Inherited defects of adipose tissue dermatology ppt

Inherited defects of adipose tissue dermatology

1. GENETIC DISORDERS OF ADIPOSE TISSUE BY DR.MARYAM TAHIR PGR DERMATOLOGY

2. Selective loss of adipose tissue from various anatomical sites Vary from very small depressed areas to near complete absence of adipose tissue Clinical features common to all types of lipodystrophy include insulin‐resistance, hyperlipidaemia, liver disease and and increased metabolic rate CONGENITAL (FAMILIAL) LIPODYSTROPHIES:

3. Congenital generalized lipodystrophies Familial partial lipodystrophies TYPES OF CONGENITAL LIPODYSTROPHIES:

4. (a) Generalized lipoatrophy of the upper and lower limbs. (b) Severe lipoatrophy of the buttocks. (

5. Autosomal recessive conditions The earliest sign in the neonate is a virtual absence of fatty tissues and muscular appearance. Linear growth of an affected child significantly increased Insulin resistance and hypertriglyceridemia Acute pancreatitis CONGENITAL GENERALIZED LIPODYSTROPHIES:

6. Acanthosis nigricans Fatty infiltration of the liver leading to cirrhosis Hepatosplenomegaly with umbilical herniation. A pseudoacromegalic appearance Features similar to PCOS together with clitoromegaly and subfertility in females. Males have normal fertility Type 2 diabetes CONGENITAL GENERALIZED LIPODYSTROPHIES(cont.):

7. Clinical subtype Mode of inheritance Gene Clinical summary CGL1 AR AGPAT2 Generalized lipodystrophy, insulin resistance, acanthosis nigricans, muscular hypertrophy, hepatomegaly, diabetes, hypertriglyceridaemia CGL2 AR BSCL2 As above but more severe plus mild learning difficulties, sensorimotor neuropathy, secondary mitochondrial dysfunction, cardiomyopathy

8. CLINICAL SUBTYPE MODE OF INHERITENCE GENE CLINICAL SUMMARY CGL3 AR CAV1 As for CGL1 plus prominent veins, hirsutism, short stature, vitamin D resistance, hypocalcaemia CGL4 AR PTRF As for CGL1 plus congenital myopathy, cervical spine instabilty, cardiac arrhythmias and myopathy, pyloric stenosis

9. CLINICAL SUBTYPE MODE OF INHERITANCE GENE CLINICAL SUMMARY MAD TYPE A AR LMNA Lipodystrophy. Milder metabolic phenotype, Occasional progeroid features,Mandibular and clavicular hypoplasia and acro‐osteolysis. , cardiomyopathy MAD TYPE B AR ZMPSTE24 Generalized lipodystrophy. Milder metabolic phenotype,Progeroid appearence Bone changes as for type A. Skin atrophy, prominent superficial vessels, mottled hyperpigmentation, thin beaked nose, alopecia, delayed dentition, crowded teeth, late closure of cranial sutures, joint stiffness

10. MANDIBULOACRAL DYSPLASIA :

11. Autosomal recessive Mutation in BANF1 CLINICAL FEATURES: Generalized lipodystrophy Scoliosis Pulmonary hypertension Progeroid features NESTOR GUILLERMO PROGERIA SYNDROME:

12. Atypical distribution of adipose tissue which begins in late childhood or early adult life Gradual loss of adipose tissue from both the upper and lower limbs, as well as from the buttocks and trunk In some people,fat accumulates paradoxically on the face and neck Associated features: type 2 diabetes with acanthosis nigricans and hypertriglyceridaemia. Hirsutism and menstrual abnormalities Myopathy, Cardiomyopathy and Cardiac arrythmias FAMILIAL PARTIAL LIPODYSTROPHIES:

13. CLINICAL SUBTYPE MODE OF INHERITANCE GENE CLINICAL SUMMARY FPL1 AD Loss of subcutaneous adipose tissue from the extremities FPL2 AD LMNA From puberty there is a loss of subcutaneous adipose tissue from the extremities and trunk (but not the face and neck) FPL3 AD PPARG Loss of limb and gluteal fat with normal subcutaneous abdominal/visceral fat. FPL4 AD AKT2 Loss of subcutaneous adipose tissue from the limbs FPL5 AD PLIN1 Severe hyper‐triglyceridaemia

14. CLINICAL SUBTYPE GENE MODE OF INHERITANCE CLINICAL SUMMARY Hutchinson–Gilford progeria syndrome LMNA AR Short stature, low body weight, partial or generalized lipodystrophy, generalized alopecia, scleroderma, decreased joint mobility, osteolysis, ageing of facial features, insulin resistance Atypical progeroid syndrome LMNA AR Progeroid features (as above) with variable loss of subcutaneous fat, insulin resistance SHORT syndrome PIK3R1 AD Short stature, developmental delay,lipodystrophy,ocular depression, iris hypoplasia, deafness,delayed dentition,hyperextensibility,inguinal hernia

15. Hutchinson–Gilford Progeria syndrome

16. SHORT SYNDROME:

17. Mostly polygenic but single gene disorders also present Monogenic obesity may be with or without cutaneous features Onset in childhood Excess body weight contributes to psychological problems, cancers, metabolic disease, cardiovascular problems, musculoskeletal disorders and dermatological conditions HEREDITARY OBESITY:

18. SYNDROME MODE OF INHERITANCE GENE OTHER CLINICAL FEATURES Leptin receptor deficiency AR LEPR Hyperleptinaemia, hypogonadism Melanocortin-4 receptor deficiency AD MC4R Accelerated growth, tall stature BDNF deficiency AD BDNF Developmental delay, memory problems,hyperactivity, reduced pain sensation TrkB deficiency AD NTRK2 Developmental delay, memory problems,hyperactivity, reduced pain sensation MONOGENIC OBESITY WITHOUT CUTANEOUS FEATURES:

19. SYNDROME MODE OF INHERITANCE GENE OTHER CLINICAL FEATURES SIM1 deficiency AR SIM1 Developmental delay Bardet-Biedel syndrome AR BBS1-16, ARL6, MKKS, MKS1, CEP290 Developmental delay,polydactyly,retinopathy,renal anomalies Carpenter syndrome AR RAB23, 6p11 Craniosynostosis, polysyndactyly, cardiac defects Börjeson-Forssman- Lehman syndrome X linked recessive PHF6, Xq27.3 Developmental delay, hypogonadism, epilepsy, facial swelling, narrow palpebral fissures, large ears

20. SYNDROME MODE OF INHERITANCE GENE OTHER CLINICAL FEATURES SH2B deficiency Copy number variation SH2B Insulin resistance, hyperinsulinaemia MOMO syndrome AR ? Short s tature,macrosomia, macrocephaly, retinal coloboma and nystagmus, downward slant of the palpebral fissures, mental retardation and delayed bone maturation MORM syndrome AR INPP5E Mental retardation, truncal obesity, retinal dystrophy and micropenis Cohen syndrome ? VPS13B Developmental delay, delayed puberty, short stature,scoliosis,Insulin resistance, down-sloping palpebral fissures, maxillary hypoplasia, micrognathia, high-arched palate, dental anomalies, retinopathy, neutropenia

21. BARDET BIEDEL SYNDROME:

22. CARPENTER SYNDROME:

23. MOMO SYNDROME

24. COHEN SYNDROME:

25. Obesity is inherited with dermatological signs as part of a syndrome EXAMPLES: Pro‐opiomelanocortin and prohormone convertase 1 deficiency Prader-Willi sydrome MONOGENIC OBESITY WITH CUTANEOUS FEATURES:

26. AR mutation in POMC gene ACTH, alpha MSH, Beta endorphin Clinical features : Obesity Red hair Fair skin POMC DEFICIENCY:

27. AR mutation in PSK1 gene CLINICAL FEATURES: Obesity Hypogonadotrophic hypogonadism Glucocorticoid deficiency Post prandial hypoglycemia PC1 DEFICIENCY:

28. Inactivation or deletion of a paternally (not maternally) inherited chromosome region, 15q11‐q13 CLINICAL FEATURES: Obesity Acanthosis nigricans Hypopigmentation Decreased pain sensitivity Chronic sores and scars PRADER WILLI SYNDROME:

29. PRADER WILLI SYNDROME:

30. Striae Hirsutism Cutaneous infection Psoriasis Atopic eczema Keratosis pilaris Irritant contact dermatitis Skin cancer Hidradenitis suppurativa Scleredema Livedo reticularis Pilonidal sinus Skin complications of primary obesity:

31. Mutation in PIK3CA CL: Congenital lipomatous overgrowth V: Vascular malformation E : Epidermal nevi S: Skeletal/ Spinal CLOVES SYNDROME:

32. SYNDROME MOI GENE CLINICAL SUMMARY Alpha‐1‐antitrypsin deficiency AR SERPINA1 Emphysema, liver disease, glomerulonephritis,panniculitis, arthritis, vasculitis, uveitis Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome AR PSMB8 Failure to thrive, joint contractures, muscular atrophy,panniculitis‐induced lipodystrophy, loss of facial fat, acral annular erythematous plaques, elevated temperature, inflammatory markers, microcytic anaemia Autoimmune lymphoproliferative syndrome (Canale–Smith syndrome) AD TNFSF6,TNFRSF6 Lymphadenopathy, hepatosplenomegaly, autoimmune anaemia and thrombocytopenia, urticaria, vasculitis, panniculitis, increased risk of malignant lymphoma HEREDITARY PANNICULITIS:

33. Hereditary panniculitis caused by homozygous ZZ α1‐antitrypsin deficiency .

34. Mutation in PIT1 gene Persistent accumulation of fat in lower limbs Association with growth hormone deficiency,hypothyroidism and hypoprolactinaemia FAMILIAL LIPOEDEMA: