Clinical Imaging 30

The high-resolution chest CT findings in an adult with

Melnick–Needles syndrome

Derrick Harpera, David A. Bloomb,4, James A. Rowleyc, Ayman Soubanic, Wilbur L. Smithd

aDepartment of Radiology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USAbDepartment of Radiology, William Beaumont Hospital, 3601 West Thirteen Mile Rd., Royal Oak, MI 48073, USA

cDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine,

4201 St. Antoine, UHC-4C, Detroit, MI 48201, USAdDepartment of Radiology, Wayne State University School of Medicine, 4201 St. Antoine, DRH 3L-8, Detroit, MI 48201, USA

Received 15 January 2006; accepted 16 March 2006

Abstract

Melnick–Needles syndrome is an X-linked dominant skeletal dysplasia in which patients often succumb at an early age to chronic

pulmonary disease. Radiographic findings of Melnick–Needles syndrome consist of characteristic bony abnormalities and interstitial lung

disease. We present the high-resolution computed tomographic (CT) findings in a 39-year-old survivor of Melnick–Needles syndrome. The

clinical and physical exam findings also demonstrate an association between Melnick–Needles syndrome and obstructive sleep apnea.

D 2006 Elsevier Inc. All rights reserved.

Keywords: Melnick–Needles; Computed tomography; Sleep apnea

1. Introduction

In 1966, Melnick and Needles [1] reported a distinctive

X-linked dominant bone dysplasia which included sclerosis

of the skull base and mastoids as well as multiple additional

bony anomalies. The osseous abnormalities involve the

majority of the axial and appendicular skeleton and include

bowing of the long tubular bones with metaphyseal flaring,

a ribbon-like appearance to the ribs, increased height of the

vertebral bodies with anterior and posterior scalloping, S-

shaped tibiae, and medial flaring of the clavicles [1–10].

The striking male/female ratio of the syndrome reflects that

it is almost always lethal in males, either in utero or very

early in the postnatal period [1–10]. There are suggestions in

the literature that these patients are at increased risk for

pulmonary disease, often the cause of early death [3–8].

0899-7071/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved.

doi:10.1016/j.clinimag.2006.03.032

4 Corresponding author. Department of Radiology, William Beaumont

Hospital, 3601 West Thirteen Mile Road, Royal Oak, MI 48073-6769,

USA. Tel.: +1 248 898 1961.

E-mail address: david.bloom@beaumont.edu (D.A. Bloom).

The pathogenesis of Melnick–Needles syndrome is

unknown, but it is thought to be a connective tissue disorder

[4,9–12]. Most of the cases described in the literature have

focused primarily on the plain film findings in pediatric

patients, with little on the adult manifestations of the

syndrome [8,10]. The association with chronic pulmonary

disease has been previously suggested, but the imaging

details of these findings are few [9]. Our case demonstrates

the high-resolution chest CT findings of interstitial lung

disease in a symptomatic adult patient with Melnick–

Needles syndrome. Our case also indicates that the skeletal

manifestations of Melnick–Needles syndrome appear to

remain stable into adulthood. The clinical and physical exam

findings also demonstrate an association between Melnick–

Needles syndrome and obstructive sleep apnea [13].

2. Case report

A 39-year-old woman presented to the pulmonary clinic

complaining of a 5-year history of progressive dyspnea on

(2006) 350–353

Fig. 1. Posteroanterior (A) and lateral (B) radiographs of the chest

demonstrate the typical bony findings of Melnick–Needles syndrome,

including metaphyseal abnormalities, ribbon-like ribs, and vertebral

body scalloping.

Fig. 2. The initial topogram for the contrast enhanced chest CT, showing the

additional bony changes of Melnick–Needles syndrome.

D. Harper et al. / Clinical Imaging 30 (2006) 350–353 351

exertion. The dyspnea was associated with congestion and

wheezing, which were precipitated by changes in weather

and exposure to fumes. She complained of a postnasal drip

but denied cough, sputum production, or hemoptysis. She

was currently not on any medications. The past medical

history revealed that the patient was a nonsmoker and had a

history of pneumonia 15 years earlier.

The patient reported loud, habitual snoring, witnessed

apnea, and mild daytime sleepiness and fatigue. The family

history was noncontributory, with no history of Melnick–

Needles syndrome in other family members. The physical

examination was notable for short stature with micro-

gnathia, a small and crowded oropharynx, and kyphosco-

liosis. The lungs were clear to auscultation, and the cardiac

examination was within normal limits. Her oxygen satu-

ration was 83% on room air and she had a body mass index

of 22.3 kg/m2. The patient was begun on 2 L/min oxygen

via nasal cannula for the hypoxia and a nasal steroid for the

postnasal drip.

Pulmonary function tests were then obtained. The forced

expiratory volume in 1 s (FEVL) was 0.35 L (17% predicted),

and the forced vital capacity (FVC) was 0.42 L (16%) with a

FEVL/FVC ratio of 83%. There was a 17% increase in FEV1

and a 20% increase in FVC after nebulized bronchodilator.

Total lung capacity was 1.94 L (51%) and the residual volume

1.5 L (132%). Diffusing capacity was 20% of predicted. The

pulmonary function tests were interpreted as severe restric-

tive disease with a probable obstructive component.

An echocardiogram was performed to evaluate for right-

sided heart failure. There was borderline left ventricular

hypertrophy but normal function, with an ejection fraction

of 65%. There was no evidence of right-sided cardiac

disease or pulmonary hypertension.

An overnight sleep study demonstrated severe obstruc-

tive sleep apnea with an apnea–hypopnea index of 150/h,

present in all positions and all stages of sleep. The majority

of the night was spent with an oxygen saturation between

80% and 89%. The patient subsequently underwent positive

pressure titration and was titrated to a bilevel positive

Fig. 3. The topogram taken after the initial contrast CT for planning of the

high-resolution images demonstrates left hydroureteronephrosis (arrows).

D. Harper et al. / Clinical Imaging 30 (2006) 350–353352

pressure device with an inspiratory pressure of 20 cm H2O

and an expiratory pressure of 12 cm H2O.

Chest radiographs demonstrated bibasilar linear opacities,

increased interstitial markings, diminished lung volumes, and

bilateral pleural thickening. The bones were demineralized

and there were ribbon-like ribs and hypoplastic scapulae. The

humeri showed metaphyseal flaring and bowing. There was

kyphoscoliosis of the thoracolumbar spine with increased

vertebral body height as well as anterior and posterior

vertebral scalloping. The clavicles were severely hypoplastic

(Fig. 1A, B). The scout images for the CT showed flaring of

the iliac wings, with constriction of the pelvic inlet (Fig. 2),

and left hydroureteronephrosis (Fig. 3). High-resolution CT

images revealed predominantly bibasilar abnormalities, with

parenchymal bands of opacity that were subpleural in

location, pleural thickening but no definite pleural-based

masses, thickened interlobular septae, and a mosaic pattern

(Fig. 4A–C).

On follow-up, the patient is doing clinically well with

oxygen used only when needed. She has had some resolution

of her sleep apnea with a very good response to positive

pressure, including more refreshed sleep and decreased

excessive daytime sleepiness.

Fig. 4. (A–C) Multiple high-resolution CT images demonstrate chronic

pulmonary findings, including parenchymal bands of opacity (arrowheads),

pleural thickening (open arrows), thickened interlobular septae (arrows),

and a mosaic pattern suggesting altered regional perfusion and air trapping.

3. Discussion

Melnick–Needles syndrome (osteodysplasty) is a rare

skeletal dysplasia with X-linked dominant transmission that

is typically lethal in males [1–10]. The genetic defect is felt

to be a mutation in the gene encoding filamin A. The

diagnosis of Melnick–Needles syndrome is characterized by

distinct facial findings in combination with other clinical

features and a characteristic radiographic pattern [1–10].

While the differential diagnosis includes entities such as

frontometaphyseal dysplasia, precocious osteodysplasty,

D. Harper et al. / Clinical Imaging 30 (2006) 350–353 353

oto-palato-digital syndrome type II, and Hajdu–Cheney

syndrome, the diagnosis can be confidently made based

on the clinical and radiographic features, especially in the

hands of an experienced geneticist. Clinically, patients can

present with failure to thrive, recurrent pulmonary infec-

tions, symptoms related to pulmonary hypertension, bone

pain, and manifestations of obstructive uropathy [2–8,12].

These patients may also suffer from congenital heart disease

[3–9]. Patients often die at an early age secondary to

complications of chronic pulmonary disease [6–10].

Our case is unique because it is an adult presentation of

this disorder and well delineates the high-resolution chest CT

findings of the Melnick–Needles syndrome. These patients

have an increased risk of chronic pulmonary disease and

subsequent pulmonary hypertension, of uncertain etiology

[6,9]. Some have proposed that the small thoracic cage

places these patients at risk for restrictive lung disease,

chronic respiratory tract infections, and then pulmonary

hypertension [6]. Our case report is the first which

demonstrates chronic interstitial lung disease in an adult

patient with Melnick–Needles syndrome using high-reso-

lution chest CT. The high-resolution CT shows bibasilar

interstitial abnormalities with thickened interlobular septae, a

mosaic pattern suggestive of patchy air trapping with overall

diminished lung volumes, and pleural thickening. Possible

etiologies for these chronic lung changes include recurrent

respiratory tract infections with eventual pulmonary fibrosis.

It has been proposed that Melnick–Needles syndrome is a yet

undefined type of connective tissue disease, and like other

such disorders, the pulmonary findings may be a part of the

disease spectrum [1–11].

Urinary tract abnormalities have also been reported with

the Melnick–Needles syndrome, including hydrouretero-

nephrosis without vesicoureteric reflux or clear obstruction

(presumably congenital primary megaureter) [6,9,12]. It is

speculated that the urinary tract pathology is also related to

an underlying connective tissue disorder.

This case report is also important in that the patient clearly

had obstructive sleep apnea in addition to her pulmonary

disease. Obstructive sleep apnea is a syndrome characterized

by recurrent airway collapse associated with oxyhemoglobin

desaturations and arousals, and is most commonly seen in

obese patients [14]. However, a subset of patients with this

disorder has craniofacial abnormalities rather than obesity as

the risk factor [14]. In particular, many different congenital

and genetic syndromes, such as Pierre Robin sequence and

Treacher Collins syndrome, which demonstrate craniofacial

abnormalities, have been associated with obstructive sleep

apnea [13,15]. Many of these syndromes are characterized

by micrognathia and a small, bcrowdedQ oropharynx, both ofwhich were present in our patient. A previous patient with

Melnick–Needles syndrome was reported to need emergent

tracheostomy due to sleep apnea [13]. Given the character-

istic craniofacial abnormalities seen with Melnick–Needles

syndrome, we suggest that patients with this disorder should

be carefully investigated for obstructive sleep apnea.

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