Familial mandibuloacral dysplasia – a report of four cases

Abstract

Case 1 A 9‐year‐old girl born to second‐degree consanguineous parents was brought to the outpatient department with a history of pain in the feet and pigmentary changes on the skin of 4 years’ duration. Cutaneous examination revealed large symmetrical areas of mottled pigmentation (both hypo and hyper) with atrophy over the face, flexures, hands, and feet. There were multiple, small, keratotic papules (Fig. 1) over the back, joints, palms, and soles. Scalp examination revealed widened suture lines and multiple, soft, nodular swellings on the occipital region with sparse and short hair. There was also a small nodule on the scalp which discharged cheesy material and was suggestive of calcinosis cutis. The right index finger showed a broad terminal phalanx. Gynecologic examination revealed a small infantile uterus. The patient had normal dentition. 1 Keratotic papules on the buttocks Cases 2 and 3 Two brothers, aged 6 and 3 years, who were brought to the clinic for screening, also revealed similar skeletal and cutaneous changes, but with less intense pigmentation. Both had normal development of the genitalia. Case 4 After 4 years, another girl of 15 years of age was referred to us with complaints of inability to walk due to pain in the feet. The patient was born to second‐degree consanguineous parents and showed the same clinical features as those of Case 1, except for short stature (height, 138 cm) and a broad terminal phalanx on the left middle finger. This female patient also had an infantile uterus. All four patients were subjected to routine investigations, which were found to be within normal limits. Examination of the hair under potassium hydroxide mount did not reveal any abnormality. Skeletal surveys were performed for all patients. In Case 1, an X‐ray of the skull—anteroposterior (AP) and lateral view (Fig. 2) revealed frontal bossing of the cranial vault. Coronal, lambdoid, and sagittal sutures were widened, measuring 5, 5, and 7 mm, respectively. The cranial vault had a ground glass appearance and did not show outer and inner table differentiation. The metopic and mendosal sutures were seen. The sutures were seen as straight lines instead of serrated interdigitations. The occipital area showed only a sea of membranes with islands of ossified bones (Wormian bones). Platybasia was seen. The mandible was hypoplastic. A chest X‐ray revealed a narrow chest cavity with normal clavicles. An X‐ray of the spine was normal. An X‐ray of the pelvis showed increased acetabular angles, collapsed head of femur, and reduced shaft neck angle. An X‐ray of the hand showed popcorn calcification in the soft tissues. There was hypoplasia of the distal part of the terminal phalanx of the left index finger. An X‐ray of the foot also showed similar soft tissue calcification of the left big and little toes. 2 Lateral view of X‐ray of the skull showing multiple Wormian bones in the occipital region Skeletal surveys of the two other siblings revealed Wormian bones and widened suture lines, but were otherwise normal. A skel...

Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia

“…'Bony knots' on the phalanges and severe skin contractures were also peculiar features present in our patient. 'Bony knots' have only been rarely reported in patients with mandibuloacral dysplasia (18,19). Progeroid features have been previously described in patients with MAD and some of them were initially diagnosed as having Werner or progeroid syndrome (18,(20)(21)(22)(23)(24).…”

“…'Bony knots' have only been rarely reported in patients with mandibuloacral dysplasia (18,19). Progeroid features have been previously described in patients with MAD and some of them were initially diagnosed as having Werner or progeroid syndrome (18,(20)(21)(22)(23)(24). Recently, mutations in LMNA have been reported in patients with Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder characterized by features of premature ageing such as growth retardation, alopecia, atherosclerosis, sclerodermatous skin, and premature death during teenage years (25)(26)(27).…”

Mandibuloacral dysplasia caused by homozygosity for the R527H mutation in lamin A/C

“…Other affected individuals have differed in the extent of acro-osteolysis or in whether hypogonadism is present. [31][32][33] Individuals with Hoepffner-Dreyer-Rudiger syndrome 34 lack acro-osteolysis but otherwise phenotypically resemble MAD. Simha and Garg 19 proposed two variant forms of MAD which are distinguished by the pattern of body fat distribution: type A, with preferential accumulation of subcutaneous fat centrally, and type B, with generalised loss of subcutaneous fat.…”

What Syndrome Is This?

“…Wiedemann‐Rautenstrauch syndrome may be confused with progeria (Hutchinson‐Gilford progeria), which is not present at birth (9), and other progeroid syndromes (Table 1). These include De Barsy syndrome (10) and Cockayne syndrome (11), both with neurologic and ophtalmologic abnormalities; Berardinelli–Seip syndrome (12), which exhibits extreme muscularity, acanthosis nigricans; leprechaunism (13) and Hallerman–Streiff syndrome (14), both with characteristic, distinctive facies, mandibuloacral dysplasia (15), which is not present at birth and is associated with Wormian bones of the skull; carbohydrate deficient glycoprotein (CDG) syndrome type 1, which includes skin changes (“peau d’orange”) and episodes of failure of vital organ systems (16); and growth retardation, alopecia, pseudoanodontia, ocular manifestations (GAPO) syndrome, which has pseudoanodontia as a distinctive feature.…”