Coutinho P, Barros J, Zemmouri R, Guimarães J, Alves C, Chorão R, Lourenço E, Ribeiro P, Loureiro J L, Santos J V, Hamri A, Paternotte C, Hazan J, Silva M C, Prud'homme J F, Grid D
Department of Medicine, Hospital S. Sebastião, Santa Maria de Feira, Portugal.
Arch Neurol. 1999 Aug;56(8):943-9. doi: 10.1001/archneur.56.8.943.
Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive and predominant spasticity of the lower limbs, in which dominant, recessive, and X-linked forms have been described. While autosomal dominant HSP has been extensively studied, autosomal recessive HSP is less well known and is considered a rare condition.
To analyze the clinical presentation in a large group of patients with autosomal recessive HSP from Portugal and Algeria to define homogeneous groups that could serve as a guide for future molecular studies.
Clinical features in 106 patients belonging to 46 Portuguese and Algerian families with autosomal recessive HSP are presented, as well as the results of molecular studies in 23 of these families. Five phenotypes are defined: (1) pure early-onset families, (2) pure lateonset families, (3) complex families with mental retardation, (4) complex families with mental retardation and peripheral neuropathy, and (5) complex families with cerebellar ataxia. Six additional families have specific complex presentations, each of which is unique in the present series. Pyramidal signs in the upper limbs and pes cavus are frequent findings, while pseudobulbar signs, including dysarthria, dysphagia, and brisk jaw jerks, are more frequent in the complex forms. The complex forms have a poorer prognosis, while pure forms, particularly those with early onset, are more benign. One Algerian pure early-onset kindred was linked to the locus on chromosome 8, previously reported in 4 Tunisian families. Two of the Portuguese kindreds with complex forms (one with mental retardation and the other associated with hypoplasia of the corpus callosum) showed linkage to the locus recently identified on chromosome 16.
Although autosomal recessive HSP represents a heterogeneous group of diseases, some phenotypes can be defined by analyzing a large group of patients. The fact that only one Algerian family was linked to chromosome 8 suggests that this is a rare localization even in kindreds with the same ethnic background. Linkage to chromosome 16 was found in 2 clinically diverse Portuguese kindreds, illustrating that this locus is also rare and may correspond to different phenotypes.
遗传性痉挛性截瘫（HSPs）是一组异质性神经退行性疾病，其特征为下肢进行性且以痉挛为主，已描述有显性、隐性和X连锁形式。虽然常染色体显性HSP已得到广泛研究，但常染色体隐性HSP却鲜为人知，被认为是一种罕见病症。
分析来自葡萄牙和阿尔及利亚的一大组常染色体隐性HSP患者的临床表现，以确定可作为未来分子研究指南的同质组。
呈现了来自46个葡萄牙和阿尔及利亚常染色体隐性HSP家庭的106例患者的临床特征，以及其中23个家庭的分子研究结果。定义了五种表型：（1）单纯早发型家庭；（2）单纯晚发型家庭；（3）伴有智力障碍的复杂型家庭；（4）伴有智力障碍和周围神经病的复杂型家庭；（5）伴有小脑共济失调的复杂型家庭。另外六个家庭有特定的复杂表现，每个在本系列中都是独特的。上肢锥体束征和高弓足是常见表现，而包括构音障碍、吞咽困难和下颌快速反射在内的假性球麻痹征在复杂型中更常见。复杂型预后较差，而单纯型，尤其是早发型，病情更良性。一个阿尔及利亚单纯早发型家系与8号染色体上的位点连锁，此前在4个突尼斯家庭中有报道。两个具有复杂型的葡萄牙家系（一个伴有智力障碍，另一个伴有胼胝体发育不全）显示与最近在16号染色体上鉴定出的位点连锁。
虽然常染色体隐性HSP代表一组异质性疾病，但通过分析一大组患者可以定义一些表型。只有一个阿尔及利亚家庭与8号染色体连锁这一事实表明，即使在具有相同种族背景的家系中，这也是一个罕见的定位。在两个临床特征不同的葡萄牙家系中发现了与16号染色体的连锁，说明该位点也很罕见，可能对应不同的表型。
