RESEARCH LETTER Progressive Spastic Paraplegia as a Feature of Tetrasomy 18p Annalisa Nucaro, 1 Ilaria Chillotti, 2 Tiziana Pisano, 2 Dario Pruna, 2 and Carlo Cianchetti 2 * 1 Istituto di Neurogenetica e Neurofarmacologia, CNR Cittadella Universitaria, Monserrato, Cagliari, Italy 2 Neuropsichiatria Infantile, Azienda Ospedaliero, Universitaria, Cagliari, Italy Received 22 February 2010; Accepted 31 May 2010 TO THE EDITOR: The tetrasomy 18p or isochromosome 18p [i(18p)] syndrome is associated with moderate to severe mental retardation, microceph- aly, dysmorphic features, and other abnormalities. ‘‘Spasticity’’ or ‘‘hypertonia’’ are frequently reported [about 80% of cases, Swingle et al., 2006], but not clearly defined; such definition is, however, essential in singling out the different nervous structures/pathways involved in the disorder. Here we present a case in which we determined that spasticity was due to a progressive spastic paraparesis, with the involvement of cortico-spinal and afferent somatosensory pathways. The clinical picture of this patient fits the basic features of genetic (or hereditary) spastic paraplegias (GSP), which are due to at least 30 different genetic loci, to date none identified in 18p (http:// www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book¼gene&part¼hsp). The propositus was the product of a second pregnancy of unrelated parents. The pregnancy was uncomplicated and the patient was born at 39 weeks of gestation. Apgar score was 8 at the 1st and 10 at the 5th minute. Weight at birth was 2,910 g, length 48 cm, and head circumference 33 cm, all in the range of 1 standard deviation (SD) below the mean. Clinical features during the neo- natal period included asymmetric face, hypertelorism, horizontal palpebral fissures, mandibular hypoplasia, low-set ears, hypoplasia of auricles, limited abduction of the hips, right club foot, cryptor- chidism, and small scrotum. Poor feeding was apparent within the first few days. At 13 and 23 months, height (respectively, 67 and 80 cm), weight (5 and 7.8 kg), and head circumference (41 and 44 cm) were all considerably below the 2 SD. There was a marked delay in motor (autonomic gait at 5 years) and language (first words at 7 years) milestones. Signs of spastic paraparesis (marked lower limb tendon hyperreflexia with Babinski sign) were first noted at about 4 years. At 13 years the patient has a severe mental retardation (WISC-III: QI < 40; QIV < 40, QIP < 40), without behavioral problems. Physical examination reveals microcephaly (49 cm, significantly below the 2 SD; mean values for age 54 cm), short stature (140.5 cm, 2,5 SD), weight 28.2 kg (1.93 SD). He has spastic paraparesis: bilateral hypertonic adduction of hips with equinovarus feet more severe at left, generalized tendon hyperreflexia and bilateral Babinski. He walks with tip-toe initial foot contact and slight hip adduction (gait had improved after botulinum toxin injection in the gastrocnemius muscles). Fingers of the hands are also in slight flexor hypertonus and dexterity of hand-finger movement is re- duced. Vibratory sensation is preserved. Bladder disturbances are not reported. Dysmorphic features (Fig. 1) included low anterior hair implant, oval facial shape, downslanting palpebral fissures, pointed nasal tip, high nasal bridge, long philtrum, small mouth with protruding lower lip, teeth malocclusion, high palate, low-set small ears, tapering fingers, clinodactyly, camptodactyly, kyphosis, micro- penis (3 cm), bilateral cryptorchidism, with normal left and very small right testicle at abdominal ultrasound examination. The cardiac investigation revealed ostium secundum interatrial defect. No other abnormalities of viscera were found. He never had seizures and denied bladder problems. The somato-sensory potentials (SSEPs) evoked by the stimula- tion of the tibial nerves showed an absence of the cortical response N35 in response to the stimulus at left, and an increased latency (47 msec) at right, with normal lumbar responses bilaterally. Stim- ulation of median nerves gave normal responses. Brain MRI, EEG, auditory and visual evoked responses were normal. *Correspondence to: Prof. Carlo Cianchetti, Neuropsichiatria Infantile, Universit  a, Via Ospedale 119, I-09124 Cagliari, Italy. E-mail: cianchet@unica.it Published online 3 August 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ajmg.a.33576 How to Cite this Article: Nucaro A, Chillotti I, Pisano T, Pruna D, Cianchetti C. 2010. Progressive spastic paraplegia as a feature of tetrasomy 18p. Am J Med Genet Part A 152A:2173–2175. Ó 2010 Wiley-Liss, Inc. 2173