Prader-Willi syndrome (PWS) is characterized by hypotonia, obesity, hypogonadism, short stature, small hands and feet, mental deficiency, a characteristic face, and an interstitial deletion of the proximal long arm of chromosome 15 in about one-half of the patients. The incidence is estimated to be about 1 in 25,000, and PWS is the most common syndromal cause of human obesity. DNA abnormalities, usually deletions or duplications of chromosome 15, have been identified in individuals with PWS with or without recognizable chromosome 15 deletions. Paternal origin of the chromosome 15 deletion by cytogenetic and DNA studies has been found in nearly all PWS individuals studied. No cytogenetic evidence for chromosome breakage has been identified, although an environmental cause (e.g., paternal hydrocarbon-exposed occupations) of the chromosome 15 abnormality has been proposed. PWS patients with the chromosome 15 deletion are more prone to hypopigmentation compared with PWS individuals with normal chromosomes, but no other clinical differences are consistently identified between those with and without the chromosome deletion. Anthropometric, dermatoglyphic, and other clinical findings indicate homogeneity of PWS patients with the chromosome deletion and heterogeneity of the nondeletion patients. A review of our current understanding of the major clinical, cytogenetic, and DNA findings is presented, and clinical manifestations and cytogenetic abnormalities are summarized from the literature.

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Prader-Willi syndrome: Current understanding of cause and diagnosis

Solar-induced cutaneous changes are more prevalent and profound in older persons and, thus, are often inappropriately attributed to the aging process, per se. Structural and functional alterations caused by intrinsic aging and independent of environmental insults are now recognized in the skin of elderly individuals. Structurally the aged epidermis likely becomes thinner, the corneocytes become less adherent to one another, and there is flattening of the dermoepidermal interface. The number of melanocytes and Langerhans cells is decreased. The dermis becomes atrophic and it is relatively acellular and avascular. Dermal collagen, elastin, and glycosaminoglycans are altered. The subcutaneous tissue is diminished in some areas, especially the face, shins, hands, and feet, while in others, particularly the abdomen in men and the thighs in women, it is increased. The number of eccrine glands is reduced and both the eccrine and apocrine glands undergo attenuation. Sebaceous glands tend to increase in size but paradoxically their secretory output is lessened, The nail plate is generally thinned, the surface ridged and lusterless, and the lunula decreased in size. There is a progressive reduction in the density of hair follicles per unit area on the face and scalp, independent of male-pattern alopecia. The hair shaft diameter is generally reduced but in some areas, especially the ears, nose, and eyebrows of men and the upper lip and chin in women, it is increased as vellus hairs convert to cosmetically compromising terminal hairs. Functional alterations noted in the skin of elderly persons include a decreased growth rate of the epidermis, hair, and nails, delayed wound healing, reduced dermal clearance of fluids and foreign materials, and compromised vascular responsiveness. Eccrine and apocrine secretions are diminished. The cutaneous immune and inflammatory responses are impaired, particularly cell-mediated immunity. Clinical correlates of these intrinsic aging changes of the skin include alopecia, pallor, xerosis, an increased number of benign and malignant epidermal neoplasms, increased susceptibility to blister formation, predisposition to injury of the dermis and underlying tissues, delayed onset and resolution of blisters and wheals, persistent contact dermatitis, impaired tanning response to ultraviolet light, increased risk for wound infections, prolongation of therapy necessary for onychomycosis, and thermoregulatory disturbances.

https://www.jaad.org/article/S0190-9622(86)70208-9/pdf

Structural and functional changes of normal aging skin

Lymphocyte subset reference ranges in adult Caucasians.

Assessment of protein energy malnutrition in older persons, Part II: Laboratory evaluation.

Allogeneic marrow grafting for treatment of aplastic anemia.

Leukæmic transformation of engrafted human cells in vivo

Smaller g chromosome in irradiated man

T, B and "Null" lymphocytes were determined in the peripheral blood of 98 adults, 26 of them were between 20 to 40 years of age and 72 between 60 to 96 years of age. The total number of lymphocytes were about the same in both groups. The percent and absolute number of T cells decreased significantly in the aged. Although the percent of B lymphocytes increased with age, the absolute number of B lymphocytes remained about the same.

B and T lymphocytes in man. IV. Circulating B, T and "null" lymphocytes in aging population.

Pseudodiploid chromosomal pattern in chronic lymphocytic leukemia.

If leukemia is caused by an "agent" which can pass through the placenta, it could produce leukemic transformation in the maternal cells. Cytogenetic studies were carried out in 5 acute lymphoblastic leukemic children and their parents. Significant abnormalities were found in 3 of the fathers, 4 of the mothers, and all the leukemic children. All but one abnormal metaphase from the mothers of the 2 leukemic boys had a XX sex pattern, indicating that these abnormal metaphases originated in the mother and probably were caused by a chromosomal breaking agent. The abnormal metaphases found in the fathers suggests that they too were exposed to this agent. Therefore, this agent must be present in the immediate environment, and this can pass from the material circulation to the fetus through the placenta and effect the fetus cells. The failure of the infant to eradicate these abnormal cells results in the phenotypical expression of clinical leukemia.

Kong-Oo Goh

Papers

Leukæmic transformation of engrafted human cells in vivo

Smaller g chromosome in irradiated man

B and T lymphocytes in man. IV. Circulating B, T and "null" lymphocytes in aging population.

Pseudodiploid chromosomal pattern in chronic lymphocytic leukemia.

Evidence of clastogens in acute leukemia. Chromosomal abnormalities in healthy parents of congenital leukemic patients.