describe this entity that is distinguishedby specific features, which include confluence oflesions that results in the formation of large plaqueson the face, the sparing of periorificial regions, andhighly functional glandular hyperplasia that resultsin excessive sebaceous secretion. We present a43-year-old woman with monomorphous, skincoloredand yellow, smooth 1- to-3-mm papules,some with central umbilication, that spare theperiorificial zones. Histopathologic examination wassuggestive of diffuse sebaceous-gland hyperplasia.Differential diagnosis of this condition is broad andincludes syndromes that are associated with multiplefacial papules and malignant conditions, such asMuire-Torre syndrome and Cowden syndrome. Itis important to be aware of this condition in orderto consider appropriate treatment options, such asisotretinoin and to avoid unnecessary diagnostictests

Diffuse sebaceous-gland hyperplasia

Diffuse sebaceous-gland hyperplasia is a rarevariant of sebaceous-gland hyperplasia that isdistinct from the well-known circumscribed type.The term presenile sebaceous hyperplasia has beenutilized to describe this entity that is distinguishedby specific features, which include confluence oflesions that results in the formation of large plaqueson the face, the sparing of periorificial regions, andhighly functional glandular hyperplasia that resultsin excessive sebaceous secretion. We present a43-year-old woman with monomorphous, skincoloredand yellow, smooth 1- to-3-mm papules,some with central umbilication, that spare theperiorificial zones. Histopathologic examination wassuggestive of diffuse sebaceous-gland hyperplasia.Differential diagnosis of this condition is broad andincludes syndromes that are associated with multiplefacial papules and malignant conditions, such asMuire-Torre syndrome and Cowden syndrome. Itis important to be aware of this condition in orderto consider appropriate treatment options, such asisotretinoin and to avoid unnecessary diagnostictests

Photodistributed granuloma annulare

Annular elastolytic giant cell granuloma (AEGCG) is a controversial entity that is considered by many to be a variant of granuloma annulare (GA). The majority of cases of AEGCG occur in Caucasian women (3:2) between the ages of 40 and 70, with the distribution of the mostly annular lesions favoring exposed areas of skin and rarely involving covered skin. The most common systemic association has been with diabetes mellitus. We present a 52-year-old woman with an asymptomatic, annular, erythematous, photodistributed eruption of two-years duration. As part of her evaluation, it was detected that she had a hemoglobin A1C of 10.3% and a diagnosis of diabetes mellitus was made. We review the literature on the clinical and histopathologic features of GA and AEGCG and the overlap between these entities

Primary cutaneous smoldering adult T-cell leukemia/ lymphoma

HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches

Photodistributed granuloma annulare

Annular elastolytic giant cell granuloma (AEGCG) is a controversial entity that is considered by many to be a variant of granuloma annulare (GA). The majority of cases of AEGCG occur in Caucasian women (3:2) between the ages of 40 and 70, with the distribution of the mostly annular lesions favoring exposed areas of skin and rarely involving covered skin. The most common systemic association has been with diabetes mellitus. We present a 52-year-old woman with an asymptomatic, annular, erythematous, photodistributed eruption of two-years duration. As part of her evaluation, it was detected that she had a hemoglobin A1C of 10.3% and a diagnosis of diabetes mellitus was made. We review the literature on the clinical and histopathologic features of GA and AEGCG and the overlap between these entities