A novel syndrome of mandibular hypoplasia, deafness, and progeroid features associated with lipodystrophy, undescended testes, and male hypogonadism.
BACKGROUND
Mandibuloacral dysplasia (MAD) is an autosomal recessive progeroid disorder associated with type A (partial) or B (generalized) lipodystrophy and is due to mutations in lamin A/C (LMNA) or zinc metalloproteinase (ZMPSTE24) genes.


OBJECTIVE
The objective of the study was to report a novel syndrome with some overlapping features with MAD.


RESULTS
We report seven patients with mandibular hypoplasia, deafness, progeroid features (MDP), and associated lipodystrophy. These patients have similar features to MAD patients such as hypoplastic mandible, beaked nose, stiff joints, and sclerodermatous skin. However, the patients did not harbor any disease causing variants in LMNA or ZMPSTE24 and showed distinct characteristics such as sensorineural hearing loss and absence of clavicular hypoplasia and acroosteolysis. All males with MDP had undescended testes and were hypogonadal. One adult female showed lack of breast development. Skinfold thickness, dual-energy X-ray absorptiometry and whole-body magnetic resonance imaging for body fat distribution revealed a lack of lipodystrophy in a prepubertal female but a progressive loss of sc fat presenting with partial lipodystrophy in young adults and generalized lipodystrophy in older patients.


CONCLUSIONS
Patients with MDP syndrome have a few overlapping but some distinct clinical features as compared with MAD, suggesting that it is a novel syndrome. The molecular basis of MDP syndrome remains to be elucidated.
Shastry
Savitha
S
Division of Nutrition and Metabolic Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-8537, USA.
Simha
Vinaya
V
Godbole
Koumudi
K
Sbraccia
Paolo
P
Melancon
Serge
S
Yajnik
Chittaranjan S
CS
Novelli
Giuseppe
G
Kroiss
Matthias
M
Garg
Abhimanyu
A
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002648:Child; D003456:Cryptorchidism / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis; D003638:Deafness / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000150:complications* / Q000151:congenital / Q000175:diagnosis / Q000235:genetics; D008060:Lipodystrophy / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008334:Mandible / Q000002:abnormalities* / Q000473:pathology; D008875:Middle Aged; D011371:Progeria / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D013577:Syndrome; D055815:Young Adult